A Multicenter Prospective Study on Efficacy and Safety of Ponatinib in Patients with Chronic Myeloid Leukemia Resistant or Intolerant to Previous Therapy: A 3-Year Report

▪ Introduction Tyrosine kinase inhibitors (TKIs) have transformed outcomes in chronic myeloid leukemia (CML). Patients who respond to imatinib, have a life expectancy comparable with that of the global population, however, up to 40% of patients discontinue imatinib due to resistance or intolerance. Ponatinib is a third-generation highly-potent-pan-inhibitor of tyrosine kinases, active in all single resistance ABL kinase mutations, including the T315l mutation. This report presents the results of a prospective analysis of 3-year ponatinib therapy available in Poland by Angelini's donation program for patients in all phases of CML resistant or intolerant to previous TKI therapy. Methods 43 CML patients (20 women, 24 men, aged 19 to 76 years, mean age 49 ± 15 years) were treated in 20 Polish Hematology Centers with ponatinib initiated between March 2016 and December 2019. 23 pts (53%) were in the chronic phase (CP), 3 pts (7%) in accelerated phase (AP), and 17 pts (40%) in blastic phase (BP) (9 myeloblastic and 8 lymphoblastic). The majority of patients received three lines of TKI therapy. The T315I mutation was detected in 30% of patients (the initial characteristics of the 43 analyzed patients are shown in Table 1). The indication for ponatinib and its dose schedule was made according to the discretion of the attending physician. The initial dose of ponatinib was 45 mg/d in 60% of all patients (without statistically significant differences in the initial dose between patients starting treatment in CP, AP, and BP). Molecular biology tests were performed according to ELN guidelines and BCR-ABL/ABL ratios were expressed as % [IS] in all patients. Treatment responses were calculated at each specific time points recommended by ELN. Statistica 12 software (StatSoft, Tulsa, OK, USA) was used for calculations. Results The follow-up ranged from one week to 35.4 months (median 11.4 months) (one male patient died on infection one week after ponatinib introduction and was excluded from further analysis, he did not achieve CHR and he transformed to blast phase-BP). The responses to ponatinib are shown in Table 2. Among 23 CP patients, 18 achieved CHR (78%), 6 (26%) MCyR, 5 (22%) CCyR, and 1 (4%) MMR at 1 month of treatment. There were only 2 patients in this group (9%) who did not achieve CHR. Eleven CP patients (48%) achieved stable MMR. In all 3 AP patients, the best responses (CHR, CCyR, and MMR) were maintained until the end of observation (Table 2). Among 17 BP pat