FDA Approves Teclistamab Plus Daratumumab Hyaluronidase for Relapsed or Refractory Multiple Myeloma

Key Clinical Summary:

• On March 5, 2026, the US FDA approved teclistamab plus daratumumab hyaluronidase for adult patients with relapsed or refractory multiple myeloma who received ≥1 prior line of therapy based on the phase 3 MajesTEC-3 trial, which randomized 587 patients to teclistamab plus daratumumab versus DPd or DVd.
• Median PFS was not reached with the combination versus 18.1 months with control. Overall survival also favored teclistamab. 
• The FDA also converted prior accelerated approval of teclistamab monotherapy (≥4 prior lines) to traditional approval.

On March 5, 2026, the US Food and Drug Administration (FDA) approved teclistamab plus daratumumab hyaluronidase for adult patients with relapsed or refractory multiple myeloma who have received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent. This approval was based on results from the MajesTEC-3 trial.

In this multicenter, open-label trial, 587 patients were randomized to receive either teclistamab plus daratumumab hyaluronidase (n = 291) or investigator’s choice control therapy with daratumumab hyaluronidase, pomalidomide, and dexamethasone or daratumumab hyaluronidase, bortezomib, and dexamethasone (n = 296). Primary end points included progression-free survival (PFS), as assessed via independent review according to International Myeloma Working Group (IMWG) 2016 criteria, and overall survival (OS). A key secondary end point was safety. 

At analysis, median PFS was not reached in the teclistamab plus daratumumab hyaluronidase arm and 18.1 months in the control arm (hazard ratio [HR], 0.17; 95% confidence interval [CI], 0.12 to 0.23; P < 0.0001). Median OS was not reached in either treatment arm (HR, 0.46; 95% CI, 0.32 to 0.65; P < 0.0001). 

The most common adverse events observed with teclistamab plus daratumumab hyaluronidase included hypogammaglobulinemia, upper respiratory tract infection, cough, diarrhea, musculoskeletal pain, COVID-19, pneumonia, injection site reactions, fatigue, pyrexia, headache, nausea, gastroenteritis, and decreased weight.

The prescribing information includes a Boxed Warning for life-threatening or fatal cytokine release syndrome and neurologic toxicities, including immune effector cell-associated neurotoxicity syndrome (ICANS). 

Based on this data, the FDA has additionally converted the prior accelerated approval of teclistamab as monotherapy to traditional approval for adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. 

Teclistamab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the Tecvayli-Talvey REMS.

Source:

US Food and Drug Administration. FDA approves teclistamab in combination with daratumumab hyaluronidase-fihj for relapsed or refractory multiple myeloma. Accessed March 5, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-teclistamab-combination-daratumumab-hyaluronidase-fihj-relapsed-or-refractory-multiple