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Ajay K. Nooka, MD, MPH, FACP, Director of the Myeloma Program at the Emory University School of Medicine, discusses topline results from the MonumenTAL-6 clinical trial testing Tecvayli (teclistamab) in adults with relapsed/refractory multiple myeloma (RRMM). MM is a rare blood cancer characterized by the expansion of malignant plasma cells in the bone marrow associated with excessive production of monoclonal immunoglobulins in blood and urine. Individuals with multiple myeloma develop significant osteolytic bone lesions and have immunodeficiency that compromise their longevity and quality of life. The exact underlying cause of disease is currently unknown. Most patients with MM require multiple lines of therapy as patients are prone to the cancer relapsing and/or be refractory to initial therapies. Recently, positive topline results from the three-arm investigational phase 3 MonumenTAL-6 clinical trial (NCT06208150) were presented. The study evaluated teclistamab plus Talvey (talquetamab) (Tec-Tal) or talquetamab plus pomalidomide (Tal-P) in adult patients with relapsed/refractory MM who received 1 to 4 prior lines of therapy, including an anti-CD38 antibody and lenalidomide. Teclistamab is a first-in-class, bispecific T-cell engager antibody therapy designed to activate the immune system by binding to the CD3 receptor and the B-cell maturation antigen (BCMA) that are expressed on T-cells and multiple myeloma cells. The treatment first received accelerated approval from the US Food and Drug Administration (FDA) in October 2022. Talquetamab is a bispecific T-cell engaging antibody designed to bind to the CD3 receptor and G protein-coupled receptor class C group 5 member D (GPRC5D). The treatment first received accelerated approval from the U.S. FDA in August 2023. In the MonumenTAL-6 study, both regimens met the primary endpoint of progression free survival (PFS), demonstrating statistically significant and clinically meaningful improvements versus standard of care. Risk of progression or death was reduced in the Tec-Tal arm by 89% and 73% in the Tal-P arm. Additionally, the overall safety profiles for the Tec-Tal and Tal-P treatment arms were consistent with the known safety profiles of each monotherapy. CHAPTERS Introduction 00:00 MonumenTAL-6 Clinical Trial Key Results 1:07 Importance of Targeted Approach 6:05 Patients Most Likely to Benefit 7:06 How This Changes the Treatment Landscape 7:39 Treatment Toxicities 8:27

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