FDA Approves First Bispecific Antibody, Teclistamab, for R/R Multiple Myeloma

The FDA on Wednesday granted approval to Janssen Biotech’s teclistamab (Tecvayli) for treatment of relapsed or refractory multiple myeloma, marking a new class of therapy now available for patients whose disease had progressed on other types of therapy.

Teclistamab is a bispecific T-cell engager antibody that targets both B-cell maturation antigen (BCMA) expressed on the surface of myeloma cells and the CD3 receptor expressed on the surface of T cells, according to a release from Janssen. It is injected subcutaneously, and its approval is for adults with multiple myeloma who have received at least 4 earlier lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

The accelerated approval was based on the results of MajesTEC-1, a single-arm, multicenter phase 1/2 study (NCT03145181 and NCT04557098) involving 110 patients who had previously received at least 3 lines of therapy (including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody) but who had not yet received BCMA-targeted therapy. The median number of prior lines of therapy was 5, and 78% of patients had received 4 or more prior lines of therapy.

Investigators found an overall response rate of 61.8% (95% CI, 52.1%-70.9%) among these patients receiving teclistamab in the trial, and 28.2% of patients achieved a complete response or better. The effects were seen quickly, with a median time to first response of 1.2 months. These results were first reported at the American Society of Hematology Annual Meeting in December 2021.

The FDA’s approval of teclistamab comes with a boxed warning for cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell–associated neurotoxicity (ICANS). As such, the drug will be available only through a Risk Evaluation and Mitigation Strategy program. In MajesTEC-1, CRS occurred in 72% of patients, neurologic toxicity in 57%, and ICANS in 6%. Clinicians are advised to follow a step-up dosing schedule when initiating treatment with teclistamab to lower the risk of CRS, which can be life-threatening or fatal.

Other common adverse reactions occurring in at least 20% of patients were fever, musculoskeletal pain, injection site reaction, and fatigue. The most frequent grade 3 to 4 laboratory abnormalities were decreases in lymphocytes, neutrophils, white blood cells, hemoglobin, and platelets.

“As a clinician and researcher, I see first-hand the human toll of this incurable disease. The approval of teclistamab, as the first bispecific antibody in relapsed or refractory multiple myeloma, is a meaningful step in helping many of these hard-to-treat patients,” Ajai Chari, MD, professor of medicine at the Icahn School of Medicine at Mount Study and an investigator on the MajesTEC-1 study), said in the company’s press release.