T cell redirecting bispecific antibodies for multiple myeloma: emerging therapeutic strategies in a changing treatment landscape

Abstract

In recent years, the treatment landscape of multiple myeloma has continued to evolve with the introduction of novel immunotherapies. This progress has translated to improved overall survival for patients, but an unmet need remains in the heavily pretreated and high-risk subsets of patients. Emerging immunotherapies in the form of CAR-T cell therapies have been approved for multiple myeloma. However, CAR-T cell therapy has logistical limitations and there is a need for immunotherapies that are readily available, safe, and effective in RRMM. Currently, pending approval, there are many “off the shelf” bispecific antibodies being developed that target BCMA, GPRC5D, FcRH5 and other cell surface proteins. Preliminary efficacy data has suggested that these bispecific antibody therapies have similar response rates (∼50–80%) in heavily pretreated patients. Similarly, to CAR-T cell therapy, cytokine release syndrome and immune effector cell associated neurotoxicity syndrome are adverse events of key interest and incidence range from ∼40 to 90% and 3 to 20%, respectively. In this review, we highlight the various bispecific immunotherapies under development in the treatment of multiple myeloma with a focus on the data from clinical phase I and II studies.

Keywords:

• Multiple myeloma
• bispecific antibodies
• BiTE therapies
• immunotherapy
• CAR-T

Acknowledgements

Drs. Kazandjian and Landgren thank Sylvester Comprehensive Cancer Center Core Grant (P30 CA240139) for support of this work. Dr. Landgren thanks Paula and Rodger Riney Foundation for its generous support of his research program.

Disclosure statement

DK declares receiving advisory board or consulting fees from Bristol Myers Squibb, Sanofi, and Arcellx. AK declares no competing interests. OL has received grant support from: NCI/NIH, FDA, LLS, Rising Tide Foundation, Memorial Sloan Kettering Cancer Center, MMRF, IMF, Paula and Rodger Riney Foundation, Perelman Family Foundation, Amgen, Celgene, Janssen, Takeda, Glenmark, Seattle Genetics, Karyopharm; has received honoraria for scientific talks/participated in advisory boards for: Adaptive, Amgen, Binding Site, BMS, Celgene, Cellectis, Glenmark, Janssen, Juno, Pfizer; and served on Independent Data Monitoring Committees (IDMC) for international randomized trials by: Takeda, Merck, Janssen, Theradex.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.