Teclistamab-cqyv (Tecvayli, Janssen Biotech) was granted accelerated approval on Oct. 25, 2022, for the treatment of adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy that included a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Teclistamab-cqyv represents the first approval of a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager.

The recommended treatment regimen for subcutaneous injection includes a 7-day step-up schedule (on days 1, 4, and 7) followed by weekly dosing. Patients should be hospitalized during the initial step-up phase, and pretreatment with a corticosteroid, histamine-1 receptor antagonist, and antipyretic may be required.

Teclistamab carries a Boxed Warning for life-threatening or fatal cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS). CRS was reported in 72% of patients (one grade 3 reaction),  neurologic toxicity in 57%, and ICANS in 6%. Recurrent CRS was observed in 33%. Teclistamab is available only through a Risk Evaluation and Mitigation Strategy (REMS) program.

Among the 165 patients in the safety population, the most common grade 3 to 4 laboratory abnormalities, occurring in ≥20%, were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets. The most common adverse reactions, also ≥20%, were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. Overall, 45% of patients developed grade 3 or 4 infections.

The approval was based on the phase 1-2 MajesTEC-1 trial, a single-arm, open-label study with an efficacy population of 110 patients. The overall response rate (ORR), which was the primary endpoint, was 61.8% (95% CI, 52.1-70.9). The estimated duration of response rate among responders was 90.6% at 6 months and 66.5% at 9 months, with a median follow-up of 7.4 months. A complete response was seen in 28.2%.

References
FDA approves teclistamab-cqyv for relapsed or refractory multiple myeloma. 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-teclistamab-cqyv-relapsed-or-refractory-multiple-myeloma

Tecvayli (teclistamab-cqyv) injection [package insert]. Horsham, PA: Janssen Biotech, Inc; 10/2022.