Dr Chari on the Evolving Role of Bispecific Antibodies and CAR T-Cell Therapy in Multiple Myeloma

Ajai Chari, MD, director, clinical research, Multiple Myeloma Program, UCSF Helen Diller Family Comprehensive Cancer Center, discusses the evolving role of bispecific antibodies and CAR T-cell therapies, such as ciltacabtagene autoleucel (cilta-cel; Carvykti), in the treatment of patients with multiple myeloma.

The emphasis on treating patients with multiple myeloma as quickly as possible has led to a shortcoming in thoughtfully using available agents in combinations and sequences, Chari begins. The FDA approvals of CAR T-cell therapies and bispecific antibodies has brought this concern to the forefront of oncologists’ minds, he says. Notably, CAR T-cell therapy should be used in patients with indolent disease that can wait for the manufacturing of therapy, and patients who cannot wait for therapy because of the status of their disease should receive off-the-shelf treatment with bispecific antibodies, Chari explains.

However, the effects of bispecific antibodies on antigen and genomic loss have yet to be determined, and it is unknown whether the targets of these agents are still expressed at protein and genomic levels following therapy, Chari emphasizes. Literature suggests that monoallelic loss at baseline prior to BCMA- or GPRC5D-directed therapy increases the potential for biallelic loss, Chari continues. Therefore, if a patient receives a BCMA- or GPRC5D-directed treatment in the frontline setting, it may be beneficial to switch targets for their subsequent therapies, he adds.

Furthermore, considerations regarding T-cell exhaustion and T-cell fitness are important. Chari emphasizes that patients should not receive a BCMA-directed bispecific antibody before treatment with cilta-cel because that treatment sequence is associated with a decline in progression-free survival (PFS) vs the PFS in BCMA-naïve patients who received cilta-cel. Overall, it continues to be important to avoid categorizing all pre-CAR T-cell therapy patients into one continuous segment and instead consider categories of pre-apheresis and post-apheresis, Chari continues. Candidates for cilta-cel must have T cells that are as viable as possible, Chari concludes.