Molecular monitoring of therapeutic milestones and clinical outcomes in patients with chronic myeloid leukemia

Abstract

Background In the current study, the authors determined whether adhering to molecular monitoring guidelines in patients with chronic myeloid leukemia (CML) is associated with major molecular response (MMR) and assessed barriers to adherent monitoring. Methods Newly treated patients with CML from the Quebec province‐wide CML registry from 2005 to 2016 were included. Timely polymerase chain reaction (tPCR) was defined as the molecular assessment of BCR‐ABL1 at the 3‐month, 12‐month, and 18‐month time points from the initiation of tyrosine kinase inhibitor (TKI) therapy. The cohort was analyzed as a nested case‐control study. Cases with a first‐ever MMR (BCR‐ABL1 ≤0.1%, assessed at any time during follow‐up) were matched to up to 5 controls by duration of TKI therapy, volume of patients with CML at the treatment center, year of cohort entry, and age. Odds ratios (ORs) for the performance of tPCR and MMR were adjusted for sex, comorbidities, type of TKI, and other important covariates. Results The cohort included 496 patients. Of 392 MMR events, 67.9% occurred before 18 months. The performance of tPCR was associated with a doubling of the MMR rate (OR, 2.23; 95% confidence interval [95% CI], 1.56‐3.21) and was similar with 1 to 3 tPCRs performed (P = .67). Furthermore, tPCRs at 3 months (OR, 2.77; 95% CI, 1.81‐4.23) and 12 months (OR, 3.00; 95% CI, 1.64‐5.49) were associated with achieving early MMR, whereas tPCRs at 18 months were not (OR, 1.23; 95% CI, 0.80‐1.89). Low‐volume centers were found to have lower adherence to tPCR (OR, 0.60; 95% CI, 0.40‐0.89). Conclusions Timely molecular assessment at 3 months and 12 months appears to benefit patients with CML. Adherence to timely monitoring should be encouraged, especially in low‐volume treatment centers.

Older patients with chronic myeloid leukemia face suboptimal molecular testing and tyrosine kinase inhibitor adherence

“…Prior analyses of younger patients (median age, <60 years) have shown a greater frequency of molecular monitoring to be associated with an increased rate of achieving major molecular remission, a lower risk of progression to more advanced phases of CML, and improved progression-free survival. 9 , 29 Our study reaffirmed the impact of molecular monitoring on outcomes and demonstrated that 5-year survival was negatively affected by the absence of molecular monitoring during the first year of frontline TKI therapy. Similarly, lesser TKI adherence has been associated with substantially lower rate of complete cytogenetic response and molecular response.…”

“… 6 , 27 , 28 Patients treated at low-volume centers were previously shown to have lower rates of recommended molecular monitoring. 29 Similarly, the SIMPLICITY study demonstrated that patients treated by community providers were less likely to have molecular monitoring when compared with patients treated at academic centers. 21 These data serve as a call to action for better provider education to align real-world patient care with that recommended by consensus guidelines and appropriate care for a highly treatable disease.…”