FDA Approves Teclistamab Combination for Relapsed/Refractory Multiple Myeloma

The Food and Drug Administration (FDA) has approved teclistamab-cqyv in combination with daratumumab hyaluronidase-fihj for adults with relapsed or refractory multiple myeloma who have received at least one prior line of therapy. This approval also expands the use of teclistamab monotherapy to include patients with relapsed or refractory multiple myeloma following at least four prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.

Significant Efficacy Demonstrated in MajesTEC-3 Trial

The FDA’s decision is based on data from the randomized phase 3 MajesTEC-3 trial, which demonstrated a substantial reduction in the risk of disease progression or death compared to standard of care. Specifically, patients receiving the teclistamab-daratumumab combination experienced an 83% reduction in risk for disease progression or death (HR = 0.17; 95% CI, 0.12 – 0.23) and a 46% reduction in the risk of death (HR = 0.46; 95% CI, 0.32-0.65) compared to the control group.

The trial also revealed significant improvements in long-term outcomes, with 3-year progression-free survival (PFS) rates of 83.4% versus 29.7% and 3-year overall survival (OS) rates of 83.3% versus 65% in the teclistamab-daratumumab combination group.

A New Approach to Multiple Myeloma Treatment

“This new treatment option can redefine how we approach [relapsed or refractory multiple myeloma] treatment by giving health care providers a regimen with improvement in PFS and OS and a well-characterized safety profile,” said Luciano J. Costa, MD, professor of multiple myeloma and director of the multiple myeloma research and treatment program at the University of Alabama at Birmingham, in a Johnson & Johnson press release.

Dr. Costa added, “The option to use this regimen as early as second line is particularly key because patients with [multiple myeloma] often experience multiple relapses and reduced responsiveness to therapy over time, which makes earlier treatment with the most effective therapies critical. The steroid-sparing approach may reduce toxicity and improve tolerability.”

Trial Design and Patient Population

The MajesTEC-3 trial involved 587 patients randomly assigned to receive either the teclistamab-daratumumab hyaluronidase-fihj combination (n = 291) or an investigator’s choice regimen of daratumumab hyaluronidase-fihj with pomalidomide and dexamethasone, or daratumumab hyaluronidase-fihj with bortezomib and dexamethasone (n = 296).

Safety Profile

Common side effects associated with teclistamab plus daratumumab hyaluronidase-fihj include hypogammaglobulinemia, upper respiratory tract infection, cough, diarrhea, musculoskeletal pain, COVID-19, pneumonia, injection site reaction, fatigue, pyrexia, headache, nausea, gastroenteritis, and decreased weight. Serious adverse events occurred in 70.7% of patients treated with the combination therapy compared with 62.4% of patients in the control group.

Treatment discontinuations due to adverse events were less frequent in the teclistamab-daratumumab combination group (4.6% vs. 5.5%), but grade 5 treatment-emergent adverse events occurred more frequently (7.1% vs. 5.9%).

Prescribing information for teclistamab includes a boxed warning for life-threatening or fatal cytokine release syndrome and neurologic toxicity, including immune effector cell-associated neurotoxicity.