Tyrosine kinase inhibitors have improved survival for patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). However, prognosis for old or unfit patients remains poor. In the INCB84344-201 (formerly GIMEMA LAL 1811) prospective, multicenter, phase 2 trial, we tested the efficacy and safety of ponatinib plus prednisone in newly diagnosed patients with Ph+ ALL aged ≥60 years, or unfit for intensive chemotherapy and stem cell transplantation. Forty-four patients received oral ponatinib 45 mg/day for 48 weeks (core phase), with prednisone tapered to 60 mg/m2/day from days -14 to 29. Prophylactic intrathecal chemotherapy was administered monthly. Median age was 66.5 years (range, 26-85). The primary endpoint (complete hematologic response [CHR] at 24 weeks) was reached in 38/44 patients (86.4%); complete molecular response (CMR) was reached in 18/44 patients (40.9%) at 24 weeks. 61.4% of patients completed the core phase. As of April 24, 2020, median event-free survival was 14.31 months (95% CI 9.30, 22.31). Median overall survival and duration of CHR were not reached; median duration of CMR was 11.6 months. Most common treatment-emergent adverse events (TEAEs) were rash (36.4%), asthenia (22.7%), alanine transaminase increased (15.9%), erythema (15.9%), and gamma-glutamyltransferase increased (15.9%). Cardiac and vascular TEAEs occurred in 29.5% (grade ≥3, 18.2%) and 27.3% (grade ≥3, 15.9%) of patients, respectively. Dose reductions/interruptions/discontinuations due to TEAEs occurred in 43.2%/43.2%/27.3% of patients; 5 patients had fatal TEAEs. Ponatinib and prednisone had efficacy in unfit patients with Ph+ ALL; however, a lower ponatinib dose may be more appropriate in this population. (This trial is registered at www.clinicaltrials.gov as NCT01641107).Copyright © 2021 American Society of Hematology.
About The Expert
Giovanni Martinelli
Cristina Papayannidis
Alfonso Piciocchi
Valentina Robustelli
Simona Soverini
Carolina Terragna
Giovanni Marconi
Roberto Massimo Lemoli
Fabio Guolo
Antonella Fornaro
Monia Lunghi
Paolo de Fabritiis
Anna Candoni
Carmine Selleri
Federico Simonetti
Monica Bocchia
Antonella Vitale
Luca Frison
Alessandra Tedeschi
Antonio Cuneo
Massimiliano Bonifacio
Maria Paola Martelli
Stefano D’Ardia
Silvia Trappolini
Patrizia Tosi
Piero Galieni
Francesco Fabbiano
Maria Chiara Abbenante
Muriel Granier
Zhaoyin Zhu
Mingyue Wang
Chiara Sartor
Stefania Paolini
Michele Cavo
Robin Foà
Paola Fazi
Marco Vignetti
Michele Baccarani
References
PubMed