Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults

Mark R. Litzow, Zhuoxin Sun, Ryan J. Mattison, Elisabeth M. Paietta, Kathryn G. Roberts, Yanming Zhang, Janis Racevskis, Hillard M. Lazarus, Jacob M. Rowe, Daniel A. Arber, Matthew J. Wieduwilt, Michaela Liedtke, Julie Bergeron, Brent L. Wood, Yaqi Zhao, Gang Wu, Ti Cheng Chang, Wenchao Zhang, Keith W. Pratz, Shira N. DinnerNoelle Frey, Steven D. Gore, Bhavana Bhatnagar, Ehab L. Atallah, Geoffrey L. Uy, Deepa Jeyakumar, Tara L. Lin, Cheryl L. Willman, Daniel J. DeAngelo, Shejal B. Patel, Michelle A. Elliott, Anjali S. Advani, Dimitrios Tzachanis, Pankit Vachhani, Rupali R. Bhave, Elad Sharon, Richard F. Little, Harry P. Erba, Richard M. Stone, Selina M. Luger, Charles G. Mullighan, Martin S. Tallman

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

BACKGROUND Many older adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have a relapse despite having a measurable residual disease (MRD)–negative complete remission with combination chemotherapy. The addition of blinatumomab, a bispecific T-cell engager molecule that is approved for the treatment of relapsed, refractory, and MRD-positive BCP-ALL, may have efficacy in patients with MRD-negative remission. METHODS In a phase 3 trial, we randomly assigned patients 30 to 70 years of age with BCR::ABL1-negative BCP-ALL (with:: indicating fusion) who had MRD-negative remission (defined as <0.01% leukemic cells in bone marrow as assessed on flow cytometry) after induction and intensification chemotherapy to receive four cycles of blinatumomab in addition to four cycles of consolidation chemotherapy or to receive four cycles of consolidation chemotherapy alone. The primary end point was overall survival, and relapse-free survival was a secondary end point. RESULTS The data and safety monitoring committee reviewed the results from the third efficacy interim analysis and recommended that they be reported. Complete remission with or without full count recovery was observed in 395 of 488 enrolled patients (81%). Of the 224 patients with MRD-negative status, 112 were assigned to each group. The characteristics of the patients were balanced between the groups. At a median follow-up of 43 months, an advantage was observed in the blinatumomab group as compared with the chemotherapy-only group with regard to overall survival (at 3 years: 85% vs. 68%; hazard ratio for death, 0.41; 95% confidence interval [CI], 0.23 to 0.73; P=0.002), and the 3-year relapse-free survival was 80% with blinatumomab and 64% with chemotherapy alone (hazard ratio for relapse or death, 0.53; 95% CI, 0.32 to 0.87). A higher incidence of neuropsychiatric events was reported in the blinatumomab group than in the chemotherapy-only group. CONCLUSIONS The addition of blinatumomab to consolidation chemotherapy in adult patients in MRD-negative remission from BCP-ALL significantly improved overall survival.

Original languageEnglish
Pages (from-to)320-333
Number of pages14
JournalNew England Journal of Medicine
Volume391
Issue number4
DOIs
StatePublished - Jul 25 2024

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