C. Brooke Adams, Pharm.D., BCOP

Bispecific antibodies are a major advance in multiple myeloma treatment with outstanding efficacy, with many clinical trials underway that are providing the evidence for using them in earlier lines of treatments.

Health systems and clinics need to work together to manage care of the potentially dangerous side effects of bispecific antibodies during the early, step-up phase of treatment, Adams said. Those side effects include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome.

Adams said she has seen firsthand the difference that bispecific antibodies have made. “Patients that would have never gotten into remission are getting into remission. Patients that would have never seen the birth of their grandchild are now seeing the birth of their grandchild,” Adams said. Some real-world data are showing slightly reduced efficacy that was seen in clinical trials, Adams said. There is a need for research that would develop comparator data to other therapies, she noted.

LINKER-MM4 is an open-label study of linvoseltamab as monotherapy in patients who have been newly diagnosed with multiple myeloma. Adams said the results are showing “outstanding efficacy” of 95% that may be due to patients having healthier T cells while still in early-stage treatment.

Bispecific antibodies could mean simpler regimens that will require fewer clinic visits, Adams said. She also mentioned the possibility of fixed-duration therapy and patients getting to the status of minimal residual disease negative faster.

After step-up dosing, treatment with bispecific antibodies does not require the use of steroids, Adams noted, so patients are spared steroid side effects. Bispecific antibody treatment advances could also mean avoiding proteasome inhibitors, which cause neuropathy, she said.

Bispecific antibodies, like other treatments initially approved for later lines of therapy, are moving "upstream" in multiple myeloma treatment, Adams said. She discussed the MajesTEC-3 trial that led to the approval of teclistamab plus daratumumab as second-line therapy, the IMMUNOPLANT trial of linvoseltamab, and the MajesTEC-7 trial comparing a combination of teclistamab, daratumumab and lenalidomide with a combination of talquetamab, daratumumab and lenalidomide.

National Comprehensive Cancer Network (NCCN) guidelines have limited influence on multiple myeloma treatment and its sequencing because treatment is evolving so quickly, Adams said. “Therapies are coming out left and right faster than we can keep up with, and it’s faster than the NCCN can keep up with as well,” she said.

Teclistamab has a clear advantage because it was the first bispecific antibody to be approved, said Adams. Route of administration, the pace of the step-up dosing, the relationship with community providers and risk evaluation and mitigation strategies (REMS) requirements all factor into formulary decisions, she said. Payers may start preferring one bispecific antibody over another because the efficacy among them is similar, Adams said.

Bispecific antibodies are currently approved as late-line therapy, but they are moving up to earlier lines “as they prove their worth, so to speak,” said Adams. She discussed the efficacy, route of administration, dosing mechanism of action, and the various tradeoffs among the four bispecific antibodies that the FDA has approved: teclistamab, elranatamab, talquetamab and linvoseltamab.

Bispecific antibodies are highly efficacious and have a milder side effect profile than other late-line treatments for multiple myeloma, according to Adams.

Multiple myeloma accounts for only 1.8% of cancers, but it is the second-most common blood cancer, with approximately 36,000 new cases diagnosed each year in the U.S., says Adams. The number of treatment choices has proliferated as new innovative therapies, such as the bispecific antibodies and chimeric antigen receptor (CAR) T-cell therapy, have been developed.