Up-front blinatumomab improves MRD clearance and outcome in adult Ph– B-lineage ALL: the GIMEMA LAL2317 phase 2 study
Abstract
Abstract The Gruppo Italiano Malattie EMatologiche dell’Adulto (GIMEMA) Leucemia Acuta Linfoblastica (LAL) 2317 protocol investigated the frontline chemotherapy-blinatumomab combination in adult Philadelphia chromosome/BCR::ABL1 rearrangement–negative (Ph–) CD19+ B-lineage acute lymphoblastic leukemia (B-ALL) to improve minimal residual disease (MRD) response and clinical outcome. Two cycles of IV blinatumomab were administered after chemotherapy cycles 3 and 6. The primary end point was the rate of molecular MRD negativity after blinatumomab 1. One hundred forty-nine patients were enrolled (median age, 41 years [range, 18-65]); 132 entered remission, 122 received blinatumomab, and 109 had a pre– and post–blinatumomab 1 MRD assessment. MRD negativity increased from 72% to 93% (P < .001) after blinatumomab, with 23 of 30 MRD-positive patients (73%) becoming MRD negative, fulfilling the primary end point. At a median follow-up of 38.1 months (range, 0.5-62.8), the median overall survival (OS) and disease-free survival (DFS) were not reached, and the estimated 3-year OS and DFS were 71% and 65%, respectively, with an excellent outlook for the patients aged 18 to 40 years who achieved an early MRD negativity (DFS, 92%). Pre-blinatumomab MRD predicted a worse outcome, especially in genetically high-risk patients. Notably, the 3-year survival of blinatumomab-treated patients was 82%. Survival and relapse rates were 91% and 15% in patients assigned to standard chemotherapy, 59% and 35% in patients assigned to hematopoietic stem cell transplantation, and 69% and 19% in transplant recipients, respectively. Blinatumomab toxicity was manageable, with only 8 permanent discontinuations. This chemotherapy-blinatumomab risk-oriented program yielded remarkable results that need further improvement in higher-risk patients displaying early MRD persistence. Blinatumomab should be considered as a standard component of induction/consolidation for adult Ph– B-ALL. This trial was registered at www.ClinicalTrials.gov as #NCT03367299.
Article Details
Authors (33)
Renato Bassan
4Ospedali Riuniti, Mestre-Venezia, Italy
Sabina Chiaretti
9Divisione di Ematologia, Dipartimento di Medicina Traslazionale e di Precisione, Sapienza Università di Roma, Roma, Italy
Irene Della Starza
1Sapienza University, Rome, Italy
Alessandra Santoro
4Division of Hematology and Bone Marrow Transplantation, Ospedali Riuniti Villa Sofia, Palermo, Italy
Orietta Spinelli
1ASST Papa Giovanni XXIII, Bergamo, Italy
Manuela Tosi
5Department of Oncology and Hematology, Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy
Loredana Elia
ematologia, Roma, Italy
Deborah Cardinali
1Sapienza University, Rome, Italy
Maria Stefania De Propris
1Sapienza University, Rome, Italy
Matteo Piccini
1SOD Ematologia, Università di Firenze, AOU Careggi, Firenze, Italy
Federico Lussana
1ASST Papa Giovanni XXIII, Bergamo, Italy
Mario Annunziata
8Hematology, Hospital “Antonio Cardarelli”, Napoli, Italy
Patrizia Chiusolo
6Section of Hematology, Department of Radiological and Hematological Sciences, Catholic University, Fondazione Policlinico Gemelli IRCCS, Rome, Italy
Patrizia Zappasodi
7Dipartimento di Oncoematologia, Fondazione IRCCS Policlinico San Matteo., Pavia, Italy
Erika Borlenghi
10ASST Spedali Civili of Brescia, Department of Hematology, Brescia, Italy
Matteo Leoncin
8UOC Ematologia, Azienda Ulss Serenissima, Ospedale dell'Angelo, Venezia, Italy
Catello Califano
29Hematology, Hospital “Andrea Tortora”, Pagani, Pagani, Italy
Monica Bocchia
1Hematology Unit, University of Siena, Siena, Italy
Francesco Di Raimondo
Francesco Grimaldi
7AOU Federico II, Dipartimento di Medicina Clinica e Chirurgia, Napoli, Italy
Mario Tiribelli
6Clinica Ematologica, Dipartimento di Medicina, Università degli Studi di Udine e Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy
Anna Candoni
33. Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto, Università di Modena e Reggio Emilia, AOU di Modena, Modena, Italy
Albana Lico
19Hematology Unit, Department of Hematology, San Bortolo Hospital, Vicenza, Italy
Ernesta Audisio
6SC Ematologia 2, AOU Città della Salute, Ospedale S.G: Battista Molinette, Torino, Italy
Monia Lunghi
15Division of Hematology, Department of Translational Medicine, AOU Maggiore della Carità, University of Eastern Piedmont, Novara, Italy
Anna Maria Mianulli
5Hematology, Infermi Hospital, Rimini, Italy
Mariangela Di Trani
1Sapienza University, Rome, Italy
Valentina Arena
Monica Messina
11GIMEMA Foundation, Data Center and Health Outcomes Research Unit, Rome, Italy
Alfonso Piciocchi
4GIMEMA, Rome, Italy
Paola Fazi
4GIMEMA, Rome, Italy
Alessandro Rambaldi
5University of Milan and Azienda Socio Sanitaria territorial Papa Giovanni XXIII, Bergamo, Italy, Department of Hematology-Oncology, Bergamo, Italy
Robin Foà
Department of Translational and Precision Medicine, Sapienza University, Rome