BCMA-targeted therapies for multiple myeloma: strategies to maximize efficacy and minimize adverse events

Immunotherapies targeting B cell maturation antigen (BCMA) in multiple myeloma are transitioning through trials and entering the clinic, and will likely become a core pillar in myeloma therapeutics. These agents demonstrate unprecedented activity in multiply relapsed patients, but notwithstanding the short follow-up times their survival curves do not appear to demonstrate a plateau, and the treatments inevitably bring with them a range of toxicities that might be associated with tolerability issues.

We will briefly lay out the current therapeutic landscape in multiple myeloma, before introducing BCMA and explaining its significance. We will address in turn the three key classes of anti-BCMA immunotherapies: antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T cells. We describe the mechanisms of action of these classes and review the evidence supporting their efficacy and toxicities. We then bring all three therapies into one discussion that explores how to mitigate toxicities and overcome myeloma's ability to resist these potent treatments.

Finally, we take the discussion back to the clinic, and consider how we might deploy anti-BCMA therapies most effectively for our patients. We consider the sequencing of treatment, and what further evidence is needed to more fully inform our therapy decisions.