• Sumit Gupta, Rachel E Rau, John A Kairalla, Karen R Rabin, Cindy Wang, Anne L Angiolillo, Sarah Alexander, Andrew J Carroll, Susan Conway, Lia Gore, Ilan Kirsch, Holly R Kubaney, Amanda M Li, Jennifer L McNeer, Olga Militano, Tamara P Miller, Yvonne Moyer, Maureen M O'Brien, Maki Okada, Shalini C Reshmi, Mary Shago, Elizabeth Wagner, Naomi Winick, Brent L Wood, Tara Haworth-Wright, Faraz Zaman, Gerhard Zugmaier, Sue Zupanec, Meenakshi Devidas, Stephen P Hunger, David T Teachey, Elizabeth A Raetz, and Mignon L Loh.
• From the Division of Haematology-Oncology (S.G., S.A., S.Z.), the Faculty of Medicine (S.G., S.A.), and the Department of Laboratory Medicine and Pathobiology, University of Toronto (M.S.), Toronto, and British Columbia Children's Hospital, University of British Columbia, Vancouver (A.M.L.) - all in Canada; Seattle Children's Hospital (R.E.R., T.H.-W., M.L.L.), the Ben Towne Center for Childhood Cancer and Blood Disorders Research and the Department of Pediatrics, Fred Hutchinson Cancer Center, University of Washington (R.E.R., M.L.L.), and Adaptive Biotechnologies (I.K.) - all in Seattle; the Department of Biostatistics, Colleges of Medicine, Public Health, and Health Professions, University of Florida, Gainesville (J.A.K., C.W., S.C.); the Division of Pediatric Hematology-Oncology, Texas Children's Cancer and Hematology Center, Baylor College of Medicine, Houston (K.R.R.), Children's Blood and Cancer Center and Dell Children's Medical Center of Central Texas, Austin (H.R.K.), and the Department of Pediatrics, Division of Pediatric Hematology-Oncology, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas (N.W.) - all in Texas; Servier Pharmaceuticals, Boston (A.L.A.); the Department of Genetics, University of Alabama at Birmingham, Birmingham (A.J.C.); Children's Hospital Colorado and the University of Colorado School of Medicine, Aurora (L.G., M.M.O.); the Division of Pediatric Hematology-Oncology, University of Utah, Primary Children's Hospital, Salt Lake City (J.L.M.); the Children's Oncology Group, Monrovia (O.M.), the Department of Pediatric Hematology-Oncology, MemorialCare Miller Children's and Women's Hospital Long Beach, Long Beach (M.O.), the Department of Pathology and Laboratory Medicine, Children's Hospital of Los Angeles, Los Angeles (B.L.W.), and Amgen, Thousand Oaks (F.Z.) - all in California; the Department of Pediatrics, Emory University School of Medicine, Atlanta (T.P.M.); the Steve and Cindy Rasmussen Institute for Genomic Medicine and the Biopathology Center, Nationwide Children's Hospital (S.C.R.) and the Biopathology Center and Children's Oncology Group Biospecimen Bank, Nationwide Children's Hospital (Y.M., E.W.) - both in Columbus, OH; Amgen Research, Munich, Germany (G.Z.); the Department of Global Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, TN (M.D.); the Department of Pediatrics and the Center for Childhood Cancer Research, Children's Hospital of Philadelphia, and the Perelman School of Medicine, University of Pennsylvania - both in Philadelphia (S.P.H., D.T.T.); and the Department of Pediatrics and Perlmutter Cancer Center, NYU Langone Health, New York (E.A.R.).
• N. Engl. J. Med. 2024 Dec 7.

BackgroundB-cell acute lymphoblastic leukemia (B-cell ALL) is the most common childhood cancer. Despite a high overall cure rate, relapsed B-cell ALL remains a leading cause of cancer-related death among children. The addition of the bispecific T-cell engager molecule blinatumomab (an anti-CD19 and anti-CD3 single-chain molecule) to therapy for newly diagnosed standard-risk (as defined by the National Cancer Institute) B-cell ALL in children may improve outcomes.MethodsWe conducted a phase 3 trial involving children with newly diagnosed standard-risk B-cell ALL who had an average or high risk of relapse. Patients were randomly assigned to receive chemotherapy alone or chemotherapy plus two nonsequential 28-day cycles of blinatumomab. The primary end point was disease-free survival.ResultsThe data and safety monitoring committee reviewed the results from the first interim efficacy analysis, which included 1440 patients who had undergone randomization (722 to chemotherapy alone and 718 to blinatumomab and chemotherapy) and recommended early termination of randomization. At a median follow-up of 2.5 years, the estimated 3-year disease-free survival (±SE) was 96.0±1.2% with blinatumomab and chemotherapy and 87.9±2.1% with chemotherapy alone (difference in restricted mean survival time, 72 days; 95% confidence interval, 36 to 108; P<0.001 by stratified log-rank test). The estimated 3-year disease-free survival among patients with an average relapse risk was 97.5±1.3% with blinatumomab and chemotherapy and 90.2±2.3% with chemotherapy alone; among those with a high relapse risk, the corresponding values were 94.1±2.5% and 84.8±3.8%. Cytokine release syndrome, seizures, and sepsis of grade 3 or higher were rare during blinatumomab cycles, but the overall incidence of nonfatal sepsis and catheter-related infections was significantly higher among patients with an average relapse risk who had been assigned to receive blinatumomab and chemotherapy than among those assigned to receive chemotherapy alone.ConclusionsAdding blinatumomab to combination chemotherapy in patients with newly diagnosed childhood standard-risk B-cell ALL of average or high risk of relapse significantly improved disease-free survival. (Funded by the National Institutes of Health and others; AALL1731 ClinicalTrials.gov number, NCT03914625.).Copyright © 2024 Massachusetts Medical Society.

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