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

• Published in: Cancer Vol. 131; no. 1; pp. e35565 - n/a
• Main Authors: Li, Zongru, Zhang, Xiaoshuai, Zhao, Yijing, Lu, Linping, Guo, Yong, Gale, Robert Peter, Qin, Yazhen, Jiang, Qian
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2025; John Wiley and Sons Inc
• Subjects: Adult; Aged; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Chronic myeloid leukemia; deep molecular response; digital droplet polymerase chain reaction; dose reduction; Dose-Response Relationship, Drug; Female; Fusion Proteins, bcr-abl - genetics; Humans; Imatinib; Imatinib Mesylate - administration & dosage; Imatinib Mesylate - therapeutic use; Inhibitor drugs; Leukemia; Leukemia, Myeloid, Chronic-Phase - drug therapy; Leukemia, Myeloid, Chronic-Phase - genetics; Maintenance; Male; Middle Aged; Molecular chains; Myeloid leukemia; Original; ORIGINAL ARTICLE; Polymerase chain reaction; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Remission; Statistical analysis; Targeted cancer therapy; Treatment Outcome; dose reduction; chronic myeloid leukemia; imatinib; deep molecular response; digital droplet polymerase chain reaction
• ISSN: 0008-543X; 1097-0142; 1097-0142
• DOI: 10.1002/cncr.35565

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 MR4.5), 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 MR4.5 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. Imatinib dose reduction after achieving major molecular response (MMR) in persons with chronic‐phase chronic myeloid leukemia has no impact on subsequent achievement of MR4 or MR4.5 or MMR maintenance. BCR::ABL1 level detected by digital droplet polymerase chain reaction at the time of dose reduction identifies subjects who are at high risk of losing response to therapy.