Sabina Chiaretti, Alfonso Piciocchi, Cristina Skert, Matteo Leoncin, Erika Borlenghi, Chiara Cattaneo, Mariangela Di Trani, Loredana Elia, Giada Almici, Deborah Cardinali, Francesca Kaiser, Federico Lussana, Paolo Fabio Fiumara, Cinzia Maugeri, Caterina Alati, Massimo Martino, Michela Ansuinelli, Giulia Lucco Navei, Daniele Mattei, Stefano Soddu, Monica Messina, Martina R Marino, Valentina Mancini, Patrizia Chiusolo, Barbara Scappini, Maria P Martelli, Prassede Salutari, Marco Cerrano, Bianca Serio, Antonella Cucca, Mario Luppi, Lara Pochintesta, Crescenza Pasciolla, Claudio Romani, Federico Mosna, Massimiliano Bonifacio, Ilaria Tanasi, Nicola S Fracchiolla, Monica Bocchia, Silvia Imbergamo, Catello Califano, Giuseppe R Nunziata, Mario Annunziata, Antonino Mulé, Patrizia Zappasodi, Sara Mastaglio, Sara Butera, Matteo G Della Porta, Ferdinando Porretto, Monia Lunghi, Eleonora De Bellis, Elisabetta Todisco, Claudia M Basilico, Paola Fazi, Alessandro Rambaldi, Renato Bassan, Robin Foà
{"title":"Ponatinib-Blinatumomab or Imatinib-Chemotherapy for Adult Ph-Positive ALL.","authors":"Sabina Chiaretti, Alfonso Piciocchi, Cristina Skert, Matteo Leoncin, Erika Borlenghi, Chiara Cattaneo, Mariangela Di Trani, Loredana Elia, Giada Almici, Deborah Cardinali, Francesca Kaiser, Federico Lussana, Paolo Fabio Fiumara, Cinzia Maugeri, Caterina Alati, Massimo Martino, Michela Ansuinelli, Giulia Lucco Navei, Daniele Mattei, Stefano Soddu, Monica Messina, Martina R Marino, Valentina Mancini, Patrizia Chiusolo, Barbara Scappini, Maria P Martelli, Prassede Salutari, Marco Cerrano, Bianca Serio, Antonella Cucca, Mario Luppi, Lara Pochintesta, Crescenza Pasciolla, Claudio Romani, Federico Mosna, Massimiliano Bonifacio, Ilaria Tanasi, Nicola S Fracchiolla, Monica Bocchia, Silvia Imbergamo, Catello Califano, Giuseppe R Nunziata, Mario Annunziata, Antonino Mulé, Patrizia Zappasodi, Sara Mastaglio, Sara Butera, Matteo G Della Porta, Ferdinando Porretto, Monia Lunghi, Eleonora De Bellis, Elisabetta Todisco, Claudia M Basilico, Paola Fazi, Alessandro Rambaldi, Renato Bassan, Robin Foà","doi":"10.1056/NEJMoa2606208","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The outcome of Philadelphia-positive acute lymphoblastic leukemia (Ph-positive ALL) has greatly improved with the use of tyrosine kinase inhibitors and immunotherapy.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"395 15","pages":"1483-1494"},"PeriodicalIF":84.5000,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"New England Journal of Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1056/NEJMoa2606208","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
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.).
期刊介绍：
The New England Journal of Medicine (NEJM) stands as the foremost medical journal and website worldwide. With an impressive history spanning over two centuries, NEJM boasts a consistent publication of superb, peer-reviewed research and engaging clinical content. Our primary objective revolves around delivering high-caliber information and findings at the juncture of biomedical science and clinical practice. We strive to present this knowledge in formats that are not only comprehensible but also hold practical value, effectively influencing healthcare practices and ultimately enhancing patient outcomes.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
