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

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.