Treatment options for multiple myeloma continue to expand. Newer therapeutic targets include BCMA, GPRC5D, FCRH5, and cereblon E3 ligase. CAR T-cell therapies and bispecific T-cell engagers are already available or in development for these and other targets.

The field of multiple myeloma has evolved rapidly, and our patients now have access to innovative therapies, including CAR T cells and bispecific T-cell engagers targeting BCMA and GPRC5D. The BCMA-directed CAR T-cell therapies with US Food and Drug Administration (FDA) approval in multiple myeloma are ciltacabtagene autoleucel after at least 1 line of therapy and idecabtagene vicleucel after 2 or more lines of therapy.

The following 3 bispecific T-cell engagers have accelerated approval from the FDA: teclistamab-cqyv and elranatamab-bcmm, which target BCMA, and talquetamab-tgvs, which targets GPRC5D. All are indicated after 4 or more lines of therapy. Other bispecific T-cell engagers, such as cevostamab (targeting FCRH5) and linvoseltamab (targeting BCMA), are in development.

These treatment advances have led to marked benefits for patients with advanced multiple myeloma. For example, in clinical trials, response rates have ranged from 63% with teclistamab-cqyv to 97.9% with ciltacabtagene autoleucel. Another emerging area is cereblon E3 ligase modulation; iberdomide and mezigdomide are 2 agents that are far along in development.

Unfortunately, patients with high-risk multiple myeloma—a stratification that includes those with particular genetic profiles, stage III disease, and clinically aggressive disease—still have poor outcomes. However, we have seen significant improvements as we use newer agents earlier in treatment.

CAR T-cell therapies and bispecific T-cell engagers can have challenging adverse-event profiles that require expertise in management. Cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), in particular, can occur in patients receiving either CAR T cells or bispecific T-cell engagers. These adverse events have limited the use of CAR T-cell and bispecific T-cell engager therapies in community-based clinical settings that lack the resources to manage them as quickly and efficiently as academic medical centers. Ongoing studies are focused on reducing the incidence and severity of CRS and ICANS. We hope that, in the future, these agents can be given to a broader patient population.

Infections are also a concern with bispecific T-cell engagers, but appropriate management can help mitigate their severity. That said, we have seen some uncommon adenovirus and cytomegalovirus infections, so being aware of the risk of and frequently monitoring patients for infections are important aspects of care. One strategy to try to reduce infectious complications might be administering bispecific T-cell engagers less frequently after an initial treatment period.

Over time, some patients with multiple myeloma lose BCMA as a target. In other patients, circulating BCMA increases, which can bind drugs and reduce the tumor response. Ongoing trials are evaluating combination therapies targeting BCMA and other targets. For example, the phase 1b RedirecTT-1 trial reported that the combination of teclistamab-cqyv and talquetamab-tgvs resulted in a 92% response rate at the recommended phase 2 regimen. There are also trials evaluating combinations with CAR T-cell therapies. These studies are only in phase 1, but we are eagerly awaiting additional data. Ultimately, we hope to leverage these technologies so that more patients can benefit.