Co-variates associated with outcomes of tyrosine kinase-inhibitor therapy in persons with chronic myeloid leukaemia initially presenting in accelerated phase

Abstract

We interrogated data from 278 consecutive subjects with chronic myeloid leukaemia (CML) presenting in accelerated phase diagnosed by European LeukemiaNet (ELN) criteria receiving initial imatinib (n = 187) or a 2^nd-generation tyrosine kinase-inhibitor (2G-TKI; n = 91). In multi-variable analyses, blood and/or bone marrow blasts ≥15% (Hazard ratio [HR] = 3.7 [1.6, 8.5], p = 0.003) and blood basophils <3% (HR = 4.6 [2.0, 10.7], p < 0.001) were significantly-associated with worse transformation-free survival (TFS). Age ≥60 years (HR = 4.3 [1.7, 11.4], p = 0.003), platelet concentration <230 × 10E + 9/L (HR = 4.7 [2.0, 10.7], p < 0.001) and blood and/or bone marrow blasts ≥9% (HR = 3.9 [1.7, 8.7], p = 0.001) were significantly-associated with worse survival. Based on number of adverse prognostic co-variates of TFS and survival, respectively, subjects were classified into the low- (none), intermediate- (one) and high-risk (≥2) cohorts with significant difference in TFS and survival (all p < 0.001). In propensity-score matching analysis subjects initially receiving a 2G-TKI had higher cumulative incidences of cytogenetic and molecular responses but similar TFS and survival to those receiving imatinib. Our data should help inform physicians treating person with CML initially presenting in accelerated phase.