Molecular features and outcomes for patients receiving elranatamab for relapsed or refractory multiple myeloma in MagnetisMM-1.

person Michael H. Tomasson Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA info_outline Michael H. Tomasson, Nizar J. Bahlis, Caitlin Costello, Noopur S. Raje, Moshe Y. Levy, Bhagirathbhai R. Dholaria, Melhem M. Solh, Michael A. Damore, Sibo Jiang, Tao Xie, Cynthia Basu, Athanasia Skoura, Edward Michael Chan, Suzanne Trudel, Andrzej J. Jakubowiak, Cristina Gasparetto, Michael Chu, Andrew Peter Dalovisio, Michael Sebag, Alexander M. Lesokhin

Authors person Michael H. Tomasson Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA info_outline Michael H. Tomasson, Nizar J. Bahlis, Caitlin Costello, Noopur S. Raje, Moshe Y. Levy, Bhagirathbhai R. Dholaria, Melhem M. Solh, Michael A. Damore, Sibo Jiang, Tao Xie, Cynthia Basu, Athanasia Skoura, Edward Michael Chan, Suzanne Trudel, Andrzej J. Jakubowiak, Cristina Gasparetto, Michael Chu, Andrew Peter Dalovisio, Michael Sebag, Alexander M. Lesokhin Organizations Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada, Moores Cancer Center, University of California San Diego, La Jolla, CA, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, Department of Medical Oncology, Baylor Scott and White Health, Dallas, TX, Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, Nashville, TN, Blood and Marrow Transplant Group of Georgia, Northside Hospital, Atlanta, GA, Oncology Research and Development, Pfizer, San Diego, CA, Early Clinical Development, Pfizer, San Diego, CA, Oncology Research and Development, Pfizer, La Jolla, CA, Early Clinical Development, Pfizer, Collegeville, PA, Oncology Research and Development, Pfizer, South San Francisco, CA, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, Department of Medicine, University of Chicago Medical Center, Chicago, IL, Department of Medicine, Duke University Cancer Institute, Durham, NC, Cross Cancer Institute, Edmonton, Edmonton, AB, Canada, Department of Hematology and Oncology, Ochsner Health, Jefferson, LA, Cedars Cancer Center, McGill University Health Center, Montreal, QC, Canada, Division of Hematology and Oncology, Memorial Sloan Kettering Cancer Center/Weill Cornell Medical College, New York, NY Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Pfizer Background: Multiple myeloma (MM) is a plasma cell dyscrasia that expresses B-cell maturation antigen (BCMA). Elranatamab (PF-06863135), a BCMA x CD3 bispecific antibody, redirects the T-cell mediated immune response against MM. MagnetisMM-1 (NCT03269136) is the Phase 1 study evaluating safety, pharmacokinetics (PK), pharmacodynamics, and efficacy of elranatamab for patients (pts) with relapsed or refractory MM. Methods: Elranatamab was given subcutaneously at doses 80–1000 µg/kg weekly or every 2 weeks. Treatment-emergent adverse events (TEAEs) were graded by National Cancer Institute Common Terminology Criteria for Adverse Events (v4.03), whereas cytokine release syndrome (CRS) was assessed by criteria of American Society for Transplantation and Cellular Therapy. PK and cytokines were analyzed over time. Bone marrow aspirates were used for cytogenetic analysis, whole exome sequencing, and minimal residual disease (MRD). Clinical response and MRD (with sensitivity of 1×10 -5 by next generation sequencing) were assessed by International Myeloma Working Group criteria. Results: 55 pts received elranatamab at efficacious doses ≥215 μg/kg as of September 30, 2022. Pts had median age of 64 years (range 42-80), median of 5 prior regimens (range 2-14), 91% were triple-class refractory, 29% had high cytogenetic risk, and 24% received prior BCMA-targeted therapy. The most common TEAEs included CRS, injection site reaction, neutropenia, anemia, lymphopenia, and thrombocytopenia. Premedication and 1-step priming mitigated CRS. Elranatamab showed linear PK. Genetic alterations potentially relevant to molecular pathogenesis of MM were identified and included functional mutations in KRAS , NRAS , and TP53 . With median follow-up of 12.0 months (range 0.3-32.3), objective response rate (ORR) was 64% (95% CI 50-75%) with 56% of pts (31/55) achieving very good partial response (VGPR) or better and 38% of pts (21/55) achieving complete response (CR) or better. Among 13 pts with prior BCMA-targeted therapy, 54% (7/13) achieved response including 46% (6/13) with VGPR or better. All 13 MRD-evaluable pts with confirmed CR or better and dominant clone sequence at baseline achieved MRD negativity, including 2 patients with ongoing stringent CR beyond 2 years. Median duration of response (DOR) was 17.1 months (n = 35; 95% CI 11.1-NE). Median progression-free survival (PFS) was 11.8 months (n = 55; 95% CI 6.0-19.1), and median overall survival (OS) was 21.2 months (n = 55; 95% CI 10.9-NE). Conclusions: Elranatamab induced durable clinical and molecular responses with an acceptable safety profile for pts with relapsed or refractory MM. The ORR was 64% with more than half of these pts (38%) achieving CR or better, and 100% of evaluable pts achieved MRD negativity. These results, along with emerging evidence for both PFS and OS, support the clinical activity of elranatamab for pts with MM. Clinical trial information: NCT03269136.

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