Dr Chari on Currently Available Bispecific Antibodies in Multiple Myeloma

Ajai Chari, MD, director, clinical research, Multiple Myeloma Program, UCSF Helen Diller Family Comprehensive Cancer Center, discusses the current landscape of bispecific antibodies in relapsed/refractory multiple myeloma.

The first 2 BCMA-targeted bispecific antibodies that were FDA approved for the treatment of patients with multiple myeloma were teclistamab-cqyv (Tecvayli), which was approved in October 2022, and elranatamab-bcmm (Elrexfio), which was approved in August 2023. Although the BCMA-directed class is one of the most crowded classes of bispecific antibodies, Chari explains that there are no major differences in efficacy and safety between these drugs. Therefore, when choosing which agent to treat a patient with, it is important to consider factors such as treatment convenience, schedule, and cost, Chari says, noting that it is beneficial for patients to have several available treatment choices. The bispecific antibody most recently approved for patients with relapsed/refractory multiple myeloma is the GPRC5D-targeted agent talquetamab-tgvs (Talvey), which received FDA approval for this population in August 2023, he explains.

Notably, agents that target GPRC5D are associated with similar efficacy outcomes and rates of cytokine release syndrome as those targeting BCMA, Chari expands. However, the differences between these targeted agents become more apparent when considering the agents’ toxicity profiles. BCMA-directed agents tend to lead to higher rates of infections than GPRC5D-directed agents with longer follow-up, Chari continues. These infections tend to be unusual, opportunistic infections, Chari says, adding that he encourages his colleagues to always be aware of the possibility of non-progression–related deaths when treating patients with BCMA-directed bispecific antibodies. If the primary cause of death in some patients is not disease progression, then the safety profiles of these agents should be further understood, according to Chari.

GPRC5D-targeted agents are associated with fewer infectious deaths, Chari notes. Instead, they may cause adverse effects (AEs) that affect patients’ skin and nails, and are also associated with oral toxicities, Chari explains. Skin rashes can be managed with steroids, but the most challenging AEs are the oral toxicities, which can manifest as taste loss, difficulty swallowing, and weight loss, he concludes.