Blinatumomab for Replacing Chemotherapy in Pediatric Acute Lymphoblastic Leukemia

BACKGROUND: Blinatumomab, a bispecific T-cell engager targeting the CD19 antigen on B cells, may offer an option to safely replace cycles of traditional chemotherapy in pediatric patients with newly diagnosed high-risk B-cell acute lymphoblastic leukemia (ALL). METHODS: We randomly assigned, in a 1:1 ratio, children with high-risk B-cell ALL to receive two cycles of blinatumomab (blinatumomab group) or two cycles of chemotherapy (control group) after consolidation. The primary end point was event-free survival as evaluated in a time-to-event analysis; the duration of event-free survival was defined as the time from randomization to the first event among resistance to protocol treatment, relapse, second cancer, or death from any cause. Our primary objective was to evaluate whether the 4-year event-free survival would be 10 percentage points higher in the blinatumomab group than in the control group. RESULTS: Overall, 709 of 768 eligible patients (92.3%) underwent randomization; 358 were assigned to the blinatumomab group and 351 to the control group. A planned interim analysis at a median follow-up of 2.9 years showed an estimated 4-year event-free survival of 83.0% (95% confidence interval [CI], 77.4 to 87.4) in the blinatumomab group and 70.3% (95% CI, 63.8 to 75.9) in the control group (P = 0.0002 in an intention-to-treat analysis). The estimated hazard ratio for a primary end-point event (blinatumomab vs. control) was 0.51 (95% CI, 0.35 to 0.73) as assessed with a Cox model. Infection related to the trial treatment occurred in 23.9% of patients in the blinatumomab group and in 69.4% of those in the control group (P<0.001). Life-threatening adverse events occurred in 2 patients (0.5%) in the blinatumomab group, including one (in 0.3%) that was fatal, and in 16 patients (4.7%) in the control group. Neurotoxic events were reported in 12.0% and 3.2%, respectively (P<0.001). Cytokine release syndrome of grade 2 or higher occurred in 1.1% of patients in the blinatumomab group. CONCLUSIONS: In children with newly diagnosed high-risk B-cell ALL, replacement of two cycles of highly toxic conventional chemotherapy with blinatumomab resulted in a significantly greater percentage of patients with event-free survival at 4 years. (Funded by Deutsche Krebshilfe and others; AIEOP-BFM ALL 2017 EudraCT number, 2016-001935-12; EU Clinical Trials number, 2023-509856-32-00; and ClinicalTrials.gov number, NCT03643276.).

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Publication Details

Journal
New England Journal of Medicine
Published
2026-09-16
DOI
https://doi.org/10.1056/nejmoa2604166
Citations
1
Primary Topic
Acute Lymphoblastic Leukemia research
Type
article
Field-Weighted Citation Impact
7.59

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article

Blinatumomab for Replacing Chemotherapy in Pediatric Acute Lymphoblastic Leukemia

Valentino Conter, Maria Caterina Putti, Claudia Rössig, Draga Barbaric et al.
1 citations
New England Journal of Medicine
Acute Lymphoblastic Leukemia research
7.59
article

Blinatumomab for Replacing Chemotherapy in Pediatric Acute Lymphoblastic Leukemia

Valentino Conter, Maria Caterina Putti, Claudia Rössig, Draga Barbaric, Julia Alten, Laura Rachele Bettini, Gerhard Zugmaier, Patrick Hundsdörfer, Luciano Dalla‐Pozza, Arndt Borkhardt, Jan Starý, Luciana Vinti, Michaela Vossen‐Gajcy, Barbara Buldini, Andrea Biondi, Jean‐Pierre Bourquin, Carmelo Rizzari, Nicole Bodmer, Anja Möricke, Lucie Šrámková, Franca Fagioli, Monika Brüggemann, Faraz Zaman, Giovanni Cazzaniga, Fiona Poyer, Sarah Elitzur, Andishe Attarbaschi, Rolf Köhler, Martin Zimmermann, Arend von Stackelberg, Rosanna Parasole, Franco Locatelli, Grazia Fazio, Gunnar Cario, Martin Schrappe, Anke Bergmann, Maria Grazia Valsecchi, Daniela Silvestri, Alexandra Kolenova, Martin Stanulla
article en
1 citations

Abstract

BACKGROUND: Blinatumomab, a bispecific T-cell engager targeting the CD19 antigen on B cells, may offer an option to safely replace cycles of traditional chemotherapy in pediatric patients with newly diagnosed high-risk B-cell acute lymphoblastic leukemia (ALL). METHODS: We randomly assigned, in a 1:1 ratio, children with high-risk B-cell ALL to receive two cycles of blinatumomab (blinatumomab group) or two cycles of chemotherapy (control group) after consolidation. The primary end point was event-free survival as evaluated in a time-to-event analysis; the duration of event-free survival was defined as the time from randomization to the first event among resistance to protocol treatment, relapse, second cancer, or death from any cause. Our primary objective was to evaluate whether the 4-year event-free survival would be 10 percentage points higher in the blinatumomab group than in the control group. RESULTS: Overall, 709 of 768 eligible patients (92.3%) underwent randomization; 358 were assigned to the blinatumomab group and 351 to the control group. A planned interim analysis at a median follow-up of 2.9 years showed an estimated 4-year event-free survival of 83.0% (95% confidence interval [CI], 77.4 to 87.4) in the blinatumomab group and 70.3% (95% CI, 63.8 to 75.9) in the control group (P = 0.0002 in an intention-to-treat analysis). The estimated hazard ratio for a primary end-point event (blinatumomab vs. control) was 0.51 (95% CI, 0.35 to 0.73) as assessed with a Cox model. Infection related to the trial treatment occurred in 23.9% of patients in the blinatumomab group and in 69.4% of those in the control group (P<0.001). Life-threatening adverse events occurred in 2 patients (0.5%) in the blinatumomab group, including one (in 0.3%) that was fatal, and in 16 patients (4.7%) in the control group. Neurotoxic events were reported in 12.0% and 3.2%, respectively (P<0.001). Cytokine release syndrome of grade 2 or higher occurred in 1.1% of patients in the blinatumomab group. CONCLUSIONS: In children with newly diagnosed high-risk B-cell ALL, replacement of two cycles of highly toxic conventional chemotherapy with blinatumomab resulted in a significantly greater percentage of patients with event-free survival at 4 years. (Funded by Deutsche Krebshilfe and others; AIEOP-BFM ALL 2017 EudraCT number, 2016-001935-12; EU Clinical Trials number, 2023-509856-32-00; and ClinicalTrials.gov number, NCT03643276.).

New England Journal of MedicineVol. 395(11)
Università Cattolica del Sacro Cuore (IT), St. Jude Children's Research Hospital (US), Amgen (United States) (US), University of Padua (IT), Philipps University of Marburg (DE), Tel Aviv University (IL), Charles University (CZ), Heidelberg University (DE), University of Würzburg (DE), Children's Hospital at Westmead (AU), UNSW Sydney (AU), Christian-Albrechts-Universität zu Kiel (DE), Medizinische Hochschule Hannover (DE), University Hospital in Motol (CZ), University Hospital Münster (DE), Schneider Children's Medical Center (IL), Azienda Ospedaliera San Gerardo (IT), Institute of Human Genetics (PL), Amgen (Germany) (DE), Bambino Gesù Children's Hospital (IT), St Anna Children's Hospital (AT), Santobono Children's Hospital (IT), Sydney Children's Hospital (AU), Universitätsklinikum Würzburg (DE), University Children's Hospital Zurich (CH), Ospedale Regina Margherita (IT), Azienda Ospedale - Università Padova (IT), University of the Sacred Heart (JP), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Helios Hospital Berlin-Buch (DE), Città della Speranza Foundation (IT), Heinrich Heine University Düsseldorf (DE), University of Turin (IT), University of Milano-Bicocca (IT), Comenius University Bratislava (SK), Charité - Universitätsmedizin Berlin (DE)
Fondazione AIRC per la ricerca sul cancro ETS, Fondazione Città della Speranza, Ministerstvo Zdravotnictví Ceské Republiky, Israel Cancer Association, Deutsche Krebshilfe
Openalex Percentile: Top 2%
Acute Lymphoblastic Leukemia research
7.59
DOISourceOpenAlex
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