Dr Richter on the Current State of Bispecific Antibodies in Multiple Myeloma

Joshua Richter, MD, associate professor, medicine, Division of Hematology and Medical Oncology, the Tisch Cancer Institute, director, Multiple Myeloma, the Blavatnik Family Chelsea Medical Center, Mount Sinai, discusses how bispecific antibodies fit into the current treatment armamentarium for patients with multiple myeloma, highlighting his presentation from the 41st Annual CFS®.

Within the realm of multiple myeloma relapse scenarios, a dichotomy exists: early relapse, which occurs after 1 to 3 prior lines of therapy, and late relapse, which occurs after 4 or more prior lines of therapy, Richter begins. Early relapse typically happens after the application of classical agents, such as CD38 monoclonal antibodies, proteasome inhibitors, and immunomodulatory drugs, he states. However, treatment options for late-line relapses have been notably shaped by T-cell redirecting therapies, Richter explains. A particular focus has been directed toward bispecific antibodies, which are distinguished by their dual arms, Richter notes. One arm extends to CD3, which is present on all T cells, and the other targets a specific antigen on the myeloma cell, he adds.

The prominence of bispecific antibodies is underscored by the fact that approximately 80% of patients with myeloma in the United States are treated within the community setting, Richter continues. This underscores a significant demand for active agents that don't necessitate administration exclusively within academic centers, he says. Richter highlights that his presentation delved into key classes of bispecific agents. Among BCMA-targeted bispecific antibodies are teclistamab-cqyv (Tecvayli), elranatamab-bcmm (Elrexfio), and linvoseltamab (REGN5458). Additionally, non–BCMA-targeting bispecific antibodies, such as talquetamab-tgvs (Talvey) and forimtamig, which both target GPRC5D, and cevostamab (RG 6160), which targets FcRH5, were explored, Richter emphasizes. These agents exhibit high levels of activity in patients with multiple myeloma and are accompanied by a distinctive set of toxicities akin to those seen with CAR T-cell therapies. When administering these agents, consideration is given to cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, he emphasizes.

Ongoing studies are exploring the combination of bispecific antibodies with CD38 antibodies, such as daratumumab. Additionally, the phase 1/2 RedirecTT-1 study (NCT04586426) is investigating the synergistic potential of combining 2 bispecific antibodies, talquetamab and teclistamab, he continues. This comprehensive exploration of bispecific antibodies within the multiple myeloma treatment paradigm underscores their pivotal role in addressing treatment challenges, offering new avenues for patients in diverse settings, Richter concludes.