Imatinib mesylate (Gleevec, Novartis Pharmaceuticals East Manruer, NJ) received 
accelerated approval on May 10, 2001 for the treatment of patients with chronic 
myeloid leukemia (CML) in (a) chronic phase after failure of IFN-alpha therapy, 
(b) accelerated phase, and (c) blast crisis. The accelerated approval was 
accompanied by a postmarketing commitment by Novartis Pharmaceuticals to 
continue patient follow-up to determine duration of treatment response and 
survival. The present review, based on a safety and efficacy report submitted on 
December 20, 2002, summarizes data applicable to the conversion of these three 
CML indications to full approval status.
RESULTS: Chronic phase CML: Five hundred thirty-two chronic phase CML patients 
who had not benefited from prior IFN therapy were treated at a starting imatinib 
mesylate dose of 400 mg p.o. qd; dose escalation to 800 mg p.o. qd was allowed. 
Patients had received a median of 14 months of IFN therapy at doses > or =25 
million IU/wk and were all in late chronic phase, with a median time from 
diagnosis of 32 months. Median duration of imatinib mesylate treatment was 29 
months, with 81% of patients treated for > or =24 months (maximum 31.5 months). 
Initial favorable treatment responses were sustained. An estimated 87.8% of 
patients who had a major cytogenetic response maintained their response 2 years 
after their initial response. After 2 years of treatment, an estimated 85.4% of 
patients were free of progression to accelerated phase or blast crisis, and the 
estimated overall survival was 90.8% (95% confidence interval, 88.3-93.2). 
Accelerated phase CML: Patients enrolled totaled 293: 235 with CML accelerated 
phase, 48 with relapsed/refractory acute lymphocytic leukemia, 2 with 
relapsed/refractory acute myelocytic leukemia, and 8 with relapsed/refractory 
CML in lymphoid blast crisis. Patients received imatinib mesylate 400 or 600 mg 
p.o. qd. Dose escalation was permitted, to a maximum of 800 mg/d, taken as 400 
mg bid. Efficacy results were improved in patients receiving imatinib mesylate 
600 mg qd versus patients receiving 400 mg qd. The median duration of 
hematologic response was 29 versus 17 months and the estimated 24-month 
maintained hematologic response rate was 61% versus 42%. The median survival of 
patients treated with imatinib mesylate 600 mg qd was not reached versus 20.9 
months for patients receiving 400 mg qd. Estimated 24-month survival rate was 
66% versus 46%. The median survival in the advanced leukemia population (acute 
lymphocytic leukemia, acute myelocytic leukemia, and lymphoid blast crisis) was 
only 5 months, and only two patients are still on treatment. Blast crisis CML: A 
total of 260 patients were recruited. The imatinib mesylate dose was initially 
400 mg qd (37 patients) but was subsequently increased to 600 mg qd (223 
patients). Patients receiving imatinib mesylate 600 mg qd had a higher 
hematologic response rate than did patients receiving 400 mg (33% versus 16%). 
Major cytogenetic responses occurred in 15% of the 260 study patients. The 
overall median survival was 6.9 months: 7.1 months for patients treated with 
imatinib mesylate 600 mg and 4.7 months for patients receiving imatinib mesylate 
400 mg. Estimated 12-month survival rate for all study patients was 32.1% and 
estimated 24-month survival rate was 18.3%.
SAFETY: Imatinib mesylate was generally well tolerated, but relatively frequent 
reports of common toxicity criteria grade 3/4 neutropenia and thrombocytopenia 
were encountered. The most frequently reported adverse events included 
gastrointestinal disturbances, edema, rash, and musculoskeletal complaints. 
These rarely led to discontinuation of therapy.
CONCLUSIONS: The results confirm those of the interim analysis and suggest that 
imatinib mesylate represents an effective therapeutic agent for the treatment of 
patients with CML in chronic phase after failure of IFN-alpha therapy, in blast 
crisis, and in accelerated phase.