Bispecific Antibodies Are Reshaping Multiple Myeloma Care: Prerna Mewawalla, MD

Bispecific antibodies have rapidly transformed the treatment landscape for multiple myeloma (MM), offering new hope to patients whose disease no longer responds to standard therapies. According to Prerna Mewawalla, MD, director of the stem cell transplant program at Allegheny Health Network and associate professor at Drexel University College of Medicine, these therapies work by harnessing the patient’s own immune system in highly targeted ways.

Bispecific antibodies are designed to bind 2 targets simultaneously, she explains. One arm attaches to a marker on the myeloma cell—such as B-cell maturation antigen (BCMA), G protein-coupled receptor class C group 5 member D, or Fc receptor-homolog 5—while the other binds to CD3 on T cells. This dual engagement activates T cells, prompting cytokine release and ultimately killing the cancerous plasma cells. Several BCMA-directed bispecifics, including teclistamab, elranatamab, and linvoseltamab, are already in clinical use, while others target alternative antigens and continue to be studied in trials.

Before bispecific therapies and chimeric antigen receptor (CAR) T-cell treatments were available, outcomes were far more limited for patients who became refractory to immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies. Response rates in later lines of therapy hovered around 30%. Today, bispecific antibodies are achieving response rates as high as 80% in earlier relapse settings, an unprecedented shift driven by advances in immune-based therapies.

Choosing between CAR T-cell therapy and bispecific antibodies depends on several factors. If a patient is fit and eligible for CAR T-cell therapy, Mewawalla typically prioritizes it first.

“I would say if there’s a patient who is eligible for CAR T and is fit enough to get CAR T, I do always prioritize CAR T first,” she says, “because we do know that the efficacy of CAR T, BCMA CAR T, significantly decreases if you use bispecifics first.”

However, CAR T-cell therapy requires manufacturing time, making it less suitable for patients with rapidly progressing disease. Bispecific antibodies, which are “off the shelf,” can be started almost immediately.

Bispecifics also offer advantages for patients with existing neurological issues or those unable or unwilling to travel or stay in the hospital. With lower rates of severe neurotoxicity and greater logistical flexibility, bispecific antibodies have become a vital option, expanding access to effective treatment for a broader range of patients.