FDA Broadens Options for Relapsed/Refractory Multiple Myeloma With Teclistamab

Treatment options for relapsed/refractory multiple myeloma continue to expand with FDA's accelerated approval of teclistamab (Tecvayli).

The approval stipulates use of the bispecific antibody in adults who have received at least four prior therapies, including an immunomodulator, a proteasome inhibitor, and an anti-CD38 antibody (triple-class refractory disease). The first approved drug of its kind, teclistamab redirects T cells through B-cell maturation antigen (BCMA) and CD3 to activate the immune system against cancer.

The conditional approval is based on results of the multicohort, open-label, multicenter MajesTEC-1 clinical trial program. The efficacy analysis included 110 patients who had received at least three lines of therapy for myeloma but no prior exposure to a BCMA-targeted treatment.

Treatment with teclistamab led to an objective response rate (ORR) of 61.8%. More than 90% of responding patients had ongoing responses at 6 months, and two-thirds had ongoing responses at 9 months.

Recently published updated results from the trial showed an ORR of 63% and median response duration of 18.4 months.

"These are remarkable results," said principal investigator Saad Usmani, MD, of Memorial Sloan Kettering Cancer Center in New York City, in a statement. "We have made great strides treating this disease in the past two decades, and this approval is another important step forward for improving multiple myeloma prognosis. It has many of us in the field very excited."

Among patients treated at the recommended dose of teclistamab, cytokine release syndrome (CRS) occurred in 72% of patients, neurologic toxicity in 57%, and immune effector cell-associated neurologic syndrome in 6%. Grade 3 CRS occurred in 0.6% of patients and grade 3/4 neurologic toxicity in 2.4%. Because of the risk of CRS and neurotoxicity, teclistamab will be available only through an FDA-required risk evaluation and mitigation strategy.

Common adverse events (≥20% of 165 patients in the safety analysis) consisted of pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common (≥20%) grade 3/4 laboratory abnormalities were decreased lymphocytes, neutrophils, white blood cells, hemoglobin, and platelets.

Under the accelerated approval pathway, sponsor Janssen Pharmaceuticals/Johnson & Johnson is required to conduct additional studies to confirm/corroborate the initial results.

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