Imatinib — Drug Monograph

Brand names: Gleevec, Glivec

Drug class: Tyrosine Kinase Inhibitor

Mechanism of Action

First targeted kinase inhibitor for cancer. Binds the BCR-ABL ATP-binding site in its inactive (closed) conformation, inhibiting autophosphorylation and downstream signaling. Also inhibits KIT (c-Kit) and PDGFR-α/β. Originally designed for CML driven by BCR-ABL fusion (Philadelphia chromosome); also active in GIST driven by KIT mutations.

FDA Indications

• Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) — chronic, accelerated, and blast phases; all ages
• Ph+ acute lymphoblastic leukemia (ALL) — after failure of prior therapy
• Myelodysplastic/myeloproliferative diseases associated with PDGFR gene rearrangements
• Aggressive systemic mastocytosis (ASM) — without D816V c-Kit mutation
• Hypereosinophilic syndrome / chronic eosinophilic leukemia
• Dermatofibrosarcoma protuberans — unresectable, recurrent, or metastatic
• Gastrointestinal stromal tumor (GIST) — KIT (CD117) positive; unresectable/metastatic; adjuvant after surgical resection

Common Side Effects

• Nausea, vomiting, diarrhea (take with food)
• Edema (periorbital, lower extremity)
• Muscle cramps
• Fatigue
• Rash, dermatitis
• Myelosuppression
• Hepatotoxicity

Clinical Pearl

BCR-ABL PCR is used to monitor treatment response — the target is a major molecular response (MMR): BCR-ABL ≤0.1% on the International Scale (IS). If BCR-ABL is rising or treatment failure occurs, mutation testing for ABL kinase domain mutations guides selection of second-generation TKI. The T315I "gatekeeper" mutation confers resistance to all TKIs except ponatinib and asciminib.

Related Therapies & Mechanisms

• Asciminib (Scemblix) — Tyrosine Kinase Inhibitor · Leukemia
• Dasatinib (Sprycel) — Tyrosine Kinase Inhibitor · Leukemia
• Ibrutinib (Imbruvica) — Tyrosine Kinase Inhibitor · Leukemia
• Idelalisib (Zydelig) — Tyrosine Kinase Inhibitor · Leukemia