Imatinib dose reduction after major molecular response in chronic-phase chronic myeloid leukemia.

Abstract

In people with chronic-phase chronic myeloid leukemia (CML) receiving imatinib and achieving major molecular response (MMR), dose reduction may decrease adverse events but may be associated with a loss of molecular response. Whether digital droplet polymerase chain reaction (ddPCR) can identify persons in whom dose reduction might be unsuccessful is unknown. Data from 716 consecutive subjects who achieved MMR after initial imatinib therapy (400 mg/day) were obtained. A total of 486 subjects remained on full-dose imatinib, whereas 230 subjects had their dose reduced to 300 or 200 mg/day. The outcomes of these cohorts were compared via landmark and propensity score matching analyses. Imatinib dose reduction showed no significant effect on the subsequent achievement of deeper molecular responses (4- and 4.5-log reductions in BCR::ABL1 transcripts; MR⁴ and MR^4.5), maintenance of MMR, or attainment of therapy-free remission when compared with subjects without dose reduction. In subjects achieving MR⁴, however, the probability of maintaining MR⁴ (p = .002) was lower in the reduced-dose group. In multivariable analyses, failure to achieve MR^4.5 as determined by ddPCR at the time of dose reduction was significantly associated with briefer MMR failure-free survival (FFS; hazard ratio [HR], 10.3; 95% confidence interval [CI], 1.3-82.9; p = .03) and MR⁴ FFS (HR, 6.8; 95% CI, 2.6-18.0; p < .001). Imatinib dose reduction after achieving MMR does not adversely affect response deepening or MMR maintenance in chronic-phase CML but compromises MR⁴ maintenance. The results of ddPCR may identify people who benefit from imatinib dose reduction.