What is Gleevec (Imatinib) Used For?
Gleevec (imatinib mesylate) is a selective tyrosine kinase inhibitor primarily used to treat Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) and gastrointestinal stromal tumors (GIST), along with several other malignancies driven by specific kinase abnormalities. 1
Primary FDA-Approved Indications
Hematologic Malignancies
Chronic Myeloid Leukemia (CML):
- Newly diagnosed Ph+ CML in chronic phase (adults and pediatrics) - this is the most common and well-established use 1
- Ph+ CML in blast crisis, accelerated phase, or chronic phase after interferon-alpha failure 1
- Standard dosing is 400 mg daily for chronic phase and 600 mg daily for accelerated phase or blast crisis 2
Acute Lymphoblastic Leukemia (ALL):
- Adult patients with relapsed or refractory Ph+ ALL 1
- Pediatric patients with newly diagnosed Ph+ ALL in combination with chemotherapy 1
- Dosing is 600 mg daily for adults and 340 mg/m² daily for pediatrics 1
Other Hematologic Conditions:
- Myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with PDGFR gene rearrangements at 400 mg daily 1
- Hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) with FIP1L1-PDGFRα fusion kinase at 100-400 mg daily 1
- Aggressive systemic mastocytosis (ASM) without D816V c-Kit mutation at 100-400 mg daily 1
Solid Tumors
Gastrointestinal Stromal Tumors (GIST):
- Kit (CD117) positive unresectable and/or metastatic GIST at 400 mg daily 2, 1
- Adjuvant treatment following complete resection of Kit-positive GIST - recommended for 3 years in high-risk patients 2
- Standard dose is 400 mg daily, with clinical benefit rates of 90-91% in metastatic disease 2
Dermatofibrosarcoma Protuberans (DFSP):
- Unresectable, recurrent and/or metastatic DFSP at 800 mg daily (administered as 400 mg twice daily) 1
Mechanism of Action
Imatinib functions as a selective protein tyrosine kinase inhibitor targeting multiple kinases 2:
- BCR-ABL (the Philadelphia chromosome fusion protein in CML)
- KIT (c-Kit receptor, mutated in GIST)
- PDGFR (platelet-derived growth factor receptors alpha and beta)
The drug inhibits proliferation and induces apoptosis in cells expressing these abnormal kinases 1, 3
Response Rates and Efficacy
In CML:
- Complete hematologic response (CHR) achieved in 93-94% of newly diagnosed chronic phase patients 2
- Major cytogenetic response (MCyR) rates of 85-90% at 12-18 months 2
- Overall survival rates remain high after 5 years, with imatinib demonstrating superior outcomes compared to historical interferon-alpha therapy 2, 4
In GIST:
- Response rates vary significantly by genotype: KIT exon 11 mutations show 72% objective response, KIT exon 9 mutations show 38% response, and wild-type GIST shows 28% response 2
- Primary resistance rates are 5% for KIT exon 11,16% for KIT exon 9, and 23% for wild-type GIST 2
- D842V PDGFRα mutation confers resistance and is a contraindication to imatinib therapy regardless of risk classification 2
Important Clinical Considerations
Dosing Administration:
- All doses should be taken with a meal and a large glass of water 1
- Doses of 800 mg should be administered as 400 mg twice daily to reduce iron exposure 1
- Tablets can be dissolved in water or apple juice for patients with swallowing difficulties 1
Common Adverse Effects:
- Mild-to-moderate edema, nausea, diarrhea, muscle cramps, and rash are most frequent 2, 5
- Myelosuppression (neutropenia and thrombocytopenia) occurs in 14-19% of patients 6, 5
- Hepatic transaminase elevations occur less frequently and typically resolve with treatment interruption 5, 7
- Congestive heart failure is rare (1.7%) and occurs at rates similar to the general population 2
Contraindications and Precautions: