GLEEVEC

29 min read

May 20, 2026

James Blackmer

Simple | Detailed

Quick Facts

Brand Name

GLEEVEC

Indication

Chronic Myeloid Leukemia (CML) – Newly Diagnosed

Key Contraindications

None.

Common Side Effects

preferred term (533%), fluid retention (0.9%), − superficial edema (0.4%), − other fluid retention reactions2 (0.6%)

How to Take

Take your prescribed dose by mouth with a meal and a large glass water.

Cost Plus Price

Cost Plus: $0.2728/pill

$0.27/fill

Chronic Myeloid Leukemia (CML) – Newly Diagnosed

Adults and children newly diagnosed with Ph+ chronic myeloid leukemia in early phase.

Chronic Myeloid Leukemia (CML) – Later Phases

Adults and children with Ph+ chronic myeloid leukemia in later phases, or in early phase after interferon therapy did not work.

Acute Lymphoblastic Leukemia (ALL) – Adults

Adults with Ph+ acute lymphoblastic leukemia that has come back or did not respond to prior treatment.

Acute Lymphoblastic Leukemia (ALL) – Children

Children newly diagnosed with Ph+ acute lymphoblastic leukemia, given with chemotherapy.

Myelodysplastic/Myeloproliferative Diseases (MDS/MPD)

Adults with certain rare blood disorders that involve changes in the PDGFR gene.

Aggressive Systemic Mastocytosis (ASM)

Adults with aggressive systemic mastocytosis without the D816V c-Kit mutation, or when the mutation status is not known.

Hypereosinophilic Syndrome (HES) and/or Chronic Eosinophilic Leukemia (CEL)

Adults with hypereosinophilic syndrome or chronic eosinophilic leukemia who have the FIP1L1-PDGFRα fusion gene, or for patients who do not have this gene or whose status is unknown.

Dermatofibrosarcoma Protuberans (DFSP)

Adults with a type of skin cancer that cannot be removed by surgery, has come back, or has spread to other parts of the body.

Gastrointestinal Stromal Tumors (GIST)

Patients with Kit (CD117) positive tumors of the stomach or intestines that cannot be removed by surgery, or have spread to other parts of the body.

Adjuvant Treatment of GIST

Adults who had a Kit (CD117) positive gastrointestinal stromal tumor completely removed by surgery, to help prevent it from coming back.

Chronic Myeloid Leukemia (CML) – Newly Diagnosed

Adults and children newly diagnosed with Ph+ chronic myeloid leukemia in early phase.

Chronic Myeloid Leukemia (CML) – Later Phases

Adults and children with Ph+ chronic myeloid leukemia in later phases, or in early phase after interferon therapy did not work.

Acute Lymphoblastic Leukemia (ALL) – Adults

Adults with Ph+ acute lymphoblastic leukemia that has come back or did not respond to prior treatment.

Acute Lymphoblastic Leukemia (ALL) – Children

Children newly diagnosed with Ph+ acute lymphoblastic leukemia, given with chemotherapy.

Myelodysplastic/Myeloproliferative Diseases (MDS/MPD)

Adults with certain rare blood disorders that involve changes in the PDGFR gene.

Aggressive Systemic Mastocytosis (ASM)

Adults with aggressive systemic mastocytosis without the D816V c-Kit mutation, or when the mutation status is not known.

Hypereosinophilic Syndrome (HES) and/or Chronic Eosinophilic Leukemia (CEL)

Adults with hypereosinophilic syndrome or chronic eosinophilic leukemia who have the FIP1L1-PDGFRα fusion gene, or for patients who do not have this gene or whose status is unknown.

Dermatofibrosarcoma Protuberans (DFSP)

Adults with a type of skin cancer that cannot be removed by surgery, has come back, or has spread to other parts of the body.

Gastrointestinal Stromal Tumors (GIST)

Patients with Kit (CD117) positive tumors of the stomach or intestines that cannot be removed by surgery, or have spread to other parts of the body.

Adjuvant Treatment of GIST

Adults who had a Kit (CD117) positive gastrointestinal stromal tumor completely removed by surgery, to help prevent it from coming back.

How to Take Your Medicine

Take your prescribed dose by mouth with a meal and a large glass water.

Doses of 400 mg or 600 mg: take once each day.
Dose of 800 mg: take 400 mg two times each day (once in the morning, once in the evening).

If You Cannot Swallow Pills

You can mix the tablet in water or apple juice. Put the tablet in about 50 mL (a small cup) of liquid for 100 mg tablets, or 200 mL (a large cup) for 400 mg tablets. Stir with a spoon. Drink it right after the tablet completely dissolves.

For daily doses of 800 mg or higher, use the 400 mg tablet to lower your iron exposure.

Keep taking this medicine as long as your doctor tells you to, as long as your disease does not get worse and you don’t have serious side effects.

Dose for Chronic Myeloid Leukemia (CML) – Adults

Chronic phase: 400 mg once daily
Accelerated phase or blast crisis: 600 mg once daily

Your doctor may increase your dose if your disease gets worse or if the medicine is not working well enough.

Dose for CML – Children

Children: 340 mg per square meter of body area each day, up to 600 mg maximum. Give as one dose daily or split into two doses.

Dose for Acute Lymphoblastic Leukemia (ALL) – Adults

600 mg once daily

Dose for ALL – Children

340 mg per square meter of body area each day, up to 600 mg maximum, together with chemotherapy.

Dose for MDS/MPD – Adults

400 mg once daily. Your doctor should test for PDGFRb gene changes first.

Dose for ASM – Adults

400 mg once daily, unless you have the D816V c-Kit mutation. Your doctor should test for this mutation first.

If you have ASM with eosinophilia (high eosinophil count): start with 100 mg once daily. Your doctor may increase this to 400 mg if needed.

Dose for HES/CEL – Adults

400 mg once daily. If you have the FIP1L1-PDGFRα fusion gene, start with 100 mg once daily. Your doctor may increase this to 400 mg if needed.

Dose for DFSP – Adults

800 mg each day (400 mg two times daily)

Dose for GIST (Tumor) – Adults

400 mg once daily. Your doctor may increase to 800 mg daily if your disease gets worse.

Dose After GIST Surgery – Adults

400 mg once daily. Studies looked at one year and three years of treatment. Three years is recommended for certain patients.

Changing Your Dose

If You Take Other Medicines

Some medicines can affect how Gleevec works. Tell your doctor about all medicines you take.

Liver Problems

Mild or moderate liver problems: no dose change needed.
Severe liver problems: your dose should be reduced by 25%.

Kidney Problems

Moderate kidney problems: cut your dose in half.
Mild kidney problems: do not take more than 600 mg.
Moderate kidney problems: do not take more than 400 mg.

Use with caution if you have severe kidney problems.

If You Have Liver Side Effects

If your liver tests get very high (bilirubin more than 3 times normal, or liver enzymes more than 5 times normal):
– Stop taking Gleevec until tests improve
– Start again at a lower dose (such as 400 mg to 300 mg, or 600 mg to 400 mg)

If You Have Blood Problems

If your white blood cells or platelets get very low, your doctor may stop or lower your dose. See the table below:

For most conditions:
– If white blood cells drop below 1.0 or platelets below 50: stop Gleevec until blood counts recover
– Then start again at your original dose
– If this happens again, lower your dose

For accelerated phase CML or ALL:
– If white blood cells drop below 0.5 or platelets below 10: your doctor will check if this is from leukemia
– If not from leukemia, lower your dose to 400 mg
– If still low after 2 weeks, lower to 300 mg
– If still low after 4 weeks, stop until counts recover, then restart at 300 mg

For DFSP:
– Stop until counts recover, then restart at 600 mg
– If it happens again, lower to 400 mg

Table 1: Dose Adjustments for Neutropenia and Thrombocytopenia
Abbreviations: ANC, absolute neutrophil count; ASM, aggressive systemic mastocytosis; CEL, chronic eosinophilic leukemia; CML, chronic myeloid leukemia; DFSP, dermatofibrosarcoma protuberans; HES, hypereosinophilic syndrome; MDS/MPD, myelodysplastic/myeloproliferative diseases; PDGFR, platelet-derived growth factor receptor; Ph+ CML, Philadelphia chromosome positive chronic myeloid leukemia; Ph+ ALL, Philadelphia chromosome positive acute lymphoblastic leukemia.
ASM associated with eosinophilia (starting dose 100 mg)	ANC less than 1 x 109/L and/or platelets less than 50 x 109/L	Stop Gleevec until ANC greater than or equal to 1.5 x 109/L and platelets greater than or equal to 75 x 109/L Resume treatment with Gleevec at previous dose (i.e., dose before severe adverse reaction)
HES/CEL with FIP1L1-PDGFRα fusion kinase (starting dose 100 mg)	ANC less than 1 x 109/L and/or platelets less than 50 x 109/L	Stop Gleevec until ANC greater than or equal to 1.5 x 109/L and platelets greater than or equal to 75 x 109/L Resume treatment with Gleevec at previous dose (i.e., dose before severe adverse reaction)
Chronic Phase CML (starting dose 400 mg) MDS/MPD, ASM and HES/CEL (starting dose 400 mg) GIST (starting dose 400 mg)	ANC less than 1 x 109/L and/or platelets less than 50 x 109/L	Stop Gleevec until ANC greater than or equal to 1.5 x 109/L and platelets greater than or equal to 75 x 109/L Resume treatment with Gleevec at the original starting dose of 400 mg If recurrence of ANC less than 1 x 109/L and/or platelets less than 50 x 109/L, repeat step 1 and resume Gleevec at a reduced dose of 300 mg


Ph+ CML: Accelerated Phase and Blast Crisis (starting dose 600 mg) Ph+ ALL (starting dose 600 mg)	ANC less than 0.5 x 109/L and/or platelets less than 10 x 109/L	Check if cytopenia is related to leukemia (marrow aspirate or biopsy) If cytopenia is unrelated to leukemia, reduce dose of Gleevec to 400 mg If cytopenia persists 2 weeks, reduce further to 300 mg If cytopenia persists 4 weeks and is still unrelated to leukemia, stop Gleevec until ANC greater than or equal to 1 x 109/L and platelets greater than or equal to 20 x 109/L and then resume treatment at 300 mg
DFSP (starting dose 800 mg)	ANC less than 1 x 109/L and/or platelets less than 50 x 109/L	Stop Gleevec until ANC greater than or equal to 1.5 x 109/L and platelets greater than or equal to 75 x 109/L Resume treatment with Gleevec at 600 mg In the event of recurrence of ANC less than 1 x 109/L and/or platelets less than 50 x 109/L, repeat step 1 and resume Gleevec at reduced dose of 400 mg
Pediatric newly diagnosed chronic phase CML (starting dose 340 mg/m2)	ANC less than 1 x 109/L and/or platelets less than 50 x 109/L	Stop Gleevec until ANC greater than or equal to 1.5 x 109/L and platelets greater than or equal to 75 x 109/L Resume treatment with Gleevec at previous dose (i.e., dose before severe adverse reaction) In the event of recurrence of ANC less than 1 x 109/L and/or platelets less than 50 x 109/L, repeat step 1 and resume Gleevec at reduced dose of 260 mg/m2

How to Take Your Medicine

Take your prescribed dose by mouth with a meal and a large glass water.

Doses of 400 mg or 600 mg: take once each day.

Dose of 800 mg: take 400 mg two times each day (once in the morning, once in the evening).

If You Cannot Swallow Pills

For daily doses of 800 mg or higher, use the 400 mg tablet to lower your iron exposure.

Keep taking this medicine as long as your doctor tells you to, as long as your disease does not get worse and you don’t have serious side effects.

Dose for Chronic Myeloid Leukemia (CML) – Adults

Chronic phase: 400 mg once daily

Accelerated phase or blast crisis: 600 mg once daily

Your doctor may increase your dose if your disease gets worse or if the medicine is not working well enough.

Dose for CML – Children

Children: 340 mg per square meter of body area each day, up to 600 mg maximum. Give as one dose daily or split into two doses.

Dose for Acute Lymphoblastic Leukemia (ALL) – Adults

600 mg once daily

Dose for ALL – Children

340 mg per square meter of body area each day, up to 600 mg maximum, together with chemotherapy.

Dose for MDS/MPD – Adults

400 mg once daily. Your doctor should test for PDGFRb gene changes first.

Dose for ASM – Adults

400 mg once daily, unless you have the D816V c-Kit mutation. Your doctor should test for this mutation first.

If you have ASM with eosinophilia (high eosinophil count): start with 100 mg once daily. Your doctor may increase this to 400 mg if needed.

Dose for HES/CEL – Adults

400 mg once daily. If you have the FIP1L1-PDGFRα fusion gene, start with 100 mg once daily. Your doctor may increase this to 400 mg if needed.

Dose for DFSP – Adults

800 mg each day (400 mg two times daily)

Dose for GIST (Tumor) – Adults

400 mg once daily. Your doctor may increase to 800 mg daily if your disease gets worse.

Dose After GIST Surgery – Adults

400 mg once daily. Studies looked at one year and three years of treatment. Three years is recommended for certain patients.

Changing Your Dose

If You Take Other Medicines

Some medicines can affect how Gleevec works. Tell your doctor about all medicines you take.

Liver Problems

Mild or moderate liver problems: no dose change needed.

Severe liver problems: your dose should be reduced by 25%.

Kidney Problems

Moderate kidney problems: cut your dose in half.

Mild kidney problems: do not take more than 600 mg.

Moderate kidney problems: do not take more than 400 mg.

Use with caution if you have severe kidney problems.

If You Have Liver Side Effects

If your liver tests get very high (bilirubin more than 3 times normal, or liver enzymes more than 5 times normal):

– Stop taking Gleevec until tests improve

– Start again at a lower dose (such as 400 mg to 300 mg, or 600 mg to 400 mg)

If You Have Blood Problems

If your white blood cells or platelets get very low, your doctor may stop or lower your dose. See the table below:

For most conditions:

– If white blood cells drop below 1.0 or platelets below 50: stop Gleevec until blood counts recover

– Then start again at your original dose

– If this happens again, lower your dose

For accelerated phase CML or ALL:

– If white blood cells drop below 0.5 or platelets below 10: your doctor will check if this is from leukemia

– If not from leukemia, lower your dose to 400 mg

– If still low after 2 weeks, lower to 300 mg

– If still low after 4 weeks, stop until counts recover, then restart at 300 mg

For DFSP:

– Stop until counts recover, then restart at 600 mg

– If it happens again, lower to 400 mg

Table 1: Dose Adjustments for Neutropenia and Thrombocytopenia
Abbreviations: ANC, absolute neutrophil count; ASM, aggressive systemic mastocytosis; CEL, chronic eosinophilic leukemia; CML, chronic myeloid leukemia; DFSP, dermatofibrosarcoma protuberans; HES, hypereosinophilic syndrome; MDS/MPD, myelodysplastic/myeloproliferative diseases; PDGFR, platelet-derived growth factor receptor; Ph+ CML, Philadelphia chromosome positive chronic myeloid leukemia; Ph+ ALL, Philadelphia chromosome positive acute lymphoblastic leukemia.
ASM associated with eosinophilia (starting dose 100 mg)	ANC less than 1 x 109/L and/or platelets less than 50 x 109/L	Stop Gleevec until ANC greater than or equal to 1.5 x 109/L and platelets greater than or equal to 75 x 109/L Resume treatment with Gleevec at previous dose (i.e., dose before severe adverse reaction)
HES/CEL with FIP1L1-PDGFRα fusion kinase (starting dose 100 mg)	ANC less than 1 x 109/L and/or platelets less than 50 x 109/L	Stop Gleevec until ANC greater than or equal to 1.5 x 109/L and platelets greater than or equal to 75 x 109/L Resume treatment with Gleevec at previous dose (i.e., dose before severe adverse reaction)
Chronic Phase CML (starting dose 400 mg) MDS/MPD, ASM and HES/CEL (starting dose 400 mg) GIST (starting dose 400 mg)	ANC less than 1 x 109/L and/or platelets less than 50 x 109/L	Stop Gleevec until ANC greater than or equal to 1.5 x 109/L and platelets greater than or equal to 75 x 109/L Resume treatment with Gleevec at the original starting dose of 400 mg If recurrence of ANC less than 1 x 109/L and/or platelets less than 50 x 109/L, repeat step 1 and resume Gleevec at a reduced dose of 300 mg


Ph+ CML: Accelerated Phase and Blast Crisis (starting dose 600 mg) Ph+ ALL (starting dose 600 mg)	ANC less than 0.5 x 109/L and/or platelets less than 10 x 109/L	Check if cytopenia is related to leukemia (marrow aspirate or biopsy) If cytopenia is unrelated to leukemia, reduce dose of Gleevec to 400 mg If cytopenia persists 2 weeks, reduce further to 300 mg If cytopenia persists 4 weeks and is still unrelated to leukemia, stop Gleevec until ANC greater than or equal to 1 x 109/L and platelets greater than or equal to 20 x 109/L and then resume treatment at 300 mg
DFSP (starting dose 800 mg)	ANC less than 1 x 109/L and/or platelets less than 50 x 109/L	Stop Gleevec until ANC greater than or equal to 1.5 x 109/L and platelets greater than or equal to 75 x 109/L Resume treatment with Gleevec at 600 mg In the event of recurrence of ANC less than 1 x 109/L and/or platelets less than 50 x 109/L, repeat step 1 and resume Gleevec at reduced dose of 400 mg
Pediatric newly diagnosed chronic phase CML (starting dose 340 mg/m2)	ANC less than 1 x 109/L and/or platelets less than 50 x 109/L	Stop Gleevec until ANC greater than or equal to 1.5 x 109/L and platelets greater than or equal to 75 x 109/L Resume treatment with Gleevec at previous dose (i.e., dose before severe adverse reaction) In the event of recurrence of ANC less than 1 x 109/L and/or platelets less than 50 x 109/L, repeat step 1 and resume Gleevec at reduced dose of 260 mg/m2

100 mg Tablets

Very dark yellow to brownish orange, film-coated tablets. Round shape with beveled edges. Marked “NVR” on one side and “SA” on the other side with a score line.

400 mg Tablets

Very dark yellow to brownish orange, film-coated tablets. Oval shape with beveled edges. Marked “gleevec” on one side and a score line on the other. Also marked “400” with “SL” on each side of the score line.

100 mg Tablets

Very dark yellow to brownish orange, film-coated tablets. Round shape with beveled edges. Marked “NVR” on one side and “SA” on the other side with a score line.

400 mg Tablets

None.

Fluid Retention and Swelling

Gleevec often causes swelling (edema). Your doctor will check your weight regularly. Tell your doctor right away if you gain weight quickly. Swelling is more common with higher doses and in patients over 65 years old.

Low Blood Counts

Gleevec can lower your blood counts. This includes red blood cells (anemia), white blood cells (neutropenia), and platelets (thrombocytopenia). You will need blood tests weekly for the first month, then every 2 weeks for the second month, and then regularly after that.

Heart Problems

Gleevec can cause heart failure. This is more common in older patients or those with heart disease. Tell your doctor if you have chest pain, shortness of breath, or leg swelling.

Liver Problems

Gleevec can cause liver damage, sometimes severe. Liver failure has been reported. Your doctor will do blood tests to check your liver before treatment and regularly during treatment.

Bleeding

Gleevec can cause bleeding. This was reported in about 2% of CML patients and 13% of GIST patients.

Stomach and Intestinal Problems

Gleevec can irritate your stomach. Take it with food and a full glass of water. Rare cases of stomach or intestinal tears have been reported, including some that were fatal.

Heart Problems in Patients with High Eosinophil Levels

Patients with high eosinophil levels may develop heart problems when starting Gleevec. Your doctor may check your heart and may give you steroids to prevent problems.

Skin Reactions

Gleevec can cause serious skin reactions. These include erythema multiforme and Stevens-Johnson syndrome. Tell your doctor right away if you get a rash, blisters, or mouth sores.

Low Thyroid Hormone

Gleevec can lower thyroid hormone levels. Patients on thyroid medicine may need their dose adjusted. Your doctor will check your thyroid levels.

Pregnancy Warning

Gleevec can harm an unborn baby. Women who can get pregnant should use birth control during treatment and for 14 days after stopping Gleevec. Tell your doctor right away if you become pregnant.

Growth Effects in Children

Gleevec may slow growth in children. Your doctor will monitor your child’s growth during treatment.

Tumor Lysis Syndrome

Gleevec can cause tumor lysis syndrome (TLS). This is a serious condition that can happen when cancer cells break down quickly. Your doctor will monitor you for this, especially if you have a large tumor. Drink plenty of fluids.

Driving and Using Machines

Gleevec may cause dizziness, blurred vision, or drowsiness. Be careful when driving or using machines. Do not drive if you feel dizzy or tired.

Kidney Problems

Gleevec may cause kidney problems. Your doctor will check your kidney function before and during treatment. This is especially important if you already have kidney disease, diabetes, high blood pressure, or heart failure.

Fluid Retention and Swelling

Low Blood Counts

Heart Problems

Gleevec can cause heart failure. This is more common in older patients or those with heart disease. Tell your doctor if you have chest pain, shortness of breath, or leg swelling.

Liver Problems

Gleevec can cause liver damage, sometimes severe. Liver failure has been reported. Your doctor will do blood tests to check your liver before treatment and regularly during treatment.

Bleeding

Gleevec can cause bleeding. This was reported in about 2% of CML patients and 13% of GIST patients.

Stomach and Intestinal Problems

Gleevec can irritate your stomach. Take it with food and a full glass of water. Rare cases of stomach or intestinal tears have been reported, including some that were fatal.

Heart Problems in Patients with High Eosinophil Levels

Patients with high eosinophil levels may develop heart problems when starting Gleevec. Your doctor may check your heart and may give you steroids to prevent problems.

Skin Reactions

Gleevec can cause serious skin reactions. These include erythema multiforme and Stevens-Johnson syndrome. Tell your doctor right away if you get a rash, blisters, or mouth sores.

Low Thyroid Hormone

Gleevec can lower thyroid hormone levels. Patients on thyroid medicine may need their dose adjusted. Your doctor will check your thyroid levels.

Pregnancy Warning

Gleevec can harm an unborn baby. Women who can get pregnant should use birth control during treatment and for 14 days after stopping Gleevec. Tell your doctor right away if you become pregnant.

Growth Effects in Children

Gleevec may slow growth in children. Your doctor will monitor your child’s growth during treatment.

Tumor Lysis Syndrome

Driving and Using Machines

Gleevec may cause dizziness, blurred vision, or drowsiness. Be careful when driving or using machines. Do not drive if you feel dizzy or tired.

Kidney Problems

Serious Side Effects

This drug has caused serious side effects. These include heart problems, liver problems, bleeding, fluid retention, and blood problems. Your doctor will watch you for these.

Common Side Effects

Most patients taking this medicine had side effects. The most common were:
– Swelling (edema)
– Nausea and vomiting
– Muscle cramps
– Muscle or bone pain
– Diarrhea
– Rash
– Tiredness
– Headache

Swelling was common. It often happened around the eyes or in the legs. Sometimes this swelling was serious. Your doctor may need to lower your dose or stop the medicine.

Blood Problems

This medicine can cause low blood counts. You may have:
– Low white blood cells (neutropenia)
– Low platelets (thrombocytopenia)
– Low red blood cells (anemia)

Your blood will be checked often. If counts get too low, your doctor may pause treatment or lower the dose.

Other Side Effects

Other side effects included:
– Stomach pain
– Joint pain
– Dizziness
– Fever
– Weight gain
– Trouble sleeping
– Cough
– Constipation

In Children

Children had similar side effects as adults. Most common were nausea, vomiting, and low blood counts.

Side Effects That May Be Serious

Some side effects can be serious. Call your doctor right away if you have:
– Unusual bleeding or bruising
– Yellow skin or eyes
– Chest pain
– Trouble breathing
– Severe stomach pain
– Fever or infection
– Swelling that gets worse

Lab Tests

Your blood will be checked regularly. This medicine can affect:
– Liver tests
– Blood cell counts
– Kidney function

When to Call Your Doctor

Tell your doctor right away if you have:
– Signs of infection (fever, chills, sore throat)
– Unusual bleeding or bruising
– Swelling in your legs or around your eyes
– Yellow skin or eyes
– Nausea that doesn’t stop
– Extreme tiredness
– Muscle weakness or cramps that are bad

Table 2: Adverse Reactions Regardless of Relationship to Study Drug Reported in Newly Diagnosed CML Clinical Trial in the Gleevec Versus IFN+Ara-C Study (Greater Than or Equal to 10% of Gleevec-Treated Patients)(1)
Abbreviations: CML, chronic myeloid leukemia; CNS, central nervous system; CTC, common terminology criteria; GI, gastrointestinal; IFN, Interferon-alpha. *NCI Common Terminology Criteria for Adverse Events, version 3.0. (1)All adverse reactions occurring in greater than or equal to 10% of Gleevec-treated patients are listed regardless of suspected relationship to treatment. (2)Other fluid retention reactions include pleural effusion, ascites, pulmonary edema, pericardial effusion, anasarca, edema aggravated, and fluid retention not otherwise specified.
	All Grades		CTC Grades* 3/4
	Gleevec	IFN+Ara−C	Gleevec	IFN+Ara−C
Preferred term	N = 551 (%)	N = 533 (%)	N = 551 (%)	N = 533 (%)
Fluid retention	61.7	11.1	2.5	0.9
− Superficial edema	59.9	9.6	1.5	0.4
− Other fluid retention reactions2	6.9	1.9	1.3	0.6
Nausea	49.5	61.5	1.3	5.1
Muscle cramps	49.2	11.8	2.2	0.2
Musculoskeletal pain	47.0	44.8	5.4	8.6
Diarrhea	45.4	43.3	3.3	3.2
Rash and related terms	40.1	26.1	2.9	2.4
Fatigue	38.8	67.0	1.8	25.1
Headache	37.0	43.3	0.5	3.8
Joint pain	31.4	38.1	2.5	7.7
Abdominal pain	36.5	25.9	4.2	3.9
Nasopharyngitis	30.5	8.8	0	0.4
Hemorrhage	28.9	21.2	1.8	1.7
– GI hemorrhage	1.6	1.1	0.5	0.2
– CNS hemorrhage	0.2	0.4	0	0.4
Myalgia	24.1	38.8	1.5	8.3
Vomiting	22.5	27.8	2.0	3.4
Dyspepsia	18.9	8.3	0	0.8
Cough	20.0	23.1	0.2	0.6
Pharyngolaryngeal pain	18.1	11.4	0.2	0
Upper respiratory tract infection	21.2	8.4	0.2	0.4
Dizziness	19.4	24.4	0.9	3.8
Pyrexia	17.8	42.6	0.9	3.0
Weight increased	15.6	2.6	2.0	0.4
Insomnia	14.7	18.6	0	2.3
Depression	14.9	35.8	0.5	13.1
Influenza	13.8	6.2	0.2	0.2
Bone pain	11.3	15.6	1.6	3.4
Constipation	11.4	14.4	0.7	0.2
Sinusitis	11.4	6.0	0.2	0.2

Table 3: Most Frequently Reported Non-Hematologic Adverse Reactions (regardless of relationship to study drug) in Patients With Newly Diagnosed Ph+ CML-CP in the Gleevec Versus Nilotinib Study (Greater Than or Equal to 10% in Gleevec 400 mg Once Daily or Nilotinib 300 mg Twice Daily Groups) 60-Month Analysisa
Abbreviation: Ph+ CML-CP, Philadelphia chromosome positive chronic myeloid leukemia-chronic phase. aExcluding laboratory abnormalities. bNCI Common Terminology Criteria for Adverse Events, version 3.0.
		Patients with newly diagnosed Ph+ CML-CP

		Gleevec 400 mg once daily	Nilotinib 300 mg twice daily	Gleevec 400 mg once daily	Nilotinib 300 mg twice daily
		N = 280	N = 279	N = 280	N = 279
Body system and preferred term		All Grades (%)		CTC Gradesb 3/4 (%)
Skin and subcutaneous tissue disorders	Rash	19	38	2	< 1
	Pruritus	7	21	0	< 1
	Alopecia	7	13	0	0
	Dry skin	6	12	0	0
Gastrointestinal disorders	Nausea	41	22	2	2
	Constipation	8	20	0	< 1
	Diarrhea	46	19	4	1
	Vomiting	27	15	< 1	< 1
	Abdominal pain upper	14	18	< 1	1
	Abdominal pain	12	15	0	2
	Dyspepsia	12	10	0	0
Nervous system disorders	Headache	23	32	< 1	3
	Dizziness	11	12	< 1	< 1
General disorders and administration-site conditions	Fatigue	20	23	1	1
	Pyrexia	13	14	0	< 1
	Asthenia	12	14	0	< 1
	Peripheral edema	20	9	0	< 1
	Face edema	14	< 1	< 1	0
Musculoskeletal and connective tissue disorders	Myalgia	19	19	< 1	< 1
	Arthralgia	17	22	< 1	< 1
	Muscle spasms	34	12	1	0
	Pain in extremity	16	15	< 1	< 1
	Back pain	17	19	1	1
Respiratory, thoracic and mediastinal disorders	Cough	13	17	0	0
	Oropharyngeal pain	6	12	0	0
	Dyspnea	6	11	< 1	2
Infections and infestations	Nasopharyngitis	21	27	0	0
	Upper respiratory tract infection	14	17	0	< 1
	Influenza	9	13	0	0
	Gastroenteritis	10	7	< 1	0
Eye disorders	Eyelid edema	19	1	< 1	0
	Periorbital edema	15	< 1	0	0
Psychiatric disorders	Insomnia	9	11	0	0
Vascular disorder	Hypertension	4	10	< 1	1

Table 4: Adverse Reactions Regardless of Relationship to Study Drug Reported in Other CML Clinical Trials (Greater Than or Equal to 10% of All Patients in Any Trial)(1)
Abbreviations: CML, chronic myeloid leukemia; IFN, Interferon-alpha. (1)All adverse reactions occurring in greater than or equal to 10% of patients are listed regardless of suspected relationship to treatment. (2)Other fluid retention reactions include pleural effusion, ascites, pulmonary edema, pericardial effusion, anasarca, edema aggravated, and fluid retention not otherwise specified.
	Myeloid blast Crisis (n = 260)		Accelerated phase (n = 235)		Chronic phase, IFN failure (n = 532)
	%		%		%
Preferred term	All Grades	Grade 3/4	All Grades	Grade 3/4	All Grades	Grade 3/4
Fluid retention	72	11	76	6	69	4
-Superficial edema	66	6	74	3	67	2
-Other fluid retention reactions(2)	22	6	15	4	7	2
Nausea	71	5	73	5	63	3
Muscle cramps	28	1	47	0.4	62	2
Vomiting	54	4	58	3	36	2
Diarrhea	43	4	57	5	48	3
Hemorrhage	53	19	49	11	30	2
– CNS hemorrhage	9	7	3	3	2	1
– GI hemorrhage	8	4	6	5	2	0.4
Musculoskeletal pain	42	9	49	9	38	2
Fatigue	30	4	46	4	48	1
Skin rash	36	5	47	5	47	3
Pyrexia	41	7	41	8	21	2
Arthralgia	25	5	34	6	40	1
Headache	27	5	32	2	36	0.6
Abdominal pain	30	6	33	4	32	1
Weight increased	5	1	17	5	32	7
Cough	14	0.8	27	0.9	20	0
Dyspepsia	12	0	22	0	27	0
Myalgia	9	0	24	2	27	0.2
Nasopharyngitis	10	0	17	0	22	0.2
Asthenia	18	5	21	5	15	0.2
Dyspnea	15	4	21	7	12	0.9
Upper respiratory tract infection	3	0	12	0.4	19	0
Anorexia	14	2	17	2	7	0
Night sweats	13	0.8	17	1	14	0.2
Constipation	16	2	16	0.9	9	0.4
Dizziness	12	0.4	13	0	16	0.2
Pharyngitis	10	0	12	0	15	0
Insomnia	10	0	14	0	14	0.2
Pruritus	8	1	14	0.9	14	0.8
Hypokalemia	13	4	9	2	6	0.8
Pneumonia	13	7	10	7	4	1
Anxiety	8	0.8	12	0	8	0.4
Liver toxicity	10	5	12	6	6	3
Rigors	10	0	12	0.4	10	0
Chest pain	7	2	10	0.4	11	0.8
Influenza	0.8	0.4	6	0	11	0.2
Sinusitis	4	0.4	11	0.4	9	0.4

Table 5: Laboratory Abnormalities in Newly Diagnosed CML Clinical Trial (Gleevec Versus IFN+Ara-C)
Abbreviations: CML, chronic myeloid leukemia; IFN, Interferon-alpha; SGOT, serum glutamic-oxaloacetic transaminase is now referred to as aspartate aminotransferase (AST); SGPT, serum glutamic-pyruvic transaminase is now referred to as alanine aminotransferase (ALT). *p less than 0.001 (difference in Grade 3 plus 4 abnormalities between the two treatment groups).
	Gleevec N = 551		IFN+Ara−C N = 533
	%		%
CTC Grades	Grade 3	Grade 4	Grade 3	Grade 4
Hematology parameters*
− Neutropenia*	13.1	3.6	20.8	4.5
− Thrombocytopenia*	8.5	0.4	15.9	0.6
− Anemia	3.3	1.1	4.1	0.2
Biochemistry parameters
− Elevated creatinine	0	0	0.4	0
− Elevated bilirubin	0.9	0.2	0.2	0
− Elevated alkaline phosphatase	0.2	0	0.8	0
− Elevated SGOT (AST)/SGPT (ALT)	4.7	0.5	7.1	0.4

Table 6: Percent Incidence of Clinically Relevant Grade 3/4* Laboratory Abnormalities in the Newly Diagnosed CML Clinical Trial (Gleevec Versus Nilotinib)
Abbreviations: CML, chronic myeloid leukemia; SGOT, serum glutamic-oxaloacetic transaminase is now referred to as aspartate aminotransferase (AST); SGPT, serum glutamic-pyruvic transaminase is now referred to as alanine aminotransferase (ALT). *NCI Common Terminology Criteria for Adverse Events, version 3.0.
	Gleevec 400 mg once daily N = 280 (%)	Nilotinib 300 mg twice daily N = 279 (%)
Hematologic parameters
Thrombocytopenia	9	10
Neutropenia	22	12
Anemia	6	4
Biochemistry parameters
Elevated lipase	4	9
Hyperglycemia	< 1	7
Hypophosphatemia	10	8
Elevated bilirubin (total)	< 1	4
Elevated SGPT (ALT)	3	4
Hyperkalemia	1	2
Hyponatremia	< 1	1
Hypokalemia	2	< 1
Elevated SGOT (AST)	1	1
Decreased albumin	< 1	0
Hypocalcemia	< 1	< 1
Elevated alkaline phosphatase	< 1	0
Elevated creatinine	< 1	0

Table 7: Laboratory Abnormalities in Other CML Clinical Trials
Abbreviations: CML, chronic myeloid leukemia; CTC, common terminology criteria; IFN, Interferon-alpha; SGOT, serum glutamic-oxaloacetic transaminase is now referred to as aspartate aminotransferase (AST); SGPT, serum glutamic-pyruvic transaminase is now referred to as alanine aminotransferase (ALT). (1)CTC Grades: neutropenia (Grade 3 greater than or equal to 0.5–1.0 x 109/L, Grade 4 less than 0.5 x 109/L), thrombocytopenia (Grade 3 greater than or equal to 10–50 x 109/L, Grade 4 less than 10 x 109/L), anemia (hemoglobin greater than or equal to 65–80 g/L, Grade 4 less than 65 g/L), elevated creatinine (Grade 3 greater than 3–6 x upper limit normal range [ULN], Grade 4 greater than 6 x ULN), elevated bilirubin (Grade 3 greater than 3–10 x ULN, Grade 4 greater than 10 x ULN), elevated alkaline phosphatase (Grade 3 greater than 5–20 x ULN, Grade 4 greater than 20 x ULN), elevated SGOT or SGPT (Grade 3 greater than 5–20 x ULN, Grade 4 greater than 20 x ULN).
	Myeloid blast crisis (n = 260)		Accelerated phase (n = 235)		Chronic phase, IFN failure (n = 532)
	600 mg n = 223 400 mg n = 37		600 mg n = 158 400 mg n = 77		400 mg
	%		%		%
CTC Grades(1)	Grade 3	Grade 4	Grade 3	Grade 4	Grade 3	Grade 4
Hematology parameters
− Neutropenia	16	48	23	36	27	9
− Thrombocytopenia	30	33	31	13	21	< 1
− Anemia	42	11	34	7	6	1
Biochemistry parameters
− Elevated creatinine	1.5	0	1.3	0	0.2	0
− Elevated bilirubin	3.8	0	2.1	0	0.6	0
− Elevated alkaline phosphatase	4.6	0	5.5	0.4	0.2	0
− Elevated SGOT (AST)	1.9	0	3.0	0	2.3	0
− Elevated SGPT (ALT)	2.3	0.4	4.3	0	2.1	0

Table 8: Adverse Reactions Reported More Frequently in Patients Treated With Study Drug (Greater Than 5%) or in Cycles With Study Drug (Greater Than 1%)
Abbreviations: Ph+ ALL, Philadelphia chromosome positive acute lymphoblastic leukemia; Ph- ALL, Philadelphia chromosome negative acute lymphoblastic leukemia. Defined as the frequency of adverse events (AEs) per patient per treatment cycles that included Gleevec (includes patients with Ph+ ALL that received cycles with Gleevec). *Defined as the frequency of AEs per patient per treatment cycles that did not include Gleevec (includes patients with Ph+ ALL that received cycles without Gleevec as well as all patients with Ph- ALL who did not receive Gleevec in any treatment cycle).
Adverse event	Per patient incidence Ph+ ALL with gleevec N = 92 n (%)	Per patient incidence Ph- ALL no gleevec N = 65 n (%)	Per patient per cycle incidence with gleevec* N = 778 n (%)	Per patient per cycle incidence no gleevec** N = 647 n (%)
Grade 3 and 4 adverse events
Nausea and/or vomiting	15 (16)	6 (9)	28 (4)	8 (1)
Hypokalemia	31 (34)	16 (25)	72 (9)	32 (5)
Pneumonitis	7 (8)	1 (1)	7 (1)	1 (< 1)
Pleural effusion	6 (7)	0	6 (1)	0
Abdominal pain	8 (9)	2 (3)	9 (1)	3 (< 1)
Anorexia	10 (11)	3 (5)	19 (2)	4 (1)
Hemorrhage	11 (12)	4 (6)	17 (2)	8 (1)
Hypoxia	8 (9)	2 (3)	12 (2)	2 (< 1)
Myalgia	5 (5)	0	4 (1)	1 (< 1)
Stomatitis	15 (16)	8 (12)	22 (3)	14 (2)
Diarrhea	8 (9)	3 (5)	12 (2)	3 (< 1)
Rash/Skin disorder	4 (4)	0	5 (1)	0
Infection	49 (53)	32 (49)	131 (17)	92 (14)
Hepatic (transaminase and/or bilirubin)	52 (57)	38 (58)	172 (22)	113 (17)
Hypotension	10 (11)	5 (8)	16 (2)	6 (1)
Myelosuppression
Neutropenia (< 750/mcL)	92 (100)	63 (97)	556 (71)	218 (34)
Thrombocytopenia (< 75,000/mcL)	90 (92)	63 (97)	431 (55)	329 (51)

Table 9: Adverse Reactions Regardless of Relationship to Study Drug Reported (More Than One Patient) in MPD Patients in the Phase 2 Study (Greater Than or Equal to 10% All Patients) All Grades
Abbreviation: MPD, myeloproliferative disease.
Preferred term	N = 7 n (%)
Nausea	4 (57.1)
Diarrhea	3 (42.9)
Anemia	2 (28.6)
Fatigue	2 (28.6)
Muscle cramp	3 (42.9)
Arthralgia	2 (28.6)
Periorbital edema	2 (28.6)

Table 10: Adverse Reactions Regardless of Relationship to Study Drug Reported in DFSP Patients in the Phase 2 Study (Greater Than or Equal to 10% All Patients) All Grades
Abbreviation: DFSP, dermatofibrosarcoma protuberans.
Preferred term	N = 12 n (%)
Nausea	5 (41.7)
Diarrhea	3 (25.0)
Vomiting	3 (25.0)
Periorbital edema	4 (33.3)
Face edema	2 (16.7)
Rash	3 (25.0)
Fatigue	5 (41.7)
Peripheral edema	4 (33.3)
Pyrexia	2 (16.7)
Eye edema	4 (33.3)
Lacrimation increased	3 (25.0)
Dyspnea exertional	2 (16.7)
Anemia	3 (25.0)
Rhinitis	2 (16.7)
Anorexia	2 (16.7)

Table 11: Laboratory Abnormalities Reported in DFSP Patients in the Phase 2 Study
Abbreviation: CTC, common terminology criteria. (1)CTC Grades: neutropenia (Grade 3 greater than or equal to 0.5–1.0 x 109/L, Grade 4 less than 0.5 x 109/L), thrombocytopenia (Grade 3 greater than or equal to 10–50 x 109/L, Grade 4 less than 10 x 109/L), anemia (Grade 3 greater than or equal to 65–80 g/L, Grade 4 less than 65 g/L), elevated creatinine (Grade 3 greater than 3–6 x upper limit normal range [ULN], Grade 4 greater than 6 x ULN).
	N = 12
CTC Grades(1)	Grade 3 %	Grade 4 %
Hematology parameters
– Anemia	17	0
– Thrombocytopenia	17	0
– Neutropenia	0	8
Biochemistry parameters
– Elevated creatinine	0	8

Table 12: Number (%) of Patients With Adverse Reactions Regardless of Relationship to Study Drug Where Frequency is Greater Than or Equal to 10% in any One Group (Full Analysis Set) in the Phase 3 Unresectable and/or Malignant Metastatic GIST Clinical Trials
Abbreviations: ANC, absolute neutrophil count; GI, gastrointestinal; GIST, gastrointestinal stromal tumors.
Reported or specified term	Imatinib 400 mg N = 818		Imatinib 800 mg N = 822
	All Grades %	Grades 3/4/5 %	All Grades %	Grades 3/4/5 %
Edema	76.7	9.0	86.1	13.1
Fatigue/lethargy, malaise, asthenia	69.3	11.7	74.9	12.2
Nausea	58.1	9.0	64.5	7.8
Abdominal pain/cramping	57.2	13.8	55.2	11.8
Diarrhea	56.2	8.1	58.2	8.6
Rash/desquamation	38.1	7.6	49.8	8.9
Vomiting	37.4	9.2	40.6	7.5
Myalgia	32.2	5.6	30.2	3.8
Anemia	32.0	4.9	34.8	6.4
Anorexia	31.1	6.6	35.8	4.7
Other GI toxicity	25.2	8.1	28.1	6.6
Headache	22.0	5.7	19.7	3.6
Other pain (excluding tumor related pain)	20.4	5.9	20.8	5.0
Other dermatology/skin toxicity	17.6	5.9	20.1	5.7
Leukopenia	17.0	0.7	19.6	1.6
Other constitutional symptoms	16.7	6.4	15.2	4.4
Cough	16.1	4.5	14.5	3.2
Infection (without neutropenia)	15.5	6.6	16.5	5.6
Pruritus	15.4	5.4	18.9	4.3
Other neurological toxicity	15.0	6.4	15.2	4.9
Constipation	14.8	5.1	14.4	4.1
Other renal/genitourinary toxicity	14.2	6.5	13.6	5.2
Arthralgia (joint pain)	13.6	4.8	12.3	3.0
Dyspnea (shortness of breath)	13.6	6.8	14.2	5.6
Fever in absence of neutropenia (ANC < 1.0 x 109/L)	13.2	4.9	12.9	3.4
Sweating	12.7	4.6	8.5	2.8
Other hemorrhage	12.3	6.7	13.3	6.1
Weight gain	12.0	1.0	10.6	0.6
Alopecia	11.9	4.3	14.8	3.2
Dyspepsia/heartburn	11.5	0.6	10.9	0.5
Neutropenia/granulocytopenia	11.5	3.1	16.1	4.1
Rigors/chills	11.0	4.6	10.2	3.0
Dizziness/lightheadedness	11.0	4.8	10.0	2.8
Creatinine increase	10.8	0.4	10.1	0.6
Flatulence	10.0	0.2	10.1	0.1
Stomatitis/pharyngitis (oral/pharyngeal mucositis)	9.2	5.4	10.0	4.3
Lymphopenia	6.0	0.7	10.1	1.9

Table 13: Laboratory Abnormalities in the Phase 2 Unresectable and/or Malignant Metastatic GIST Trial
Abbreviations: CTC, common terminology criteria; GIST, gastrointestinal stromal tumors; SGOT, serum glutamic-oxaloacetic transaminase is now referred to as aspartate aminotransferase (AST); SGPT, serum glutamic-pyruvic transaminase is now referred to as alanine aminotransferase (ALT). 1CTC Grades: neutropenia (Grade 3 greater than or equal to 0.5–1.0 x 109/L, Grade 4 less than 0.5 x 109/L), thrombocytopenia (Grade 3 greater than or equal to 10–50 x 109/L, Grade 4 less than 10 x 109/L), anemia (Grade 3 greater than or equal to 65–80 g/L, Grade 4 less than 65 g/L), elevated creatinine (Grade 3 greater than 3–6 x upper limit normal range [ULN], Grade 4 greater than 6 x ULN), elevated bilirubin (Grade 3 greater than 3–10 x ULN, Grade 4 greater than 10 x ULN), elevated alkaline phosphatase, SGOT or SGPT (Grade 3 greater than 5–20 x ULN, Grade 4 greater than 20 x ULN), albumin (Grade 3 less than 20 g/L).
	400 mg (n = 73)		600 mg (n = 74)
	%		%
CTC Grades1	Grade 3	Grade 4	Grade 3	Grade 4
Hematology parameters
− Anemia	3	0	8	1
− Thrombocytopenia	0	0	1	0
− Neutropenia	7	3	8	3
Biochemistry parameters
− Elevated creatinine	0	0	3	0
− Reduced albumin	3	0	4	0
− Elevated bilirubin	1	0	1	3
− Elevated alkaline phosphatase	0	0	3	0
− Elevated SGOT (AST)	4	0	3	3
− Elevated SGPT (ALT)	6	0	7	1

Table 14: Adverse Reactions Regardless of Relationship to Study Drug Reported in Study 1 (Greater Than or Equal to 5% of Gleevec-Treated Patients)(1)
Abbreviations: CTC, common terminology criteria; GIST, gastrointestinal stromal tumors; SGOT, serum glutamic-oxaloacetic transaminase is now referred to as aspartate aminotransferase (AST); SGPT, serum glutamic-pyruvic transaminase is now referred to as alanine aminotransferase (ALT). *NCI Common Terminology Criteria for Adverse Events, version 3.0. (1)All adverse reactions occurring in greater than or equal to 5% of patients are listed regardless of suspected relationship to treatment. A patient with multiple occurrences of an adverse reaction is counted only once in the adverse reaction category.
	All CTC Grades		CTC Grade 3* and Above
	Gleevec (n = 337)	Placebo (n = 345)	Gleevec (n = 337)	Placebo (n = 345)
Preferred term	%	%	%	%
Diarrhea	59.3	29.3	3.0	1.4
Fatigue	57.0	40.9	2.1	1.2
Nausea	53.1	27.8	2.4	1.2
Periorbital edema	47.2	14.5	1.2	0
Hemoglobin decreased	46.9	27.0	0.6	0
Peripheral edema	26.7	14.8	0.3	0
Rash (Exfoliative)	26.1	12.8	2.7	0
Vomiting	25.5	13.9	2.4	0.6
Abdominal pain	21.1	22.3	3.0	1.4
Headache	19.3	20.3	0.6	0
Dyspepsia	17.2	13.0	0.9	0
Anorexia	16.9	8.7	0.3	0
Weight increased	16.9	11.6	0.3	0
Liver enzymes (ALT) increased	16.6	13.0	2.7	0
Muscle spasms	16.3	3.3	0	0
Neutrophil count decreased	16.0	6.1	3.3	0.9
Arthralgia	15.1	14.5	0	0.3
White blood cell count decreased	14.5	4.3	0.6	0.3
Constipation	12.8	17.7	0	0.3
Dizziness	12.5	10.7	0	0.3
Liver enzymes (AST) increased	12.2	7.5	2.1	0
Myalgia	12.2	11.6	0	0.3
Blood creatinine increased	11.6	5.8	0	0.3
Cough	11.0	11.3	0	0
Pruritus	11.0	7.8	0.9	0
Weight decreased	10.1	5.2	0	0
Hyperglycemia	9.8	11.3	0.6	1.7
Insomnia	9.8	7.2	0.9	0
Lacrimation increased	9.8	3.8	0	0
Alopecia	9.5	6.7	0	0
Flatulence	8.9	9.6	0	0
Rash	8.9	5.2	0.9	0
Abdominal distension	7.4	6.4	0.3	0.3
Back pain	7.4	8.1	0.6	0
Pain in extremity	7.4	7.2	0.3	0
Hypokalemia	7.1	2.0	0.9	0.6
Depression	6.8	6.4	0.9	0.6
Facial edema	6.8	1.2	0.3	0
Blood alkaline phosphatase increased	6.5	7.5	0	0
Dry skin	6.5	5.2	0	0
Dysgeusia	6.5	2.9	0	0
Abdominal pain upper	6.2	6.4	0.3	0
Neuropathy peripheral	5.9	6.4	0	0
Hypocalcemia	5.6	1.7	0.3	0
Leukopenia	5.0	2.6	0.3	0
Platelet count decreased	5.0	3.5	0	0
Stomatitis	5.0	1.7	0.6	0
Upper respiratory tract infection	5.0	3.5	0	0
Vision blurred	5.0	2.3	0	0

Table 15: Adverse Reactions Regardless of Relationship to Study Drug by Preferred Term All Grades and 3/4 Grades (Greater Than or Equal to 5% of Gleevec-Treated Patients) Study 2(1)
Abbreviations: AE, adverse event; CTC, common terminology criteria. (1)All adverse reactions occurring in greater than or equal to 5% of patients are listed regardless of suspected relationship to treatment. A patient with multiple occurrences of an adverse reaction is counted only once in the adverse reaction category.
Preferred term	All CTC Grades		CTC Grades 3 and above
	Gleevec 12 Months (N = 194) %	Gleevec 36 Months (N = 198) %	Gleevec 12 Months (N = 194) %	Gleevec 36 Months (N = 198) %
Patients with at least one AE	99.0	100.0	20.1	32.8
Hemoglobin decreased	72.2	80.3	0.5	0.5
Periorbital edema	59.3	74.2	0.5	1.0
Blood lactate dehydrogenase increased	43.3	60.1	0	0
Diarrhea	43.8	54.0	0.5	2.0
Nausea	44.8	51.0	1.5	0.5
Muscle spasms	30.9	49.0	0.5	1.0
Fatigue	48.5	48.5	1.0	0.5
White blood cell count decreased	34.5	47.0	2.1	3.0
Pain	25.8	45.5	1.0	3.0
Blood creatinine increased	30.4	44.4	0	0
Peripheral edema	33.0	40.9	0.5	1.0
Dermatitis	29.4	38.9	2.1	1.5
Aspartate aminotransferase increased	30.9	37.9	1.5	3.0
Alanine aminotransferase increased	28.9	34.3	2.1	3.0
Neutrophil count decreased	24.2	33.3	4.6	5.1
Hypoproteinemia	23.7	31.8	0	0
Infection	13.9	27.8	1.5	2.5
Weight increased	13.4	26.8	0	0.5
Pruritus	12.9	25.8	0	0
Flatulence	19.1	24.7	1.0	0.5
Vomiting	10.8	22.2	0.5	1.0
Dyspepsia	17.5	21.7	0.5	1.0
Hypoalbuminemia	11.9	21.2	0	0
Edema	10.8	19.7	0	0.5
Abdominal distension	11.9	19.2	0.5	0
Headache	8.2	18.2	0	0
Lacrimation increased	18.0	17.7	0	0
Arthralgia	8.8	17.2	0	1.0
Blood alkaline phosphatase increased	10.8	16.7	0	0.5
Dyspnea	6.2	16.2	0.5	1.5
Myalgia	9.3	15.2	0	1.0
Platelet count decreased	11.3	14.1	0	0
Blood bilirubin increased	11.3	13.1	0	0
Dysgeusia	9.3	12.6	0	0
Paresthesia	5.2	12.1	0	0.5
Vision blurred	10.8	11.1	1.0	0.5
Alopecia	11.3	10.6	0	0
Decreased appetite	9.8	10.1	0	0
Constipation	8.8	9.6	0	0
Pyrexia	6.2	9.6	0	0
Depression	3.1	8.1	0	0
Abdominal pain	2.6	7.6	0	0
Conjunctivitis	5.2	7.6	0	0
Photosensitivity reaction	3.6	7.1	0	0
Dizziness	4.6	6.6	0.5	0
Hemorrhage	3.1	6.6	0	0
Dry skin	6.7	6.1	0.5	0
Nasopharyngitis	1.0	6.1	0	0.5
Palpitations	5.2	5.1	0	0

Serious Side Effects

This drug has caused serious side effects. These include heart problems, liver problems, bleeding, fluid retention, and blood problems. Your doctor will watch you for these.

Common Side Effects

Most patients taking this medicine had side effects. The most common were:

– Swelling (edema)

– Nausea and vomiting

– Muscle cramps

– Muscle or bone pain

– Diarrhea

– Rash

– Tiredness

– Headache

Swelling was common. It often happened around the eyes or in the legs. Sometimes this swelling was serious. Your doctor may need to lower your dose or stop the medicine.

Blood Problems

This medicine can cause low blood counts. You may have:

– Low white blood cells (neutropenia)

– Low platelets (thrombocytopenia)

– Low red blood cells (anemia)

Your blood will be checked often. If counts get too low, your doctor may pause treatment or lower the dose.

Other Side Effects

Other side effects included:

– Stomach pain

– Joint pain

– Dizziness

– Fever

– Weight gain

– Trouble sleeping

– Cough

– Constipation

In Children

Children had similar side effects as adults. Most common were nausea, vomiting, and low blood counts.

Side Effects That May Be Serious

Some side effects can be serious. Call your doctor right away if you have:

– Unusual bleeding or bruising

– Yellow skin or eyes

– Chest pain

– Trouble breathing

– Severe stomach pain

– Fever or infection

– Swelling that gets worse

Lab Tests

Your blood will be checked regularly. This medicine can affect:

– Liver tests

– Blood cell counts

– Kidney function

When to Call Your Doctor

Tell your doctor right away if you have:

– Signs of infection (fever, chills, sore throat)

– Unusual bleeding or bruising

– Swelling in your legs or around your eyes

– Yellow skin or eyes

– Nausea that doesn’t stop

– Extreme tiredness

– Muscle weakness or cramps that are bad

Table 2: Adverse Reactions Regardless of Relationship to Study Drug Reported in Newly Diagnosed CML Clinical Trial in the Gleevec Versus IFN+Ara-C Study (Greater Than or Equal to 10% of Gleevec-Treated Patients)(1)
Abbreviations: CML, chronic myeloid leukemia; CNS, central nervous system; CTC, common terminology criteria; GI, gastrointestinal; IFN, Interferon-alpha. *NCI Common Terminology Criteria for Adverse Events, version 3.0. (1)All adverse reactions occurring in greater than or equal to 10% of Gleevec-treated patients are listed regardless of suspected relationship to treatment. (2)Other fluid retention reactions include pleural effusion, ascites, pulmonary edema, pericardial effusion, anasarca, edema aggravated, and fluid retention not otherwise specified.
	All Grades		CTC Grades* 3/4
	Gleevec	IFN+Ara−C	Gleevec	IFN+Ara−C
Preferred term	N = 551 (%)	N = 533 (%)	N = 551 (%)	N = 533 (%)
Fluid retention	61.7	11.1	2.5	0.9
− Superficial edema	59.9	9.6	1.5	0.4
− Other fluid retention reactions2	6.9	1.9	1.3	0.6
Nausea	49.5	61.5	1.3	5.1
Muscle cramps	49.2	11.8	2.2	0.2
Musculoskeletal pain	47.0	44.8	5.4	8.6
Diarrhea	45.4	43.3	3.3	3.2
Rash and related terms	40.1	26.1	2.9	2.4
Fatigue	38.8	67.0	1.8	25.1
Headache	37.0	43.3	0.5	3.8
Joint pain	31.4	38.1	2.5	7.7
Abdominal pain	36.5	25.9	4.2	3.9
Nasopharyngitis	30.5	8.8	0	0.4
Hemorrhage	28.9	21.2	1.8	1.7
– GI hemorrhage	1.6	1.1	0.5	0.2
– CNS hemorrhage	0.2	0.4	0	0.4
Myalgia	24.1	38.8	1.5	8.3
Vomiting	22.5	27.8	2.0	3.4
Dyspepsia	18.9	8.3	0	0.8
Cough	20.0	23.1	0.2	0.6
Pharyngolaryngeal pain	18.1	11.4	0.2	0
Upper respiratory tract infection	21.2	8.4	0.2	0.4
Dizziness	19.4	24.4	0.9	3.8
Pyrexia	17.8	42.6	0.9	3.0
Weight increased	15.6	2.6	2.0	0.4
Insomnia	14.7	18.6	0	2.3
Depression	14.9	35.8	0.5	13.1
Influenza	13.8	6.2	0.2	0.2
Bone pain	11.3	15.6	1.6	3.4
Constipation	11.4	14.4	0.7	0.2
Sinusitis	11.4	6.0	0.2	0.2

Table 3: Most Frequently Reported Non-Hematologic Adverse Reactions (regardless of relationship to study drug) in Patients With Newly Diagnosed Ph+ CML-CP in the Gleevec Versus Nilotinib Study (Greater Than or Equal to 10% in Gleevec 400 mg Once Daily or Nilotinib 300 mg Twice Daily Groups) 60-Month Analysisa
Abbreviation: Ph+ CML-CP, Philadelphia chromosome positive chronic myeloid leukemia-chronic phase. aExcluding laboratory abnormalities. bNCI Common Terminology Criteria for Adverse Events, version 3.0.
		Patients with newly diagnosed Ph+ CML-CP

		Gleevec 400 mg once daily	Nilotinib 300 mg twice daily	Gleevec 400 mg once daily	Nilotinib 300 mg twice daily
		N = 280	N = 279	N = 280	N = 279
Body system and preferred term		All Grades (%)		CTC Gradesb 3/4 (%)
Skin and subcutaneous tissue disorders	Rash	19	38	2	< 1
	Pruritus	7	21	0	< 1
	Alopecia	7	13	0	0
	Dry skin	6	12	0	0
Gastrointestinal disorders	Nausea	41	22	2	2
	Constipation	8	20	0	< 1
	Diarrhea	46	19	4	1
	Vomiting	27	15	< 1	< 1
	Abdominal pain upper	14	18	< 1	1
	Abdominal pain	12	15	0	2
	Dyspepsia	12	10	0	0
Nervous system disorders	Headache	23	32	< 1	3
	Dizziness	11	12	< 1	< 1
General disorders and administration-site conditions	Fatigue	20	23	1	1
	Pyrexia	13	14	0	< 1
	Asthenia	12	14	0	< 1
	Peripheral edema	20	9	0	< 1
	Face edema	14	< 1	< 1	0
Musculoskeletal and connective tissue disorders	Myalgia	19	19	< 1	< 1
	Arthralgia	17	22	< 1	< 1
	Muscle spasms	34	12	1	0
	Pain in extremity	16	15	< 1	< 1
	Back pain	17	19	1	1
Respiratory, thoracic and mediastinal disorders	Cough	13	17	0	0
	Oropharyngeal pain	6	12	0	0
	Dyspnea	6	11	< 1	2
Infections and infestations	Nasopharyngitis	21	27	0	0
	Upper respiratory tract infection	14	17	0	< 1
	Influenza	9	13	0	0
	Gastroenteritis	10	7	< 1	0
Eye disorders	Eyelid edema	19	1	< 1	0
	Periorbital edema	15	< 1	0	0
Psychiatric disorders	Insomnia	9	11	0	0
Vascular disorder	Hypertension	4	10	< 1	1

Table 4: Adverse Reactions Regardless of Relationship to Study Drug Reported in Other CML Clinical Trials (Greater Than or Equal to 10% of All Patients in Any Trial)(1)
Abbreviations: CML, chronic myeloid leukemia; IFN, Interferon-alpha. (1)All adverse reactions occurring in greater than or equal to 10% of patients are listed regardless of suspected relationship to treatment. (2)Other fluid retention reactions include pleural effusion, ascites, pulmonary edema, pericardial effusion, anasarca, edema aggravated, and fluid retention not otherwise specified.
	Myeloid blast Crisis (n = 260)		Accelerated phase (n = 235)		Chronic phase, IFN failure (n = 532)
	%		%		%
Preferred term	All Grades	Grade 3/4	All Grades	Grade 3/4	All Grades	Grade 3/4
Fluid retention	72	11	76	6	69	4
-Superficial edema	66	6	74	3	67	2
-Other fluid retention reactions(2)	22	6	15	4	7	2
Nausea	71	5	73	5	63	3
Muscle cramps	28	1	47	0.4	62	2
Vomiting	54	4	58	3	36	2
Diarrhea	43	4	57	5	48	3
Hemorrhage	53	19	49	11	30	2
– CNS hemorrhage	9	7	3	3	2	1
– GI hemorrhage	8	4	6	5	2	0.4
Musculoskeletal pain	42	9	49	9	38	2
Fatigue	30	4	46	4	48	1
Skin rash	36	5	47	5	47	3
Pyrexia	41	7	41	8	21	2
Arthralgia	25	5	34	6	40	1
Headache	27	5	32	2	36	0.6
Abdominal pain	30	6	33	4	32	1
Weight increased	5	1	17	5	32	7
Cough	14	0.8	27	0.9	20	0
Dyspepsia	12	0	22	0	27	0
Myalgia	9	0	24	2	27	0.2
Nasopharyngitis	10	0	17	0	22	0.2
Asthenia	18	5	21	5	15	0.2
Dyspnea	15	4	21	7	12	0.9
Upper respiratory tract infection	3	0	12	0.4	19	0
Anorexia	14	2	17	2	7	0
Night sweats	13	0.8	17	1	14	0.2
Constipation	16	2	16	0.9	9	0.4
Dizziness	12	0.4	13	0	16	0.2
Pharyngitis	10	0	12	0	15	0
Insomnia	10	0	14	0	14	0.2
Pruritus	8	1	14	0.9	14	0.8
Hypokalemia	13	4	9	2	6	0.8
Pneumonia	13	7	10	7	4	1
Anxiety	8	0.8	12	0	8	0.4
Liver toxicity	10	5	12	6	6	3
Rigors	10	0	12	0.4	10	0
Chest pain	7	2	10	0.4	11	0.8
Influenza	0.8	0.4	6	0	11	0.2
Sinusitis	4	0.4	11	0.4	9	0.4

Table 5: Laboratory Abnormalities in Newly Diagnosed CML Clinical Trial (Gleevec Versus IFN+Ara-C)
Abbreviations: CML, chronic myeloid leukemia; IFN, Interferon-alpha; SGOT, serum glutamic-oxaloacetic transaminase is now referred to as aspartate aminotransferase (AST); SGPT, serum glutamic-pyruvic transaminase is now referred to as alanine aminotransferase (ALT). *p less than 0.001 (difference in Grade 3 plus 4 abnormalities between the two treatment groups).
	Gleevec N = 551		IFN+Ara−C N = 533
	%		%
CTC Grades	Grade 3	Grade 4	Grade 3	Grade 4
Hematology parameters*
− Neutropenia*	13.1	3.6	20.8	4.5
− Thrombocytopenia*	8.5	0.4	15.9	0.6
− Anemia	3.3	1.1	4.1	0.2
Biochemistry parameters
− Elevated creatinine	0	0	0.4	0
− Elevated bilirubin	0.9	0.2	0.2	0
− Elevated alkaline phosphatase	0.2	0	0.8	0
− Elevated SGOT (AST)/SGPT (ALT)	4.7	0.5	7.1	0.4

Table 6: Percent Incidence of Clinically Relevant Grade 3/4* Laboratory Abnormalities in the Newly Diagnosed CML Clinical Trial (Gleevec Versus Nilotinib)
Abbreviations: CML, chronic myeloid leukemia; SGOT, serum glutamic-oxaloacetic transaminase is now referred to as aspartate aminotransferase (AST); SGPT, serum glutamic-pyruvic transaminase is now referred to as alanine aminotransferase (ALT). *NCI Common Terminology Criteria for Adverse Events, version 3.0.
	Gleevec 400 mg once daily N = 280 (%)	Nilotinib 300 mg twice daily N = 279 (%)
Hematologic parameters
Thrombocytopenia	9	10
Neutropenia	22	12
Anemia	6	4
Biochemistry parameters
Elevated lipase	4	9
Hyperglycemia	< 1	7
Hypophosphatemia	10	8
Elevated bilirubin (total)	< 1	4
Elevated SGPT (ALT)	3	4
Hyperkalemia	1	2
Hyponatremia	< 1	1
Hypokalemia	2	< 1
Elevated SGOT (AST)	1	1
Decreased albumin	< 1	0
Hypocalcemia	< 1	< 1
Elevated alkaline phosphatase	< 1	0
Elevated creatinine	< 1	0

Table 7: Laboratory Abnormalities in Other CML Clinical Trials
Abbreviations: CML, chronic myeloid leukemia; CTC, common terminology criteria; IFN, Interferon-alpha; SGOT, serum glutamic-oxaloacetic transaminase is now referred to as aspartate aminotransferase (AST); SGPT, serum glutamic-pyruvic transaminase is now referred to as alanine aminotransferase (ALT). (1)CTC Grades: neutropenia (Grade 3 greater than or equal to 0.5–1.0 x 109/L, Grade 4 less than 0.5 x 109/L), thrombocytopenia (Grade 3 greater than or equal to 10–50 x 109/L, Grade 4 less than 10 x 109/L), anemia (hemoglobin greater than or equal to 65–80 g/L, Grade 4 less than 65 g/L), elevated creatinine (Grade 3 greater than 3–6 x upper limit normal range [ULN], Grade 4 greater than 6 x ULN), elevated bilirubin (Grade 3 greater than 3–10 x ULN, Grade 4 greater than 10 x ULN), elevated alkaline phosphatase (Grade 3 greater than 5–20 x ULN, Grade 4 greater than 20 x ULN), elevated SGOT or SGPT (Grade 3 greater than 5–20 x ULN, Grade 4 greater than 20 x ULN).
	Myeloid blast crisis (n = 260)		Accelerated phase (n = 235)		Chronic phase, IFN failure (n = 532)
	600 mg n = 223 400 mg n = 37		600 mg n = 158 400 mg n = 77		400 mg
	%		%		%
CTC Grades(1)	Grade 3	Grade 4	Grade 3	Grade 4	Grade 3	Grade 4
Hematology parameters
− Neutropenia	16	48	23	36	27	9
− Thrombocytopenia	30	33	31	13	21	< 1
− Anemia	42	11	34	7	6	1
Biochemistry parameters
− Elevated creatinine	1.5	0	1.3	0	0.2	0
− Elevated bilirubin	3.8	0	2.1	0	0.6	0
− Elevated alkaline phosphatase	4.6	0	5.5	0.4	0.2	0
− Elevated SGOT (AST)	1.9	0	3.0	0	2.3	0
− Elevated SGPT (ALT)	2.3	0.4	4.3	0	2.1	0

Table 8: Adverse Reactions Reported More Frequently in Patients Treated With Study Drug (Greater Than 5%) or in Cycles With Study Drug (Greater Than 1%)
Abbreviations: Ph+ ALL, Philadelphia chromosome positive acute lymphoblastic leukemia; Ph- ALL, Philadelphia chromosome negative acute lymphoblastic leukemia. Defined as the frequency of adverse events (AEs) per patient per treatment cycles that included Gleevec (includes patients with Ph+ ALL that received cycles with Gleevec). *Defined as the frequency of AEs per patient per treatment cycles that did not include Gleevec (includes patients with Ph+ ALL that received cycles without Gleevec as well as all patients with Ph- ALL who did not receive Gleevec in any treatment cycle).
Adverse event	Per patient incidence Ph+ ALL with gleevec N = 92 n (%)	Per patient incidence Ph- ALL no gleevec N = 65 n (%)	Per patient per cycle incidence with gleevec* N = 778 n (%)	Per patient per cycle incidence no gleevec** N = 647 n (%)
Grade 3 and 4 adverse events
Nausea and/or vomiting	15 (16)	6 (9)	28 (4)	8 (1)
Hypokalemia	31 (34)	16 (25)	72 (9)	32 (5)
Pneumonitis	7 (8)	1 (1)	7 (1)	1 (< 1)
Pleural effusion	6 (7)	0	6 (1)	0
Abdominal pain	8 (9)	2 (3)	9 (1)	3 (< 1)
Anorexia	10 (11)	3 (5)	19 (2)	4 (1)
Hemorrhage	11 (12)	4 (6)	17 (2)	8 (1)
Hypoxia	8 (9)	2 (3)	12 (2)	2 (< 1)
Myalgia	5 (5)	0	4 (1)	1 (< 1)
Stomatitis	15 (16)	8 (12)	22 (3)	14 (2)
Diarrhea	8 (9)	3 (5)	12 (2)	3 (< 1)
Rash/Skin disorder	4 (4)	0	5 (1)	0
Infection	49 (53)	32 (49)	131 (17)	92 (14)
Hepatic (transaminase and/or bilirubin)	52 (57)	38 (58)	172 (22)	113 (17)
Hypotension	10 (11)	5 (8)	16 (2)	6 (1)
Myelosuppression
Neutropenia (< 750/mcL)	92 (100)	63 (97)	556 (71)	218 (34)
Thrombocytopenia (< 75,000/mcL)	90 (92)	63 (97)	431 (55)	329 (51)

Table 9: Adverse Reactions Regardless of Relationship to Study Drug Reported (More Than One Patient) in MPD Patients in the Phase 2 Study (Greater Than or Equal to 10% All Patients) All Grades
Abbreviation: MPD, myeloproliferative disease.
Preferred term	N = 7 n (%)
Nausea	4 (57.1)
Diarrhea	3 (42.9)
Anemia	2 (28.6)
Fatigue	2 (28.6)
Muscle cramp	3 (42.9)
Arthralgia	2 (28.6)
Periorbital edema	2 (28.6)

Table 10: Adverse Reactions Regardless of Relationship to Study Drug Reported in DFSP Patients in the Phase 2 Study (Greater Than or Equal to 10% All Patients) All Grades
Abbreviation: DFSP, dermatofibrosarcoma protuberans.
Preferred term	N = 12 n (%)
Nausea	5 (41.7)
Diarrhea	3 (25.0)
Vomiting	3 (25.0)
Periorbital edema	4 (33.3)
Face edema	2 (16.7)
Rash	3 (25.0)
Fatigue	5 (41.7)
Peripheral edema	4 (33.3)
Pyrexia	2 (16.7)
Eye edema	4 (33.3)
Lacrimation increased	3 (25.0)
Dyspnea exertional	2 (16.7)
Anemia	3 (25.0)
Rhinitis	2 (16.7)
Anorexia	2 (16.7)

Table 11: Laboratory Abnormalities Reported in DFSP Patients in the Phase 2 Study
Abbreviation: CTC, common terminology criteria. (1)CTC Grades: neutropenia (Grade 3 greater than or equal to 0.5–1.0 x 109/L, Grade 4 less than 0.5 x 109/L), thrombocytopenia (Grade 3 greater than or equal to 10–50 x 109/L, Grade 4 less than 10 x 109/L), anemia (Grade 3 greater than or equal to 65–80 g/L, Grade 4 less than 65 g/L), elevated creatinine (Grade 3 greater than 3–6 x upper limit normal range [ULN], Grade 4 greater than 6 x ULN).
	N = 12
CTC Grades(1)	Grade 3 %	Grade 4 %
Hematology parameters
– Anemia	17	0
– Thrombocytopenia	17	0
– Neutropenia	0	8
Biochemistry parameters
– Elevated creatinine	0	8

Table 12: Number (%) of Patients With Adverse Reactions Regardless of Relationship to Study Drug Where Frequency is Greater Than or Equal to 10% in any One Group (Full Analysis Set) in the Phase 3 Unresectable and/or Malignant Metastatic GIST Clinical Trials
Abbreviations: ANC, absolute neutrophil count; GI, gastrointestinal; GIST, gastrointestinal stromal tumors.
Reported or specified term	Imatinib 400 mg N = 818		Imatinib 800 mg N = 822
	All Grades %	Grades 3/4/5 %	All Grades %	Grades 3/4/5 %
Edema	76.7	9.0	86.1	13.1
Fatigue/lethargy, malaise, asthenia	69.3	11.7	74.9	12.2
Nausea	58.1	9.0	64.5	7.8
Abdominal pain/cramping	57.2	13.8	55.2	11.8
Diarrhea	56.2	8.1	58.2	8.6
Rash/desquamation	38.1	7.6	49.8	8.9
Vomiting	37.4	9.2	40.6	7.5
Myalgia	32.2	5.6	30.2	3.8
Anemia	32.0	4.9	34.8	6.4
Anorexia	31.1	6.6	35.8	4.7
Other GI toxicity	25.2	8.1	28.1	6.6
Headache	22.0	5.7	19.7	3.6
Other pain (excluding tumor related pain)	20.4	5.9	20.8	5.0
Other dermatology/skin toxicity	17.6	5.9	20.1	5.7
Leukopenia	17.0	0.7	19.6	1.6
Other constitutional symptoms	16.7	6.4	15.2	4.4
Cough	16.1	4.5	14.5	3.2
Infection (without neutropenia)	15.5	6.6	16.5	5.6
Pruritus	15.4	5.4	18.9	4.3
Other neurological toxicity	15.0	6.4	15.2	4.9
Constipation	14.8	5.1	14.4	4.1
Other renal/genitourinary toxicity	14.2	6.5	13.6	5.2
Arthralgia (joint pain)	13.6	4.8	12.3	3.0
Dyspnea (shortness of breath)	13.6	6.8	14.2	5.6
Fever in absence of neutropenia (ANC < 1.0 x 109/L)	13.2	4.9	12.9	3.4
Sweating	12.7	4.6	8.5	2.8
Other hemorrhage	12.3	6.7	13.3	6.1
Weight gain	12.0	1.0	10.6	0.6
Alopecia	11.9	4.3	14.8	3.2
Dyspepsia/heartburn	11.5	0.6	10.9	0.5
Neutropenia/granulocytopenia	11.5	3.1	16.1	4.1
Rigors/chills	11.0	4.6	10.2	3.0
Dizziness/lightheadedness	11.0	4.8	10.0	2.8
Creatinine increase	10.8	0.4	10.1	0.6
Flatulence	10.0	0.2	10.1	0.1
Stomatitis/pharyngitis (oral/pharyngeal mucositis)	9.2	5.4	10.0	4.3
Lymphopenia	6.0	0.7	10.1	1.9

Table 13: Laboratory Abnormalities in the Phase 2 Unresectable and/or Malignant Metastatic GIST Trial
Abbreviations: CTC, common terminology criteria; GIST, gastrointestinal stromal tumors; SGOT, serum glutamic-oxaloacetic transaminase is now referred to as aspartate aminotransferase (AST); SGPT, serum glutamic-pyruvic transaminase is now referred to as alanine aminotransferase (ALT). 1CTC Grades: neutropenia (Grade 3 greater than or equal to 0.5–1.0 x 109/L, Grade 4 less than 0.5 x 109/L), thrombocytopenia (Grade 3 greater than or equal to 10–50 x 109/L, Grade 4 less than 10 x 109/L), anemia (Grade 3 greater than or equal to 65–80 g/L, Grade 4 less than 65 g/L), elevated creatinine (Grade 3 greater than 3–6 x upper limit normal range [ULN], Grade 4 greater than 6 x ULN), elevated bilirubin (Grade 3 greater than 3–10 x ULN, Grade 4 greater than 10 x ULN), elevated alkaline phosphatase, SGOT or SGPT (Grade 3 greater than 5–20 x ULN, Grade 4 greater than 20 x ULN), albumin (Grade 3 less than 20 g/L).
	400 mg (n = 73)		600 mg (n = 74)
	%		%
CTC Grades1	Grade 3	Grade 4	Grade 3	Grade 4
Hematology parameters
− Anemia	3	0	8	1
− Thrombocytopenia	0	0	1	0
− Neutropenia	7	3	8	3
Biochemistry parameters
− Elevated creatinine	0	0	3	0
− Reduced albumin	3	0	4	0
− Elevated bilirubin	1	0	1	3
− Elevated alkaline phosphatase	0	0	3	0
− Elevated SGOT (AST)	4	0	3	3
− Elevated SGPT (ALT)	6	0	7	1

Table 14: Adverse Reactions Regardless of Relationship to Study Drug Reported in Study 1 (Greater Than or Equal to 5% of Gleevec-Treated Patients)(1)
Abbreviations: CTC, common terminology criteria; GIST, gastrointestinal stromal tumors; SGOT, serum glutamic-oxaloacetic transaminase is now referred to as aspartate aminotransferase (AST); SGPT, serum glutamic-pyruvic transaminase is now referred to as alanine aminotransferase (ALT). *NCI Common Terminology Criteria for Adverse Events, version 3.0. (1)All adverse reactions occurring in greater than or equal to 5% of patients are listed regardless of suspected relationship to treatment. A patient with multiple occurrences of an adverse reaction is counted only once in the adverse reaction category.
	All CTC Grades		CTC Grade 3* and Above
	Gleevec (n = 337)	Placebo (n = 345)	Gleevec (n = 337)	Placebo (n = 345)
Preferred term	%	%	%	%
Diarrhea	59.3	29.3	3.0	1.4
Fatigue	57.0	40.9	2.1	1.2
Nausea	53.1	27.8	2.4	1.2
Periorbital edema	47.2	14.5	1.2	0
Hemoglobin decreased	46.9	27.0	0.6	0
Peripheral edema	26.7	14.8	0.3	0
Rash (Exfoliative)	26.1	12.8	2.7	0
Vomiting	25.5	13.9	2.4	0.6
Abdominal pain	21.1	22.3	3.0	1.4
Headache	19.3	20.3	0.6	0
Dyspepsia	17.2	13.0	0.9	0
Anorexia	16.9	8.7	0.3	0
Weight increased	16.9	11.6	0.3	0
Liver enzymes (ALT) increased	16.6	13.0	2.7	0
Muscle spasms	16.3	3.3	0	0
Neutrophil count decreased	16.0	6.1	3.3	0.9
Arthralgia	15.1	14.5	0	0.3
White blood cell count decreased	14.5	4.3	0.6	0.3
Constipation	12.8	17.7	0	0.3
Dizziness	12.5	10.7	0	0.3
Liver enzymes (AST) increased	12.2	7.5	2.1	0
Myalgia	12.2	11.6	0	0.3
Blood creatinine increased	11.6	5.8	0	0.3
Cough	11.0	11.3	0	0
Pruritus	11.0	7.8	0.9	0
Weight decreased	10.1	5.2	0	0
Hyperglycemia	9.8	11.3	0.6	1.7
Insomnia	9.8	7.2	0.9	0
Lacrimation increased	9.8	3.8	0	0
Alopecia	9.5	6.7	0	0
Flatulence	8.9	9.6	0	0
Rash	8.9	5.2	0.9	0
Abdominal distension	7.4	6.4	0.3	0.3
Back pain	7.4	8.1	0.6	0
Pain in extremity	7.4	7.2	0.3	0
Hypokalemia	7.1	2.0	0.9	0.6
Depression	6.8	6.4	0.9	0.6
Facial edema	6.8	1.2	0.3	0
Blood alkaline phosphatase increased	6.5	7.5	0	0
Dry skin	6.5	5.2	0	0
Dysgeusia	6.5	2.9	0	0
Abdominal pain upper	6.2	6.4	0.3	0
Neuropathy peripheral	5.9	6.4	0	0
Hypocalcemia	5.6	1.7	0.3	0
Leukopenia	5.0	2.6	0.3	0
Platelet count decreased	5.0	3.5	0	0
Stomatitis	5.0	1.7	0.6	0
Upper respiratory tract infection	5.0	3.5	0	0
Vision blurred	5.0	2.3	0	0

Table 15: Adverse Reactions Regardless of Relationship to Study Drug by Preferred Term All Grades and 3/4 Grades (Greater Than or Equal to 5% of Gleevec-Treated Patients) Study 2(1)
Abbreviations: AE, adverse event; CTC, common terminology criteria. (1)All adverse reactions occurring in greater than or equal to 5% of patients are listed regardless of suspected relationship to treatment. A patient with multiple occurrences of an adverse reaction is counted only once in the adverse reaction category.
Preferred term	All CTC Grades		CTC Grades 3 and above
	Gleevec 12 Months (N = 194) %	Gleevec 36 Months (N = 198) %	Gleevec 12 Months (N = 194) %	Gleevec 36 Months (N = 198) %
Patients with at least one AE	99.0	100.0	20.1	32.8
Hemoglobin decreased	72.2	80.3	0.5	0.5
Periorbital edema	59.3	74.2	0.5	1.0
Blood lactate dehydrogenase increased	43.3	60.1	0	0
Diarrhea	43.8	54.0	0.5	2.0
Nausea	44.8	51.0	1.5	0.5
Muscle spasms	30.9	49.0	0.5	1.0
Fatigue	48.5	48.5	1.0	0.5
White blood cell count decreased	34.5	47.0	2.1	3.0
Pain	25.8	45.5	1.0	3.0
Blood creatinine increased	30.4	44.4	0	0
Peripheral edema	33.0	40.9	0.5	1.0
Dermatitis	29.4	38.9	2.1	1.5
Aspartate aminotransferase increased	30.9	37.9	1.5	3.0
Alanine aminotransferase increased	28.9	34.3	2.1	3.0
Neutrophil count decreased	24.2	33.3	4.6	5.1
Hypoproteinemia	23.7	31.8	0	0
Infection	13.9	27.8	1.5	2.5
Weight increased	13.4	26.8	0	0.5
Pruritus	12.9	25.8	0	0
Flatulence	19.1	24.7	1.0	0.5
Vomiting	10.8	22.2	0.5	1.0
Dyspepsia	17.5	21.7	0.5	1.0
Hypoalbuminemia	11.9	21.2	0	0
Edema	10.8	19.7	0	0.5
Abdominal distension	11.9	19.2	0.5	0
Headache	8.2	18.2	0	0
Lacrimation increased	18.0	17.7	0	0
Arthralgia	8.8	17.2	0	1.0
Blood alkaline phosphatase increased	10.8	16.7	0	0.5
Dyspnea	6.2	16.2	0.5	1.5
Myalgia	9.3	15.2	0	1.0
Platelet count decreased	11.3	14.1	0	0
Blood bilirubin increased	11.3	13.1	0	0
Dysgeusia	9.3	12.6	0	0
Paresthesia	5.2	12.1	0	0.5
Vision blurred	10.8	11.1	1.0	0.5
Alopecia	11.3	10.6	0	0
Decreased appetite	9.8	10.1	0	0
Constipation	8.8	9.6	0	0
Pyrexia	6.2	9.6	0	0
Depression	3.1	8.1	0	0
Abdominal pain	2.6	7.6	0	0
Conjunctivitis	5.2	7.6	0	0
Photosensitivity reaction	3.6	7.1	0	0
Dizziness	4.6	6.6	0.5	0
Hemorrhage	3.1	6.6	0	0
Dry skin	6.7	6.1	0.5	0
Nasopharyngitis	1.0	6.1	0	0.5
Palpitations	5.2	5.1	0	0

Drugs That Lower Gleevec Levels

Some drugs can make Gleevec work less well. Your doctor may need to change your medicines.

Drugs That Raise Gleevec Levels

Some drugs can make Gleevec levels too high. Do not drink grapefruit juice while taking Gleevec.

Drugs Processed by CYP3A4

Gleevec can raise levels of other drugs your body processes through CYP3A4. These include:

– Certain anxiety medicines
– Certain blood pressure medicines
– Certain cholesterol medicines

Use caution with these drugs if they need exact dosing. Tell your doctor about all medicines you take.

Blood Thinners (Warfarin)

Warfarin is processed by CYP3A4. Use heparin instead of warfarin for blood thinning if needed.

Drugs Processed by CYP2D6

Use caution with CYP2D6 drugs that need exact dosing. Tell your doctor about all medicines you take.

Methotrexate

Gleevec may raise methotrexate levels when methotrexate is used at high doses. Your doctor will monitor this.

Drugs That Lower Gleevec Levels

Some drugs can make Gleevec work less well. Your doctor may need to change your medicines.

Drugs That Raise Gleevec Levels

Some drugs can make Gleevec levels too high. Do not drink grapefruit juice while taking Gleevec.

Drugs Processed by CYP3A4

Gleevec can raise levels of other drugs your body processes through CYP3A4. These include:

– Certain anxiety medicines

– Certain blood pressure medicines

– Certain cholesterol medicines

Use caution with these drugs if they need exact dosing. Tell your doctor about all medicines you take.

Blood Thinners (Warfarin)

Warfarin is processed by CYP3A4. Use heparin instead of warfarin for blood thinning if needed.

Drugs Processed by CYP2D6

Use caution with CYP2D6 drugs that need exact dosing. Tell your doctor about all medicines you take.

Methotrexate

Gleevec may raise methotrexate levels when methotrexate is used at high doses. Your doctor will monitor this.

Risk Summary

Gleevec can harm an unborn baby. There have been reports of miscarriages and birth defects in women who took Gleevec during pregnancy. Studies in pregnant rats showed that Gleevec caused birth defects. Women should not get pregnant while taking this drug. If you become pregnant while taking Gleevec, tell your doctor right away. The general risk for birth defects in the U.S. is 2% to 4%. The general risk for miscarriage is 15% to 20%.

Animal Data

Pregnant rats and rabbits were given Gleevec during their pregnancies. In rats, high doses caused birth defects in the babies, including problems with skull development. The babies were also smaller than normal. In rabbits, no problems were seen at similar doses. In another study in rats, some mothers given high doses had babies that were stillborn or died after birth. The babies that survived were smaller than normal. Some female babies also had delayed development.

Risk Summary

Animal Data

Risk Summary

Imatinib (Gleevec) passes into breast milk. Because of the risk of serious side effects in breastfed babies, women should not breastfeed while taking this medicine and for 1 month after the last dose.

Human Data

Studies in 3 breastfeeding women show that the medicine passes into milk at about half the level in the mother’s blood. A breastfed baby could get up to 10% of the mother’s dose based on body weight.

Risk Summary

Human Data

Use in Children

Gleevec has been shown to work in children with newly found Ph+ chronic phase CML and Ph+ ALL. There is no information about use in children under 1 year old.

Use in Children

Gleevec has been shown to work in children with newly found Ph+ chronic phase CML and Ph+ ALL. There is no information about use in children under 1 year old.

CML Studies

About 20 out of 100 patients in CML studies were older than 65 years. In a study of newly diagnosed CML patients, 6 out of 100 were older than 65 years. More older patients had swelling (edema) compared to younger patients. No other differences in safety were found. Gleevec worked the same in older and younger patients.

Unresectable or Metastatic GIST Study

In this study, 16 out of 100 patients were older than 65 years. No clear differences in safety or effectiveness were seen in older patients compared to younger patients. But there were not enough older patients to know for sure.

Adjuvant GIST Study

In this study, 221 patients (31 out of 100) were older than 65 years. No difference in safety was found between older and younger patients, except more swelling in older patients. Gleevec worked the same in older and younger patients.

CML Studies

Unresectable or Metastatic GIST Study

Adjuvant GIST Study

Effect of Liver Problems on Medicine

A study looked at 84 patients with cancer and liver problems. They took imatinib doses from 100 mg to 800 mg.

Mild and moderate liver problems do not change how much imatinib or its breakdown product is in the body.

With severe liver problems:
– Imatinib levels increase by 63%
– Imatinib exposure increases by 45%
– CGP74588 (breakdown product) levels increase by 56%
– CGP74588 exposure increases by 55%

Dose Change

Reduce the dose by 25% for patients with severe liver problems.

Liver Function Tests

The table below shows how liver function is classified:

ULN = upper limit of normal for the lab
SGOT is now called AST

Effect of Liver Problems on Medicine

A study looked at 84 patients with cancer and liver problems. They took imatinib doses from 100 mg to 800 mg.

Mild and moderate liver problems do not change how much imatinib or its breakdown product is in the body.

With severe liver problems:

– Imatinib levels increase by 63%

– Imatinib exposure increases by 45%

– CGP74588 (breakdown product) levels increase by 56%

– CGP74588 exposure increases by 55%

Dose Change

Reduce the dose by 25% for patients with severe liver problems.

Liver Function Tests

The table below shows how liver function is classified:

| Liver Function | Total Bilirubin | SGOT (AST) |

|—————-|—————–|————|

| Normal | Less than or equal to ULN | Less than or equal to ULN |

| Mild | Greater than 1.0–1.5 times ULN | Greater than ULN |

| Moderate | Greater than 1.5–3 times ULN | Any result |

| Severe | Greater than 3–10 times ULN | Any result |

ULN = upper limit of normal for the lab

SGOT is now called AST

Effect of Kidney Problems on Imatinib

A study looked at 59 patients with cancer and different levels of kidney problems. Patients took imatinib doses from 100 to 800 mg each day.

Patients with mild and moderate kidney problems had 1.5 to 2 times more medicine in their body than patients with normal kidneys.

There is not enough information about patients with severe kidney problems.

Patients with moderate and severe kidney problems need lower doses of this medicine.

Kidney Function Levels

– Mild: Kidneys working at 40-59 mL/min
– Moderate: Kidneys working at 20-39 mL/min
– Severe: Kidneys working at less than 20 mL/min

Effect of Kidney Problems on Imatinib

A study looked at 59 patients with cancer and different levels of kidney problems. Patients took imatinib doses from 100 to 800 mg each day.

Patients with mild and moderate kidney problems had 1.5 to 2 times more medicine in their body than patients with normal kidneys.

There is not enough information about patients with severe kidney problems.

Patients with moderate and severe kidney problems need lower doses of this medicine.

Kidney Function Levels

– Mild: Kidneys working at 40-59 mL/min

– Moderate: Kidneys working at 20-39 mL/min

– Severe: Kidneys working at less than 20 mL/min

What It Is

Imatinib is a medicine taken by mouth. The brand name is Gleevec. It comes as film-coated tablets.

Strengths

Gleevec comes in two strengths:
– 100 mg tablets
– 400 mg tablets

What Each Tablet Contains

Each 100 mg tablet contains 119.5 mg of imatinib mesylate, which equals 100 mg of imatinib.
Each 400 mg tablet contains 478 mg of imatinib mesylate, which equals 400 mg of imatinib.

Imatinib mesylate is a white to off-white powder. It dissolves easily in acidic liquids but does not dissolve well in neutral or alkaline liquids.

Other Ingredients

Inactive ingredients (added to make the tablet):
– Colloidal silicon dioxide
– Crospovidone
– Hydroxypropyl methylcellulose
– Magnesium stearate
– Microcrystalline cellulose

Tablet coating:
– Red ferric oxide
– Yellow ferric oxide
– Hydroxypropyl methylcellulose
– Polyethylene glycol
– Talc

What It Is

Imatinib is a medicine taken by mouth. The brand name is Gleevec. It comes as film-coated tablets.

Strengths

Gleevec comes in two strengths:

– 100 mg tablets

– 400 mg tablets

What Each Tablet Contains

Each 100 mg tablet contains 119.5 mg of imatinib mesylate, which equals 100 mg of imatinib.

Each 400 mg tablet contains 478 mg of imatinib mesylate, which equals 400 mg of imatinib.

Imatinib mesylate is a white to off-white powder. It dissolves easily in acidic liquids but does not dissolve well in neutral or alkaline liquids.

Other Ingredients

Inactive ingredients (added to make the tablet):

– Colloidal silicon dioxide

– Crospovidone

– Hydroxypropyl methylcellulose

– Magnesium stearate

– Microcrystalline cellulose

Tablet coating:

– Red ferric oxide

– Yellow ferric oxide

– Hydroxypropyl methylcellulose

– Polyethylene glycol

– Talc

How This Medicine Works

Imatinib mesylate is a medicine that blocks certain proteins in your body. It blocks a protein called BCR-ABL that causes a type of leukemia called chronic myeloid leukemia (CML). This medicine stops the leukemia cells from growing and can kill them.

In lab studies, this medicine slowed down tumor growth in mice that had leukemia cells from CML patients.

This medicine also blocks other proteins called PDGF and SCF. These proteins are involved in a cancer called GIST (gastrointestinal stromal tumor). In lab studies, Imatinib stopped GIST cells from growing and killed them.

How This Medicine Works

In lab studies, this medicine slowed down tumor growth in mice that had leukemia cells from CML patients.

How the Body Processes Gleevec

Studies looked at how Gleevec works in the body. Over 900 patients were studied. The drug behaves the same in CML and GIST patients.

Absorption and Distribution

Gleevec is absorbed well after taking by mouth. Highest levels in the blood are reached 2 to 4 hours after a dose. About 98% of the drug enters the bloodstream. Drug levels increase with higher doses (25 mg to 1,000 mg). No major change in how the drug works with repeated dosing. Drug builds up 1.5 to 2.5 times when taken once daily. About 95% of the drug binds to proteins in the blood (mainly albumin).

Metabolism

CYP3A4 is the main enzyme that breaks down Gleevec. Other enzymes play a smaller role. The main active breakdown product is N-demethylated metabolite. This metabolite works similar to the parent drug. This metabolite level is about 15% of the parent drug level. Protein binding is similar to the parent drug.

Elimination

Gleevec leaves the body mostly in feces, mostly as breakdown products. About 81% of the dose is eliminated within 7 days. Of this, 68% is in feces and 13% is in urine. Unchanged drug accounts for 25% of the dose (5% urine, 20% feces). The rest is breakdown products.

The half-life of Gleevec is about 18 hours. The half-life of the major active metabolite is about 40 hours.

In a 50-year-old patient weighing 50 kg, drug clearance is about 8 liters per hour. In a 50-year-old patient weighing 100 kg, clearance is about 14 liters per hour. Differences in how patients process the drug (40% variability) do not require starting dose changes based on weight or age. But patients should be monitored closely for side effects.

Liver Problems

Liver problems do not greatly affect Gleevec levels in patients with mild or moderate liver impairment. Patients with severe liver impairment have higher drug levels. In severe liver impairment, peak drug levels increase by about 63% and total drug exposure increases by about 45%. Dose reduction is needed for patients with severe liver impairment.

Kidney Problems

Kidney problems affect Gleevec levels. In mild to moderate kidney impairment, drug exposure increases 1.5 to 2 times compared to normal kidney function. In mild kidney impairment, doses above 600 mg do not increase exposure further. In moderate kidney impairment, doses above 400 mg do not increase exposure further. Patients with severe kidney impairment have similar exposure at 100 mg daily as normal patients at 400 mg daily. Dose reduction is needed for moderate and severe kidney impairment.

Children

In children, Gleevec is absorbed quickly. Highest levels are reached in 2 to 4 hours. Drug clearance is similar to adults (11.0 L/hr/m² in children vs 10.0 L/hr/m² in adults). Half-life is similar (14.8 hours in children vs 17.1 hours in adults). Children receiving 260 mg/m² or 340 mg/m² have drug exposure similar to adults receiving 400 mg. Drug builds up 1.5 to 2.2 times with repeated daily dosing.

Drug Interactions

Some drugs can affect Gleevec levels:

– Rifampin and other enzyme-inducing drugs (such as carbamazepine, phenytoin, phenobarbital) can lower Gleevec levels significantly. Gleevec dose may need to be increased.
– St. John’s Wort reduces Gleevec exposure by 30%.
– Strong CYP3A4 inhibitors (such as ketoconazole, itraconazole, clarithromycin, ritonavir) can increase Gleevec levels. Caution is needed. Grapefruit juice should be avoided.

Gleevec can increase levels of other drugs:

– Gleevec increases levels of simvastatin (a cholesterol drug) 2 to 3.5 times.
– Caution is needed with drugs that have a narrow therapeutic window (such as alfentanil, cyclosporine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus).
– Warfarin (a blood thinner) should be avoided. Use heparin instead.

Gleevec has a weak effect on CYP2D6 drugs (such as metoprolol). No dose adjustment is needed but caution is recommended.

Acetaminophen (Tylenol) does not affect Gleevec levels at 400 mg daily. There is no data on higher doses or chronic use together.

Lab Effects

Gleevec affects certain liver enzymes. It inhibits CYP2C9 and CYP2D6. It also affects some transport proteins in the body.

How the Body Processes Gleevec

Studies looked at how Gleevec works in the body. Over 900 patients were studied. The drug behaves the same in CML and GIST patients.

Absorption and Distribution

Metabolism

Elimination

The half-life of Gleevec is about 18 hours. The half-life of the major active metabolite is about 40 hours.

Liver Problems

Kidney Problems

Children

Drug Interactions

Some drugs can affect Gleevec levels:

– Rifampin and other enzyme-inducing drugs (such as carbamazepine, phenytoin, phenobarbital) can lower Gleevec levels significantly. Gleevec dose may need to be increased.

– St. John’s Wort reduces Gleevec exposure by 30%.

– Strong CYP3A4 inhibitors (such as ketoconazole, itraconazole, clarithromycin, ritonavir) can increase Gleevec levels. Caution is needed. Grapefruit juice should be avoided.

Gleevec can increase levels of other drugs:

– Gleevec increases levels of simvastatin (a cholesterol drug) 2 to 3.5 times.

– Caution is needed with drugs that have a narrow therapeutic window (such as alfentanil, cyclosporine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus).

– Warfarin (a blood thinner) should be avoided. Use heparin instead.

Gleevec has a weak effect on CYP2D6 drugs (such as metoprolol). No dose adjustment is needed but caution is recommended.

Acetaminophen (Tylenol) does not affect Gleevec levels at 400 mg daily. There is no data on higher doses or chronic use together.

Lab Effects

Gleevec affects certain liver enzymes. It inhibits CYP2C9 and CYP2D6. It also affects some transport proteins in the body.

[med_microbiology]

[med_pharmacogenomics]

[med_immunogenicity]

[med_references]

Chronic Myeloid Leukemia (CML) – Newly Diagnosed, Early Stage

A large study compared two treatments for patients with a type of leukemia called chronic myeloid leukemia (CML) in its early stage. The study included 1,106 patients from 16 countries. One group received Gleevec alone. The other group received interferon-alpha plus cytarabine (chemotherapy). Patients could switch to the other treatment if their cancer got worse or they couldn’t handle the side effects.

The study found:
– More patients responded to Gleevec (97% had blood counts improve) compared to the other treatment (57%)
– More patients had their cancer cells decrease with Gleevec (85%) versus the other treatment (17%)
– After 7 years, 81% of Gleevec patients were alive without their cancer getting worse, compared to 61% on the other treatment
– Fewer patients on Gleevec had their cancer progress to advanced stages (7%) compared to the other treatment (30%)
– The average daily dose of Gleevec was about 406 mg

A second study compared Gleevec to another medicine called nilotinib. This study included 846 patients. Results showed:
– Nilotinib worked faster – 44% of nilotinib patients had a major molecular response at 12 months, compared to 22% on Gleevec
– By 5 years, 77% of nilotinib patients had a major molecular response, compared to 60% on Gleevec
– More patients on nilotinib had their cancer cells disappear completely (80%) at 12 months compared to Gleevec (65%)
– Survival was similar in both groups (about 92% to 94% alive at 5 years)

Late Stage CML and Advanced CML

Three separate studies tested Gleevec in patients with more advanced CML or CML that didn’t respond to interferon treatment:

1. CML that didn’t respond to interferon: 532 patients were treated. Most patients (95%) had their blood counts improve. About 60% had their cancer cells decrease significantly. After 2 years, 86% of patients who responded were still doing well.

2. Accelerated phase CML (cancer getting worse): 235 patients were treated. About 71% had their blood counts improve. The higher dose (600 mg) worked better than the lower dose (400 mg) – 75% versus 64% responded. Median survival was about 20.9 months on the lower dose and had not been reached yet on the higher dose.

3. Blast crisis CML (most advanced stage): 260 patients were treated. About 31% had their blood counts improve. The higher dose (600 mg) worked better than the lower dose (400 mg) – 33% versus 16% responded. Median survival was about 6.9 months.

Pediatric CML

Fifty-one children with newly diagnosed CML were treated with Gleevec. Results showed:
– 78% had their blood counts return to normal
– 65% had their cancer cells disappear completely
– Most children who responded did so between 3 and 10 months

Another study included 14 children with CML that came back after stem cell transplant or didn’t respond to interferon. Four patients had a major cytogenetic response, and 7 had their cancer cells disappear completely.

Acute Lymphoblastic Leukemia (ALL)

Forty-three adults with a specific type of ALL (Ph+ ALL) that had returned or didn’t respond to other treatment received Gleevec. Results showed:
– 19% had their blood counts return to normal
– 35% had a major cytogenetic response
– 21% had their cancer cells disappear completely
– Median duration of response was about 3.4 months

Pediatric ALL

A study tested Gleevec combined with chemotherapy in 92 children and young adults with high-risk Ph+ ALL. Patients received Gleevec along with chemotherapy, and some also received stem cell transplant. The estimated 4-year event-free survival was 70%. In the group that received the most Gleevec (cohort 5), 50 patients were treated – 30 with chemotherapy plus Gleevec, and 20 with chemotherapy plus Gleevec followed by stem cell transplant.

Myelodysplastic/Myeloproliferative Diseases (MDS/MPD)

Thirty-one patients with MDS/MPD were treated with Gleevec 400 mg daily. Results showed:
– 45% had their blood counts return to normal
– 39% had a major cytogenetic response
– Patients with a specific gene change involving chromosome 5 or 4 had the best response (79% to 100% had complete hematologic response)
– Patients without this gene change had much lower response rates (7%)

Aggressive Systemic Mastocytosis (ASM)

Twenty-eight patients with ASM were treated with Gleevec. Results showed:
– 29% had their blood counts return to normal
– 32% had partial improvement
– Patients with a specific gene change called FIP1L1-PDGFRα fusion kinase had the best response (100% had complete response)
– Patients with the D816V mutation generally did not respond to Gleevec

Gleevec is not recommended for less aggressive forms of mastocytosis.

Hypereosinophilic Syndrome / Chronic Eosinophilic Leukemia (HES/CEL)

One hundred seventy-six patients with HES/CEL were treated with Gleevec. Results showed:
– 61% had their blood counts return to normal
– 13% had partial improvement
– Patients with the FIP1L1-PDGFRα gene change had the best response (100% had complete response)
– Patients without this gene change had lower response rates (21% complete response)

Dermatofibrosarcoma Protuberans (DFSP)

Eighteen patients with DFSP were treated with Gleevec. This is a type of skin cancer. Results showed:
– 39% had their tumor disappear completely
– 44% had their tumor shrink
– Overall, 83% responded to treatment
– Patients with the PDGF B gene rearrangement had the best response
– Some patients became disease-free after surgery following partial response

Gastrointestinal Stromal Tumors (GIST)

Two large studies included 1,640 patients with GIST that couldn’t be removed by surgery or had spread. Patients received either 400 mg or 800 mg of Gleevec daily. Results showed:
– Average time before cancer got worse was 19 months on 400 mg and 23 months on 800 mg
– Average survival was about 49 months in both groups
– About 5% had their tumor disappear completely
– About 47% had their tumor shrink
– No significant difference in survival between the two doses

GIST After Surgery (Adjuvant Treatment)

Study 1: 713 patients who had surgery for GIST received either Gleevec or placebo for 12 months. Results showed:
– After 1 year, 21% of Gleevec patients had their cancer return versus 28% of placebo patients
– Gleevec significantly reduced the risk of recurrence

Study 2: 397 patients who had surgery for GIST received either 12 months or 36 months of Gleevec. Results showed:
– After 3 years, 25% of the 36-month group had their cancer return versus 42% of the 12-month group
– The 36-month treatment significantly improved overall survival
– Deaths: 6% in the 36-month group versus 13% in the 12-month group

Figure 1 Progression Free Survival (ITT Principle)

Figure 2 Time to Progression to AP or BC (ITT Principle)

Figure 3: Study 1 Recurrence-Free Survival (ITT Population)

Figure 4: Study 2 Recurrence-Free Survival (ITT Population)

Figure 5: Study 2 Overall Survival (ITT Population)

Table 18: Response in Newly Diagnosed CML Study (84-Month Data)
*p less than 0.001, Fischer’s exact test. 1Hematologic response criteria (all responses to be confirmed after greater than or equal to 4 weeks): WBC less than 10 x 109/L, platelet less than 450 x 109/L, myelocyte + metamyelocyte less than 5% in blood, no blasts and promyelocytes in blood, no extramedullary involvement. 2Cytogenetic response criteria (confirmed after greater than or equal to 4 weeks): complete (0% Ph+ metaphases) or partial (1%-35%). A major response (0%-35%) combines both complete and partial responses. 3Unconfirmed cytogenetic response is based on a single bone marrow cytogenetic evaluation, therefore unconfirmed complete or partial cytogenetic responses might have had a lesser cytogenetic response on a subsequent bone marrow evaluation.
Best response rate	Gleevec n = 553	IFN+Ara−C n = 553
Hematologic response1
CHR rate n (%)	534 (96.6%)*	313 (56.6%)*
[95% CI]	[94.7%, 97.9%]	[52.4%, 60.8%]
Cytogenetic response2
Major cytogenetic response n (%)	472 (85.4%)*	93 (16.8%)*
[95% CI]	[82.1%, 88.2%]	[13.8%, 20.2%]
Unconfirmed3	88.6%*	23.3%*
Complete cytogenetic response n (%)	413 (74.7%)*	36 (6.5%)*
[95% CI]	[70.8, 78.3]	[4.6, 8.9]
Unconfirmed3	82.5%*	11.6%*

Table 19: Efficacy (MMR and CCyR) of Gleevec Compared to Nilotinib in Newly Diagnosed Ph+ CML-CP
Abbreviations: CCyR, complete cytogenetic response; MMR, major molecular response; Ph+ CML-CP, Philadelphia chromosome positive chronic myeloid leukemia-chronic phase. aCMH test stratified by Sokal risk group. bCCyR: 0% Ph+ metaphases. Cytogenetic responses were based on the percentage of Ph-positive metaphases among greater than or equal to 20 metaphase cells in each bone marrow sample.
	Gleevec 400 mg once daily	Nilotinib 300 mg twice daily
	N = 283	N = 282
MMR at 12 months (95% CI)	22% (17.6, 27.6)	44% (38.4, 50.3)
P-Valuea	< 0.0001
CCyRb by 12 months (95% CI)	65% (59.2, 70.6)	80% (75.0, 84.6)
MMR at 24 months (95% CI)	38% (31.8, 43.4)	62% (55.8, 67.4)
CCyRb by 24 months (95% CI)	77% (71.7, 81.8)	87% (82.4, 90.6)

Table 20: Response in Chronic Myeloid Leukemia Studies
Abbreviations: BM, bone marrow; PB, peripheral blood. 1Hematologic response criteria (all responses to be confirmed after greater than or equal to 4 weeks): CHR: Chronic phase study [WBC less than 10 x 109/L, platelet less than 450 x 109/L, myelocytes + metamyelocytes less than 5% in blood, no blasts and promyelocytes in blood, basophils less than 20%, no extramedullary involvement] and in the accelerated and blast crisis studies [absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L, platelets greater than or equal to 100 x 109/L, no blood blasts, BM blasts less than 5% and no extramedullary disease]. NEL: Same criteria as for CHR but ANC greater than or equal to 1 x 109/L and platelets greater than or equal to 20 x 109/L (accelerated and blast crisis studies). RTC: less than 15% blasts BM and PB, less than 30% blasts + promyelocytes in BM and PB, less than 20% basophils in PB, no extramedullary disease other than spleen and liver (accelerated and blast crisis studies). 2Cytogenetic response criteria (confirmed after greater than or equal to 4 weeks): complete (0% Ph+ metaphases) or partial (1%-35%). A major response (0%-35%) combines both complete and partial responses. 3Unconfirmed cytogenetic response is based on a single bone marrow cytogenetic evaluation, therefore unconfirmed complete or partial cytogenetic responses might have had a lesser cytogenetic response on a subsequent bone marrow evaluation. 4Complete cytogenetic response confirmed by a second bone marrow cytogenetic evaluation performed at least 1 month after the initial bone marrow study.
	Chronic phase IFN failure (n = 532)	Accelerated phase (n = 235)	Myeloid blast crisis (n = 260)
		600 mg n = 158	600 mg n = 223
	400 mg	400 mg n = 77	400 mg n = 37
	% of patients [CI 95%]
Hematologic response1	95% [92.3−96.3]	71% [64.8−76.8]	31% [25.2−36.8]
Complete hematologic response (CHR)	95%	38%	7%
No evidence of leukemia (NEL)	Not applicable	13%	5%
Return to chronic phase (RTC)	Not applicable	20%	18%
Major cytogenetic response2	60% [55.3−63.8]	21% [16.2−27.1]	7% [4.5−11.2]
(Unconfirmed3)	(65%)	(27%)	(15%)
Complete4 (Unconfirmed3)	39% (47%)	16% (20%)	2% (7%)

Table 21: Effect of Gleevec on Relapsed/Refractory Ph+ ALL
Abbreviations: CCyR, complete cytogenetic response; CHR, complete hematologic response; MCyR, major cytogenetic response; NEL, no evidence of leukemia; PCyR, partial cytogenic response; Ph+ ALL, Philadelphia chromosome positive acute lymphoblastic leukemia; PHR, partial hematologic response; RTC, return to chronic phase.
	Phase 2 study (N = 43) n (%)	Phase 1 study (N = 2) n (%)
CHR	8 (19)	2 (100)
NEL	5 (12)
RTC/PHR	11 (26)
MCyR	15 (35)
CCyR	9 (21)
PCyR	6 (14)

Table 22: Response in MDS/MPD
Abbreviations: NE, not evaluable; MDS/MPD, myelodysplastic/myeloproliferative disease.
	Number of patients	Complete hematologic response	Major cytogenetic response
	N	N (%)	N (%)
Overall population	31	14 (45)	12 (39)
Chromosome 5 translocation	14	11 (79)	11 (79)
Chromosome 4 translocation	2	2 (100)	1 (50)
Others/no translocation	14	1 (7)	0
Molecular relapse	1	NE	NE

Table 23: Response in ASM
Abbreviations: ASM, aggressive systemic mastocytosis; PDGFR, platelet-derived growth factor receptor. *Patient had concomitant chronic myeloid leukemia CML and ASM.
Cytogenetic abnormality	Number of patients N	Complete hematologic response N (%)	Partial hematologic response N (%)
FIP1L1-PDGFRα fusion kinase (or CHIC2 deletion)	7	7 (100)	0
Juxtamembrane mutation	2	0	2 (100)
Unknown or no cytogenetic abnormality detected	15	0	7 (44)
D816V mutation	4	1* (25)	0
Total	28	8 (29)	9 (32)

Table 24: Response in HES/CEL
Abbreviations: CEL, chronic eosinophilic leukemia; HES, hypereosinophilic syndrome; PDGFR, platelet-derived growth factor receptor.
Cytogenetic abnormality	Number of patients	Complete hematological response N (%)	Partial hematological response N (%)
Positive FIP1L1-PDGFRα fusion kinase	61	61 (100)	0
Negative FIP1L1-PDGFRα fusion kinase	56	12 (21)	9 (16)
Unknown cytogenetic abnormality	59	34 (58)	7 (12)
Total	176	107 (61)	23 (13)

Table 25: Response in DFSP
	Number of patients (n = 18)	%
Complete response	7	39
Partial response*	8	44
Total responders	15	83
*5 patients made disease free by surgery.

Table 26: Overall Survival, Progression-Free Survival and Tumor Response Rates in the Phase 3 GIST Trials
Abbreviation: GIST, gastrointestinal stromal tumors.
	Gleevec 400 mg N = 818	Gleevec 800 mg N = 822
Progression-free survival (months) Median	18.9	23.2
95% CI	17.4–21.2	20.8–24.9
Overall survival (months)	49.0	48.7
95% CI	45.3–60.0	45.3–51.6
Best overall tumor response Complete response Partial response	43 (5.3%) 377 (46.1%)	41 (5.0%) 402 (48.9%)

Chronic Myeloid Leukemia (CML) – Newly Diagnosed, Early Stage

The study found:

– More patients responded to Gleevec (97% had blood counts improve) compared to the other treatment (57%)

– More patients had their cancer cells decrease with Gleevec (85%) versus the other treatment (17%)

– After 7 years, 81% of Gleevec patients were alive without their cancer getting worse, compared to 61% on the other treatment

– Fewer patients on Gleevec had their cancer progress to advanced stages (7%) compared to the other treatment (30%)

– The average daily dose of Gleevec was about 406 mg

A second study compared Gleevec to another medicine called nilotinib. This study included 846 patients. Results showed:

– Nilotinib worked faster – 44% of nilotinib patients had a major molecular response at 12 months, compared to 22% on Gleevec

– By 5 years, 77% of nilotinib patients had a major molecular response, compared to 60% on Gleevec

– More patients on nilotinib had their cancer cells disappear completely (80%) at 12 months compared to Gleevec (65%)

– Survival was similar in both groups (about 92% to 94% alive at 5 years)

Late Stage CML and Advanced CML

Three separate studies tested Gleevec in patients with more advanced CML or CML that didn’t respond to interferon treatment:

Pediatric CML

Fifty-one children with newly diagnosed CML were treated with Gleevec. Results showed:

– 78% had their blood counts return to normal

– 65% had their cancer cells disappear completely

– Most children who responded did so between 3 and 10 months

Acute Lymphoblastic Leukemia (ALL)

Forty-three adults with a specific type of ALL (Ph+ ALL) that had returned or didn’t respond to other treatment received Gleevec. Results showed:

– 19% had their blood counts return to normal

– 35% had a major cytogenetic response

– 21% had their cancer cells disappear completely

– Median duration of response was about 3.4 months

Pediatric ALL

Myelodysplastic/Myeloproliferative Diseases (MDS/MPD)

Thirty-one patients with MDS/MPD were treated with Gleevec 400 mg daily. Results showed:

– 45% had their blood counts return to normal

– 39% had a major cytogenetic response

– Patients with a specific gene change involving chromosome 5 or 4 had the best response (79% to 100% had complete hematologic response)

– Patients without this gene change had much lower response rates (7%)

Aggressive Systemic Mastocytosis (ASM)

Twenty-eight patients with ASM were treated with Gleevec. Results showed:

– 29% had their blood counts return to normal

– 32% had partial improvement

– Patients with a specific gene change called FIP1L1-PDGFRα fusion kinase had the best response (100% had complete response)

– Patients with the D816V mutation generally did not respond to Gleevec

Gleevec is not recommended for less aggressive forms of mastocytosis.

Hypereosinophilic Syndrome / Chronic Eosinophilic Leukemia (HES/CEL)

One hundred seventy-six patients with HES/CEL were treated with Gleevec. Results showed:

– 61% had their blood counts return to normal

– 13% had partial improvement

– Patients with the FIP1L1-PDGFRα gene change had the best response (100% had complete response)

– Patients without this gene change had lower response rates (21% complete response)

Dermatofibrosarcoma Protuberans (DFSP)

Eighteen patients with DFSP were treated with Gleevec. This is a type of skin cancer. Results showed:

– 39% had their tumor disappear completely

– 44% had their tumor shrink

– Overall, 83% responded to treatment

– Patients with the PDGF B gene rearrangement had the best response

– Some patients became disease-free after surgery following partial response

Gastrointestinal Stromal Tumors (GIST)

Two large studies included 1,640 patients with GIST that couldn’t be removed by surgery or had spread. Patients received either 400 mg or 800 mg of Gleevec daily. Results showed:

– Average time before cancer got worse was 19 months on 400 mg and 23 months on 800 mg

– Average survival was about 49 months in both groups

– About 5% had their tumor disappear completely

– About 47% had their tumor shrink

– No significant difference in survival between the two doses

GIST After Surgery (Adjuvant Treatment)

Study 1: 713 patients who had surgery for GIST received either Gleevec or placebo for 12 months. Results showed:

– After 1 year, 21% of Gleevec patients had their cancer return versus 28% of placebo patients

– Gleevec significantly reduced the risk of recurrence

Study 2: 397 patients who had surgery for GIST received either 12 months or 36 months of Gleevec. Results showed:

– After 3 years, 25% of the 36-month group had their cancer return versus 42% of the 12-month group

– The 36-month treatment significantly improved overall survival

– Deaths: 6% in the 36-month group versus 13% in the 12-month group

Table 18: Response in Newly Diagnosed CML Study (84-Month Data)
*p less than 0.001, Fischer’s exact test. 1Hematologic response criteria (all responses to be confirmed after greater than or equal to 4 weeks): WBC less than 10 x 109/L, platelet less than 450 x 109/L, myelocyte + metamyelocyte less than 5% in blood, no blasts and promyelocytes in blood, no extramedullary involvement. 2Cytogenetic response criteria (confirmed after greater than or equal to 4 weeks): complete (0% Ph+ metaphases) or partial (1%-35%). A major response (0%-35%) combines both complete and partial responses. 3Unconfirmed cytogenetic response is based on a single bone marrow cytogenetic evaluation, therefore unconfirmed complete or partial cytogenetic responses might have had a lesser cytogenetic response on a subsequent bone marrow evaluation.
Best response rate	Gleevec n = 553	IFN+Ara−C n = 553
Hematologic response1
CHR rate n (%)	534 (96.6%)*	313 (56.6%)*
[95% CI]	[94.7%, 97.9%]	[52.4%, 60.8%]
Cytogenetic response2
Major cytogenetic response n (%)	472 (85.4%)*	93 (16.8%)*
[95% CI]	[82.1%, 88.2%]	[13.8%, 20.2%]
Unconfirmed3	88.6%*	23.3%*
Complete cytogenetic response n (%)	413 (74.7%)*	36 (6.5%)*
[95% CI]	[70.8, 78.3]	[4.6, 8.9]
Unconfirmed3	82.5%*	11.6%*

Table 19: Efficacy (MMR and CCyR) of Gleevec Compared to Nilotinib in Newly Diagnosed Ph+ CML-CP
Abbreviations: CCyR, complete cytogenetic response; MMR, major molecular response; Ph+ CML-CP, Philadelphia chromosome positive chronic myeloid leukemia-chronic phase. aCMH test stratified by Sokal risk group. bCCyR: 0% Ph+ metaphases. Cytogenetic responses were based on the percentage of Ph-positive metaphases among greater than or equal to 20 metaphase cells in each bone marrow sample.
	Gleevec 400 mg once daily	Nilotinib 300 mg twice daily
	N = 283	N = 282
MMR at 12 months (95% CI)	22% (17.6, 27.6)	44% (38.4, 50.3)
P-Valuea	< 0.0001
CCyRb by 12 months (95% CI)	65% (59.2, 70.6)	80% (75.0, 84.6)
MMR at 24 months (95% CI)	38% (31.8, 43.4)	62% (55.8, 67.4)
CCyRb by 24 months (95% CI)	77% (71.7, 81.8)	87% (82.4, 90.6)

Table 20: Response in Chronic Myeloid Leukemia Studies
Abbreviations: BM, bone marrow; PB, peripheral blood. 1Hematologic response criteria (all responses to be confirmed after greater than or equal to 4 weeks): CHR: Chronic phase study [WBC less than 10 x 109/L, platelet less than 450 x 109/L, myelocytes + metamyelocytes less than 5% in blood, no blasts and promyelocytes in blood, basophils less than 20%, no extramedullary involvement] and in the accelerated and blast crisis studies [absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L, platelets greater than or equal to 100 x 109/L, no blood blasts, BM blasts less than 5% and no extramedullary disease]. NEL: Same criteria as for CHR but ANC greater than or equal to 1 x 109/L and platelets greater than or equal to 20 x 109/L (accelerated and blast crisis studies). RTC: less than 15% blasts BM and PB, less than 30% blasts + promyelocytes in BM and PB, less than 20% basophils in PB, no extramedullary disease other than spleen and liver (accelerated and blast crisis studies). 2Cytogenetic response criteria (confirmed after greater than or equal to 4 weeks): complete (0% Ph+ metaphases) or partial (1%-35%). A major response (0%-35%) combines both complete and partial responses. 3Unconfirmed cytogenetic response is based on a single bone marrow cytogenetic evaluation, therefore unconfirmed complete or partial cytogenetic responses might have had a lesser cytogenetic response on a subsequent bone marrow evaluation. 4Complete cytogenetic response confirmed by a second bone marrow cytogenetic evaluation performed at least 1 month after the initial bone marrow study.
	Chronic phase IFN failure (n = 532)	Accelerated phase (n = 235)	Myeloid blast crisis (n = 260)
		600 mg n = 158	600 mg n = 223
	400 mg	400 mg n = 77	400 mg n = 37
	% of patients [CI 95%]
Hematologic response1	95% [92.3−96.3]	71% [64.8−76.8]	31% [25.2−36.8]
Complete hematologic response (CHR)	95%	38%	7%
No evidence of leukemia (NEL)	Not applicable	13%	5%
Return to chronic phase (RTC)	Not applicable	20%	18%
Major cytogenetic response2	60% [55.3−63.8]	21% [16.2−27.1]	7% [4.5−11.2]
(Unconfirmed3)	(65%)	(27%)	(15%)
Complete4 (Unconfirmed3)	39% (47%)	16% (20%)	2% (7%)

Table 21: Effect of Gleevec on Relapsed/Refractory Ph+ ALL
Abbreviations: CCyR, complete cytogenetic response; CHR, complete hematologic response; MCyR, major cytogenetic response; NEL, no evidence of leukemia; PCyR, partial cytogenic response; Ph+ ALL, Philadelphia chromosome positive acute lymphoblastic leukemia; PHR, partial hematologic response; RTC, return to chronic phase.
	Phase 2 study (N = 43) n (%)	Phase 1 study (N = 2) n (%)
CHR	8 (19)	2 (100)
NEL	5 (12)
RTC/PHR	11 (26)
MCyR	15 (35)
CCyR	9 (21)
PCyR	6 (14)

Table 22: Response in MDS/MPD
Abbreviations: NE, not evaluable; MDS/MPD, myelodysplastic/myeloproliferative disease.
	Number of patients	Complete hematologic response	Major cytogenetic response
	N	N (%)	N (%)
Overall population	31	14 (45)	12 (39)
Chromosome 5 translocation	14	11 (79)	11 (79)
Chromosome 4 translocation	2	2 (100)	1 (50)
Others/no translocation	14	1 (7)	0
Molecular relapse	1	NE	NE

Table 23: Response in ASM
Abbreviations: ASM, aggressive systemic mastocytosis; PDGFR, platelet-derived growth factor receptor. *Patient had concomitant chronic myeloid leukemia CML and ASM.
Cytogenetic abnormality	Number of patients N	Complete hematologic response N (%)	Partial hematologic response N (%)
FIP1L1-PDGFRα fusion kinase (or CHIC2 deletion)	7	7 (100)	0
Juxtamembrane mutation	2	0	2 (100)
Unknown or no cytogenetic abnormality detected	15	0	7 (44)
D816V mutation	4	1* (25)	0
Total	28	8 (29)	9 (32)

Table 24: Response in HES/CEL
Abbreviations: CEL, chronic eosinophilic leukemia; HES, hypereosinophilic syndrome; PDGFR, platelet-derived growth factor receptor.
Cytogenetic abnormality	Number of patients	Complete hematological response N (%)	Partial hematological response N (%)
Positive FIP1L1-PDGFRα fusion kinase	61	61 (100)	0
Negative FIP1L1-PDGFRα fusion kinase	56	12 (21)	9 (16)
Unknown cytogenetic abnormality	59	34 (58)	7 (12)
Total	176	107 (61)	23 (13)

Table 25: Response in DFSP
	Number of patients (n = 18)	%
Complete response	7	39
Partial response*	8	44
Total responders	15	83
*5 patients made disease free by surgery.

Table 26: Overall Survival, Progression-Free Survival and Tumor Response Rates in the Phase 3 GIST Trials
Abbreviation: GIST, gastrointestinal stromal tumors.
	Gleevec 400 mg N = 818	Gleevec 800 mg N = 822
Progression-free survival (months) Median	18.9	23.2
95% CI	17.4–21.2	20.8–24.9
Overall survival (months)	49.0	48.7
95% CI	45.3–60.0	45.3–51.6
Best overall tumor response Complete response Partial response	43 (5.3%) 377 (46.1%)	41 (5.0%) 402 (48.9%)

Dosing and Administration

Take Gleevec exactly as your doctor prescribes. Do not change your dose or stop taking it unless your doctor tells you to.

If you miss a dose, take your next dose at the regular time. Do not take two doses at the same time.

Take Gleevec with a meal and a full glass of water.

Fluid Retention and Edema

Gleevec may cause fluid buildup in your body. Call your doctor right away if you gain weight quickly.

Hepatotoxicity

Gleevec may cause liver problems. Call your doctor right away if you have yellow skin or eyes, loss of appetite, bleeding, or bruising.

Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or think you may be pregnant. Women who can become pregnant should not get pregnant while taking Gleevec. Use birth control during treatment and for 14 days after your last dose.

Do not breastfeed during treatment and for 1 month after your last dose.

Drug Interactions

Gleevec can interact with other medicines. Tell your doctor about all medicines you take, including over-the-counter medicines, herbal products, and iron supplements. Avoid grapefruit juice while taking Gleevec.

Pediatric

Growth problems have been reported in children taking Gleevec. The long-term effects on growth are not known. Your doctor will monitor your child’s growth during treatment.

Driving and Using Machines

Gleevec may cause dizziness, blurred vision, or sleepiness. Be careful when driving or using machines.

Dosing and Administration

Take Gleevec exactly as your doctor prescribes. Do not change your dose or stop taking it unless your doctor tells you to.

If you miss a dose, take your next dose at the regular time. Do not take two doses at the same time.

Take Gleevec with a meal and a full glass of water.

Fluid Retention and Edema

Gleevec may cause fluid buildup in your body. Call your doctor right away if you gain weight quickly.

Hepatotoxicity

Gleevec may cause liver problems. Call your doctor right away if you have yellow skin or eyes, loss of appetite, bleeding, or bruising.

Pregnancy and Breastfeeding

Do not breastfeed during treatment and for 1 month after your last dose.

Drug Interactions

Pediatric

Growth problems have been reported in children taking Gleevec. The long-term effects on growth are not known. Your doctor will monitor your child’s growth during treatment.

Driving and Using Machines

Gleevec may cause dizziness, blurred vision, or sleepiness. Be careful when driving or using machines.

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Treats These Conditions

This medication is not currently linked to any conditions.

References

GLEEVEC [prescribing information]. May 2026. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=211ef2da-2868-4a77-8055-1cb2cd78e24b

Accessed: July 1, 2026

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