Published 2022
| Version v1
Publication
INCB84344-201: Ponatinib and steroids in frontline therapy for unfit patients with Ph+ acute lymphoblastic leukemia
Creators
- Martinelli, Giovanni
- Papayannidis, Cristina
- Piciocchi, Alfonso
- Robustelli, Valentina
- Soverini, Simona
- Terragna, Carolina
- Marconi, Giovanni
- Lemoli, Roberto M
- Guolo, Fabio
- Fornaro, Antonella
- Lunghi, Monia
- de Fabritiis, Paolo
- Candoni, Anna
- Selleri, Carmine
- Simonetti, Federico
- Bocchia, Monica
- Vitale, Antonella
- Frison, Luca
- Tedeschi, Alessandra
- Cuneo, Antonio
- Bonifacio, Massimiliano
- Martelli, Maria Paola
- D'Ardia, Stefano
- Trappolini, Silvia
- Tosi, Patrizia
- Galieni, Piero
- Fabbiano, Francesco
- Abbenante, Maria Chiara
- Granier, Muriel
- Zhu, Zhaoyin
- Wang, Mingyue
- Sartor, Chiara
- Paolini, Stefania
- Cavo, Michele
- Foà, Robin
- Fazi, Paola
- Vignetti, Marco
- Baccarani, Michele
Contributors
Others:
- Martinelli, Giovanni
- Papayannidis, Cristina
- Piciocchi, Alfonso
- Robustelli, Valentina
- Soverini, Simona
- Terragna, Carolina
- Marconi, Giovanni
- Lemoli, Roberto M
- Guolo, Fabio
- Fornaro, Antonella
- Lunghi, Monia
- de Fabritiis, Paolo
- Candoni, Anna
- Selleri, Carmine
- Simonetti, Federico
- Bocchia, Monica
- Vitale, Antonella
- Frison, Luca
- Tedeschi, Alessandra
- Cuneo, Antonio
- Bonifacio, Massimiliano
- Martelli, Maria Paola
- D'Ardia, Stefano
- Trappolini, Silvia
- Tosi, Patrizia
- Galieni, Piero
- Fabbiano, Francesco
- Abbenante, Maria Chiara
- Granier, Muriel
- Zhu, Zhaoyin
- Wang, Mingyue
- Sartor, Chiara
- Paolini, Stefania
- Cavo, Michele
- Foà, Robin
- Fazi, Paola
- Vignetti, Marco
- Baccarani, Michele
Description
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 ≥60 years, or unfit for intensive chemotherapy and stem cell transplantation. Forty-four patients received oral ponatinib 45 mg/d for 48 weeks (core phase), with prednisone tapered to 60 mg/m2/d from days-14-29. 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) in 18/44 patients (40.9%) at 24 weeks. 61.4% of patients completed the core phase. As of 24 April 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 increase (15.9%), erythema (15.9%), and γ-glutamyltransferase increase (15.9%). Cardiac and vascular TEAEs occurred in 29.5% (grade ≥3, 18.2%) and 27.3% (grade ≥3, 15.9%), respectively. Dose reductions, interruptions, and discontinuations due to TEAEs occurred in 43.2%, 43.2%, and 27.3% of patients, respectively; 5 patients had fatal TEAEs. Ponatinib and prednisone showed efficacy in unfit patients with Ph+ ALL; however, a lower ponatinib dose may be more appropriate in this population. This trial was registered at www.clinicaltrials.gov as #NCT01641107.
Additional details
Identifiers
- URL
- http://hdl.handle.net/11567/1078678
- URN
- urn:oai:iris.unige.it:11567/1078678
Origin repository
- Origin repository
- UNIGE