Predicting Outcomes in Patients With Chronic Myeloid Leukemia at Any Time During Tyrosine Kinase Inhibitor Therapy

Abstract

Current recommendations for monitoring patients with chronic myeloid leukemia (CML) provide recommendations for response assessment and treatment only at 3, 6, 12, and 18 months. These recommendations are based on clinical trial outcomes computed from treatment start. Conditional survival estimates take into account the changing hazard rates as time from treatment elapses as a continuum. We performed conditional survival analyses among patients with CML to improve prognostication at any time point during the course of therapy. We used 2 cohorts of patients with CML in chronic phase: 1 treated in the frontline DASISION (Dasatinib versus Imatinib Study in Treatment - Naïve CML) phase III study (n = 519) and another treated after imatinib treatment had failed in the dasatinib dose-optimization phase III CA180-034 study (n = 670). Conditional survival estimates were calculated. A modified Cox proportional hazards model was used to build a prognostic nomogram. As the time alive or free from events from commencement of treatment increased, conditional survival estimates changed. No differences were observed regarding future outcomes between patients treated with imatinib or dasatinib in the frontline setting for patients with the same breakpoint cluster region-abelson 1 (BCR-ABL1) transcript levels evaluated at the same time point. Age older than 60 years greatly affected future outcomes particularly in the short-term. Conditional survival-based nomograms allowed the prediction of future outcomes at any time point. In summary, we designed a calculator to predict future outcomes of patients with CML at any time point during the course of therapy.