Mechanistic Rationale and Combination Strategies in Multiple Myeloma

In this segment on early relapse multiple myeloma, Luciano Costa asks Muhamed Baljevic to outline the mechanistic rationale for combining BCMA-directed bispecific antibodies with anti-CD38 therapy. Dr. Baljevic explains that bispecific antibodies promote T-cell redirection and activation against myeloma cells, while anti-CD38 therapy may enhance immune modulation by depleting immunosuppressive cell populations, including regulatory T cells. This complementary activity may contribute to a more favorable immune environment and potential synergy between the two approaches. Building on this, he interprets efficacy findings from MajesTEC-3, noting that outcomes such as depth of response and progression-free survival appear improved relative to historical standards. He emphasizes that these results should be considered within the broader treatment landscape, where evolving combination strategies aim to optimize disease control earlier in relapse. Overall, the discussion highlights how biologic rationale and clinical data together inform treatment approaches in multiple myeloma.