Real-life Experience With Ponatinib in Chronic Myeloid Leukemia: A Multicenter Observational Study

Abstract Background The strict recruitment criteria of patients for clinical trials often lead to reduced generalizability of its findings. Herein, we aimed to study how ponatinib is used outside clinical trials in patients with chronic myeloid leukemia (CML). Patients & Methods this retrospective study included all patients diagnosed with CML who received ponatinib in 7 medical centers in Israel. Results Between 2011 and 2016, we identified 37 patients with CML who received ponatinib, 21 in chronic phase (CP), and 16 in advanced phase. Only 9 patients (26%) harbored the T315I mutation . All patients received at least 1 prior tyrosine kinase inhibitor. The median age in our cohort was 43 years (range: 9 to 82), significantly younger than is expected for patients with relapsed/refractory CML and 20 years younger than the median age of patients who participated in the PACE trial. During a median follow-up of 14 months (range: 1 to 51), the overall response rate was 85%. Sixteen patients (16/34, 47%) experienced at least major molecular response. Another 16 patients (16/37, 43%) discontinued treatment because of disease progression (N=6), vascular complications (N=1), severe cytopenias (N=2) or for other reasons (N=7). Conclusions In real life, ponatinib is a "niche-drug" that is reserved for a unique population of exceptionally young patients with CML with or without the T315I mutation. In this highly selected group, very different from the PACE cohort, ponatinib achieved high overall response rates.