A 58-year-old man presents with fatigue and splenomegaly. Peripheral blood shows WBC 85,000/µL with left shift, and bone marrow biopsy confirms chronic myeloid leukemia (CML) in chronic phase with BCR-ABL1 positivity. What is the drug of choice for first-line treatment?
A. Busulfan
B. Interferon-alpha
C. Hydroxyurea
D. Imatinib mesylate
Explanation
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Imatinib mesylate is the standard first-line tyrosine kinase inhibitor (TKI) for BCR-ABL1-positive CML in chronic phase, achieving complete cytogenetic response in >80% of patients.
Mechanism of Action
Imatinib is a selective BCR-ABL1 tyrosine kinase inhibitor that blocks the constitutive kinase activity driving myeloid proliferation in CML.
Dosing and Response
Standard dose: 400 mg daily for chronic phase CML
Leads to complete hematologic response in 95% and complete cytogenetic response in 80–90% at 12 months
Monitoring: BCR-ABL1 transcript levels by qPCR at 3, 6, and 12 months
Why Imatinib Over Other Agents
Table
Feature
Imatinib
Hydroxyurea
Busulfan
IFN-α
Mechanism
BCR-ABL1 TKI
Ribonucleotide reductase inhibitor
Alkylating agent
Immune modulation
Cytogenetic response
80–90%
<10%
<5%
20–30%
Survival benefit
Yes (landmark)
Cytoreduction only
Cytoreduction only
Modest
Tolerability
Excellent
Moderate
Poor (cumulative toxicity)
Poor (flu-like)
Current role
First-line
Cytoreduction in TKI-intolerant
Rarely used
Historical
High-YieldNEET PG
Imatinib revolutionized CML management post-2001 and is the gold standard; second-generation TKIs (dasatinib, nilotinib, bosutinib) are reserved for imatinib resistance or intolerance.
Clinical Pearl
Patients with imatinib-resistant CML (defined as failure to achieve milestones: CHR by 3 months, minor CyR by 6 months, complete CyR by 12 months) should be screened for BCR-ABL1 kinase domain mutations and switched to second-generation TKI.
Mnemonic
TKI-CML = Tyrosine Kinase Inhibitor is the gold standard for CML.
