Ponatinib–Blinatumomab or Imatinib–Chemotherapy for Adult Ph-Positive ALL

BACKGROUND: The outcome of Philadelphia-positive acute lymphoblastic leukemia (Ph-positive ALL) has greatly improved with the use of tyrosine kinase inhibitors and immunotherapy. METHODS: In this trial, we randomly assigned adult patients with Ph-positive ALL in a 2:1 ratio to receive ponatinib plus blinatumomab (intervention group) or imatinib plus chemotherapy (control group) as frontline treatment. A crossover to the intervention group was allowed for patients with persistence or reappearance of measurable residual disease in the control group. The primary end point was event-free survival. RESULTS: A total of 236 patients underwent randomization: 158 to the intervention group and 78 to the control group. The median age of the patients was 55 years (range, 24 to 82). At a median follow-up of 23.7 months, the estimated 24-month event-free survival was 86% in the intervention group and 67% in the control group (P<0.001). Survival with no measurable residual disease was 68% and 42%, respectively. At the end of induction, a complete hematologic response was observed in 94% of the patients in the intervention group and in 79% of those in the control group. After blinatumomab consolidation, a molecular response was observed in 71% and 49% of the patients, respectively. After crossover to the intervention group, 20 of 31 patients (64%) had a molecular response. Overall survival was 90% in the intervention group and 85% in the control group. The cumulative incidence of relapse was 5% and 13%, respectively. As of this report, only 19% of the patients in the intervention group had undergone hematopoietic stem-cell transplantation after having had a first complete hematologic response. CONCLUSIONS: In this phase 3 trial, a frontline chemotherapy-free targeted and immunotherapeutic approach was superior to the use of imatinib and chemotherapy. (Funded by Associazione Italiana per la Ricerca sul Cancro and others; GIMEMA ALL2820 ClinicalTrials.gov number, NCT04722848.).

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Publication Details

Journal
New England Journal of Medicine
Published
2026-10-14
DOI
https://doi.org/10.1056/nejmoa2606208
Citations
1
Primary Topic
Acute Lymphoblastic Leukemia research
Type
article
Field-Weighted Citation Impact
6.10

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article

Ponatinib–Blinatumomab or Imatinib–Chemotherapy for Adult Ph-Positive ALL

Monica Bocchia, Daniele Giovanni Mattei, Michela Ansuinelli, Renato Bassan et al.
1 citations
New England Journal of Medicine
Acute Lymphoblastic Leukemia research
6.10
article

Ponatinib–Blinatumomab or Imatinib–Chemotherapy for Adult Ph-Positive ALL

Monica Bocchia, Daniele Giovanni Mattei, Michela Ansuinelli, Renato Bassan, Mario Luppi, Mariangela Di Trani, Robin Foà, Nicola Fracchiolla, Antonella Cucca, Paola Fazi, Francesca Kaiser, Silvia Imbergamo, Elisabetta Todisco, Paolo Fabio Fiumara, Federico Mosna, Cinzia Maugeri, Sara Butera, Matteo Leoncin, Erika Borlenghi, Mario Annunziata, Barbara Scappini, Monica Messina, Sara Mastaglio, Sabina Chiaretti, Chiara M. Cattaneo, Alfonso Piciocchi, Marco Cerrano, Martina Rachele Marino, Federico Lussana, Monia Lunghi, Claudio Romani, Alessandro Rambaldi, Patrizia Zappasodi, Ilaria Tanasi, Giulia Lucco Navei, Eleonora De Bellis, Massimiliano Bonifacio, Claudia Basilico, Prassede Salutari, Crescenza Pasciolla, Catello Califano, Deborah Cardinali, Massimo Vincenzo Martino, Bianca Serio, Ferdinando Porretto, Antonino Mulè, Lara Pochintesta, Matteo Giovanni Della Porta, Stefano Soddu, Cristina Skert, Giuseppe Rodolfo Nunziata, Caterina Alati, Loredana Elia, Giada Almici, Maria Paola Martelli, Patrizia Chiusolo, Valentina Mancini
article en
1 citations

Abstract

BACKGROUND: The outcome of Philadelphia-positive acute lymphoblastic leukemia (Ph-positive ALL) has greatly improved with the use of tyrosine kinase inhibitors and immunotherapy. METHODS: In this trial, we randomly assigned adult patients with Ph-positive ALL in a 2:1 ratio to receive ponatinib plus blinatumomab (intervention group) or imatinib plus chemotherapy (control group) as frontline treatment. A crossover to the intervention group was allowed for patients with persistence or reappearance of measurable residual disease in the control group. The primary end point was event-free survival. RESULTS: A total of 236 patients underwent randomization: 158 to the intervention group and 78 to the control group. The median age of the patients was 55 years (range, 24 to 82). At a median follow-up of 23.7 months, the estimated 24-month event-free survival was 86% in the intervention group and 67% in the control group (P<0.001). Survival with no measurable residual disease was 68% and 42%, respectively. At the end of induction, a complete hematologic response was observed in 94% of the patients in the intervention group and in 79% of those in the control group. After blinatumomab consolidation, a molecular response was observed in 71% and 49% of the patients, respectively. After crossover to the intervention group, 20 of 31 patients (64%) had a molecular response. Overall survival was 90% in the intervention group and 85% in the control group. The cumulative incidence of relapse was 5% and 13%, respectively. As of this report, only 19% of the patients in the intervention group had undergone hematopoietic stem-cell transplantation after having had a first complete hematologic response. CONCLUSIONS: In this phase 3 trial, a frontline chemotherapy-free targeted and immunotherapeutic approach was superior to the use of imatinib and chemotherapy. (Funded by Associazione Italiana per la Ricerca sul Cancro and others; GIMEMA ALL2820 ClinicalTrials.gov number, NCT04722848.).

New England Journal of MedicineVol. 395(15)
University of Siena (IT), University of Verona (IT), University of Modena and Reggio Emilia (IT), Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT), Humanitas University (IT), University of Padua (IT), Vita-Salute San Raffaele University (IT), University of Milan (IT), Ospedale di Circolo e Fondazione Macchi (IT), Agostino Gemelli University Polyclinic (IT), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT), Ospedale Antonio Cardarelli (IT), Azienda Ospedaliera di Perugia (IT), Ospedale di Bolzano (IT), Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT), Azienda ospedaliera "Bianchi-Melacrino-Morelli" (IT), Ospedale Vincenzo Cervello (IT), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Ospedale Papa Giovanni XXIII (IT), Azienda Ospedaliera S.Giuseppe Moscati (IT), Fondazione Gimema Onlus (IT), Azienda Ospedaliero-Universitaria Careggi (IT), Ospedale di Circolo di Busto Arsizio (IT), Azienda Socio Sanitaria Territoriale Lariana (IT), Istituto Tumori Bari (IT), Ospedali Riuniti San Giovanni di Dio e Ruggi d'Aragona (IT), Azienda Ospedaliera Universitaria Senese (IT), Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo (IT), Guglielmo da Saliceto Hospital (IT), Ospedale dell' Angelo (IT), Azienda USL di Pescara (IT), Policlinico San Matteo Fondazione (IT), Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo (IT), IRCCS Humanitas Research Hospital (IT), La Maddalena (IT), Azienda Ospedaliera G. Brotzu (IT), Azienda sanitaria universitaria Giuliano Isontina (IT), Sapienza University of Rome (IT)
Associazione Italiana per la Ricerca sul Cancro
Good health and well-being
Openalex Percentile: Top 3%
Acute Lymphoblastic Leukemia research
6.10
DOISourceOpenAlex
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