FDA Alert

FDA Approves Teclistamab Plus Daratumumab Hyaluronidase-fihj for Adults with Relapsed or Refractory Multiple Myeloma

Kate Young

Key Highlights

  • The FDA approved teclistamab (Tecvayli) plus daratumumab hyaluronidase-fihj for adults with relapsed or refractory multiple myeloma who have received at least 1 prior line of therapy including a proteasome inhibitor and an immunomodulatory agent.
  • The FDA also converted a prior accelerated approval for teclistamab to a traditional approval as a monotherapy in adult patients who have received at least 4 prior lines of therapy.
  • The drug includes a boxed warning for life-threatening or fatal cytokine release syndrome and neurologic toxicity, including immune effector cell-associated neurotoxicity.

The FDA approved teclistamab (Tecvayli) plus daratumumab hyaluronidase-fihj for adults with relapsed or refractory multiple myeloma who have received at least 1 prior line of therapy including a proteasome inhibitor and an immunomodulatory agent following recent safety and efficacy data from the MajesTEC-3 trial. This approval also converted the 2022 accelerated approval for teclistamab to a traditional approval as a monotherapy in adult patients who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.1

A total of 587 participants were randomized in the open-label, multicenter trial to either a teclistamab and daratumumab hyaluronidase-fihj group (n = 291) or to the investigator’s choice of control group of either daratumumab hyaluronidase-fihj, pomalidomide, and dexamethasone or daratumumab hyaluronidase-fihj, bortezomib, and dexamethasone (n = 296).1,2

The primary endpoint was progression-free survival (PFS) assessed by independent review using International Myeloma Working Group 2016 criteria, with overall survival (OS) evaluated as a key secondary endpoint. Median PFS was not reached (NR) in the teclistamab combination arm vs 18.1 months in the control arm (hazard ratio [HR], 0.17; 95% CI, 0.12-0.23; P < .0001). Median OS was NR in both arms at the time of analysis (HR, 0.46; 95% CI, 0.32-0.65; P < .0001).1

In the New England Journal of Medicine report,2 at 36 months, the estimated progression-free survival was 83.4% in the study group with teclistamab plus daratumumab and hyaluronidase-fihj and 29.7% in the control therapy group (P < .001). Of the participants in the study group, 81.8% achieved a complete response or better, 89% achieved an overall response, and 58.4% had minimal residual disease negativity compared with 32.1%, 75.3%, and 17.1% in the control group, respectively (P < .001).2

Serious adverse events were reported in 70.7% of the teclistamab combination group versus 62.4% in the control group, and death resulting from adverse events occurred in 7.1% of the study group versus 5.9% of the control group.2

The most common side effects reported for teclistamab and 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, and the drug includes a boxed warning for life-threatening or fatal cytokine release syndrome and neurologic toxicity, including immune effector cell-associated neurotoxicity.1 The FDA advises clinicians to review  the prescribing information for recommended doses.1

Teclistamab is available only through the Tecvayli-Talvey Risk Evaluation and Mitigation Strategy.

Reference

  1. 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
  2. Costa LJ, Bahlis NJ, Perrot A, et al. Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2026;394(8):739-752. doi:10.1056/NEJMoa2514663