No margin for non-adherence: Probabilistic kaplan-meier modeling of imatinib non-adherence and treatment response in CML (ADAGIO study)

Abstract

Background: Although adherence to imatinib is critical for attaining treatment responses in chronic myeloid leukemia, there is evidence of varying adherence among patients. Our aim was to model and determine the margin of tolerance, if any, required to ensure treatment responses among patients prescribed imatinib before treatment response is at risk.

Method: We performed post hoc analyses of the ADAGIO study conducted in Belgium on 169 evaluable patients (Blood 2009). Applying Kaplan-Meier methods using adherence instead of the conventional time variable, we modeled the likelihood of complete cytogenetic (CCyR), complete hematological (CHR), major molecular (MMR) and optimal (OR) response as a function of 90-day pill count adherence.

Results: Analyses showed that ∼100 % adherence of prescribed dose is associated with probabilities of 0.84 for CHR, 0.83 for CCyR, 0.82 for OR, and 0.77 for MMR; compared to, 0.37 (CHR and CCyR), 0.35 (OR), and 0.39 (MMR) at 90 % adherence. Increasing intake of imatinib from 90 % to 100 % of the prescribed dose increased the likelihood of the various treatment responses by 1.95-2.35-fold.

Conclusion: There is virtually no margin for nonadherence, if the objective is to optimize the likelihood of treatment response, and a minimal margin to avoid impaired treatment response.

Keywords: Adherence; Imatinib; Persistence; “Chronic myeloid leukemia”; “Treatment response”.