Department of Medical Oncology, Institute Rotary Cancer Hospital All India Institute of Medical Sciences, New Delhi-110 029
†Brijesh Arora - Presently at Department of Medical Oncology Tata Memorial Hospital Mumbai-400 012
*Correspondence to: Lalit Kumar E-mail: lalitaiims@yahoo.com
The tyrosine kinase inhibitor, STI-571 (Imatinib mesylate, Gleevec) has been introduced recently for the treatment of chronic myeloid leukemia (CML). We analysed the results of 118 CML patients treated prospectively with Imatinib. We also compared the results of 79 chronic phase CML patients treated with Imatinib to those with 114 similar patients treated with interferon-μ (IFN-μ).
Patients median age was 38 years, ranging from 13 to 65 years. There were 84 males and 34 females. 79 patients were in chronic phase (CP), 23 accelerated phase (AP) and 16 were in blast crisis (BC) at the time of treatment. 62 patients (CP - 48/79 and advanced CML 14/39) were pre-treated with IFN-μ alone, 43 with hydroxyurea alone, 4 with stem cell transplantation (allogeneic-2, autologous-2) and one with busulfan alone. Imatinib daily dose ranged from 400 mg for chronic phase to 600 mg for patients with advanced CML. Median duration of Imatinib therapy was 6 months, ranging from 1 to 27 months.
96% of patients achieved complete hematologic remission (CHR) at a median interval of 3 weeks. Major cytogenetic response (CGR) rate was 30% and occurred at a median interval of 5 months. Advanced CML : CHR and major CGR rates were 35% and 20%, respectively and median time to achieve response was 34 days and 9 months), respectively. Weight gain, fluid retention, skin rash, nausea were common grade I-II non-haematological toxicities. Grade III-IV neutropenia and thrombocytopenia were seen in 16% & 10% of patients, respectively. A total of 19 patients have died; 14 in the advanced CML group due to progressive disease, 5 in the chronic phase group, 4 of progression to blast crisis and one of bone marrow aplasia and its associated complications.
CHR rates (96% vs 31.6%) and median time to achieve CHR (3 week vs 24 weeks) were significantly higher for patients with imatinib. Major cytogenetic remission rates (30% vs 30%) were similar but time to achieve major CGR was higher for imatinib group (5 months ((2–19 months) vs 6 months (3 to 12 months). Five patients (5/79, 6.3%) developed progressive disease in the imatinib group compared to 19 (16.6%) in the IFN-μ treated group (BC-15, AP 4). Imatinib was stopped in one patient due to toxicity compared to two patients in the interferon group. One patient died of toxicity in the imatinib group, none in the IFN-μ group.
Present study confirms the findings in earlier reports that treatment with imatinib is associated with higher and rapid hematological and cytogenetic responses in patients with chronic phase CML. These results are superior compared to those obtained with interferon a.
