Imatinib (IMA) Low Dose Reduction Program (LDR) in Chronic Myeloid Leukemia Ph+ (CML Ph+) in a Single Reference Institution in Mexico City. Ongoing Preliminary Results

Imatinib (IMA) total stop therapy has interesting worldwide results in selected patients (pts) with CML Ph+ who have achieved 4 to 5 log reduction of BCR/ABL copies, however there is no information of LDR.

The observation that IMA intolerance induces a dose reduction in our cases and, the fact that during the follow-up of their RT-PCR for BCR/ABL remains in > 4 log reduction after two years, was the rationale for an open prospective LDR program with the main objective to optimizing CML Ph+ treatment due to economical limitations and drug availability in Mexico. Herein we report our ongoing preliminary results:

A total of 73 of 152 (48%) pts was eligible for LDR after achieving Major Molecular Response (MMR) who reduced of > 4 log in at least two RT-PCR determinations in one or two years. The molecular response was assessed by peripheral blood real-time polymerase chain reaction at selected laboratory, able to express the results according to the International Scale (Hughes T, et al. Blood 2006;108:28-37). LDR included reduction of IMA to 25% of the 400mg for the chronic phase and 33% for the accelerated phase or those who reduced from 800 to 600 and even 400mg.

Among 73 pts, 11 (15%, historic group) were intolerant to IMA and their median dose reduction was 50% (Min-Max; 25-100%) with a median follow-up of 28 months (12-48) with only one relapse after 48 months of dose reduction. The LDR included 62 of 152 (40%) pts with a median age of 37 years (18-74), the gender was, female/male (n-30/32), the median time (MT) duration of CML was 8 years (4-18 years), the MT of reduction was 16 months (12-30). In 52 of 62 pts (83%) the proportion of LDR was 25% and the others in the range of 800 to 400mg. Molecular relapse was seen in 4 cases (6.4%) of the 25% reduction group and in 2 cases of the 50% (600-to 800mg) that represented 1.2%.

The LDR program is an interesting alternative for optimizing CML Ph+ IMA treatment with range from one to two and a half years in MMR with a 7.2% global relapse rate which is lower than the total interruption of TKIs in previous literature reports; however, the inclusion of more pts with follow-up as well, is mandatory to validate our program and the economic impact.