Up-front blinatumomab improves MRD clearance and outcome in adult Ph– B-lineage ALL: the GIMEMA LAL2317 phase 2 study

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.

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Journal
Blood
Published
2025-02-26
DOI
https://doi.org/10.1182/blood.2024027500
Citations
28
Primary Topic
Acute Lymphoblastic Leukemia research
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article
Field-Weighted Citation Impact
52.60
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article

Up-front blinatumomab improves MRD clearance and outcome in adult Ph– B-lineage ALL: the GIMEMA LAL2317 phase 2 study

Valentina Arena, Anna Candoni, Renato Bassan, Francesco Grimaldi et al.
28 citations
Blood
Acute Lymphoblastic Leukemia research
52.60
article

Up-front blinatumomab improves MRD clearance and outcome in adult Ph– B-lineage ALL: the GIMEMA LAL2317 phase 2 study

Valentina Arena, Anna Candoni, Renato Bassan, Francesco Grimaldi, Mariangela Di Trani, Robin Foà, Orietta Spinelli, Paola Fazi, Monica Messina, Mario Tiribelli, Matteo Leoncin, Erika Borlenghi, Mario Annunziata, Francesco Di Raimondo, Monica Bocchia, Sabina Chiaretti, Alfonso Piciocchi, Patrizia Chiusolo, Alessandra Santoro, Federico Lussana, Monia Lunghi, Alessandro Rambaldi, Albana Lico, Patrizia Zappasodi, Irene Della Starza, Catello Califano, Deborah Cardinali, Matteo Piccini, Ernesta Audisio, Anna Maria Mianulli, Maria Stefania De Propris, Manuela Tosi, Loredana Elia
article en
28 citations

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.

BloodVol. 145(21)
University of Siena (IT), Università Cattolica del Sacro Cuore (IT), University of Bergamo (IT), University of Modena and Reggio Emilia (IT), Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT), University of Udine (IT), University of Milan (IT), Agostino Gemelli University Polyclinic (IT), University of Catania (IT), Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT), Ospedale Antonio Cardarelli (IT), Ospedale Vincenzo Cervello (IT), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Ospedale Papa Giovanni XXIII (IT), Azienda Unità Sanitaria Locale Della Romagna (IT), Fondazione Gimema Onlus (IT), Azienda Ospedaliero-Universitaria Careggi (IT), Istituto di Ematologia di Bologna (IT), Presidio Ospedaliero (IT), Ospedale Infermi di Rimini (IT), Policlinico Universitario di Catania (IT), Azienda Ospedaliera Universitaria Senese (IT), Associazione Italiana Ematologia Oncologia Pediatrica (IT), Ospedale dell' Angelo (IT), Policlinico San Matteo Fondazione (IT), Ospedale San Bortolo (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Piedmont University (US), University of Naples Federico II (IT), Sapienza University of Rome (IT)
Good health and well-being
Openalex Percentile: Top 0%
Acute Lymphoblastic Leukemia research
52.60
DOIOpen Access PDFOpenAlex
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