Teclistamab Approved for Relapsed or Refractory Multiple Myeloma
Expert Perspectives
By Lyn Brook
Published
The FDA has granted approval to teclistamab (Tecvayli®, Janssen Biotech) in combination with daratumumab and hyaluronidase‑fihj for adults with relapsed or refractory multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent.
In addition, the FDA converted the prior accelerated approval of teclistamab monotherapy to traditional approval for adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti‑CD38 monoclonal antibody.
This application was reviewed under the FDA Commissioner’s National Priority Review Voucher (CNPV) pilot program, which is intended to speed evaluation of therapies with potential to address key national priorities.
Why This Approval Matters
Relapsed or refractory multiple myeloma remains difficult to control, particularly after exposure to standard drug classes. Teclistamab is a BCMA×CD3 bispecific T‑cell engager that redirects T cells to kill BCMA‑expressing myeloma cells. The approval of teclistamab combined with daratumumab and hyaluronidase‑fihj moves bispecific therapy earlier in the treatment sequence—after at least one prior line including a proteasome inhibitor and an immunomodulatory agent—and provides a regimen that substantially improves progression-free survival (PFS) compared with established daratumumab-based triplets. In parallel, the conversion of teclistamab monotherapy from accelerated to traditional approval confirms benefit in heavily pretreated patients and solidifies its role after multiple prior lines, including anti‑CD38 therapy.
Breaking Down MajesTEC‑3
Efficacy was studied in MajesTEC‑3 (NCT05083169), a phase 3, open‑label, multicenter trial in 587 patients with relapsed or refractory multiple myeloma. Patients were randomized to receive either:
Teclistamab plus daratumumab and hyaluronidase‑fihj (n=291)
Investigator’s choice (n=296) of either:
Daratumumab and hyaluronidase‑fihj plus pomalidomide plus dexamethasone (DPd)
Daratumumab and hyaluronidase‑fihj plus bortezomib plus dexamethasone (DVd)
The primary efficacy end point was PFS, assessed by independent review committee assessment using International Myeloma Working Group (IMWG) 2016 criteria. Overall survival (OS) was an additional efficacy end point.
Outcomes:
Median PFS was not reached with teclistamab plus daratumumab and hyaluronidase‑fihj versus 18.1 months with control therapy
Median OS was not reached in the teclistamab combination arm and not reached in the control arm
Managing Adverse Events
The teclistamab prescribing information includes a Boxed Warning for life‑threatening or fatal cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell‑associated neurotoxicity syndrome (ICANS). Teclistamab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), the Tecvayli®‑Talvey® REMS.
Beyond CRS, commonly reported adverse reactions with teclistamab in combination with daratumumab and 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.
Dosing and Administration
Refer to the prescribing information for detailed dosing schedules for teclistamab in combination with daratumumab and hyaluronidase‑fihj, including step‑up dosing and monitoring requirements intended to mitigate CRS and neurologic toxicity risk, and for guidance on dose modifications, premedications, and REMS program requirements.
Resources
Clinicaltrials.gov (2026). A study of teclistamab in combination with daratumumab subcutaneously (SC) (Tec-Dara) versus daratumumab SC, pomalidomide, and dexamethasone (DPd) or daratumumab SC, bortezomib, and dexamethasone (DVd) in participants with relapsed or refractory multiple myeloma (MajesTEC-3). NLM identifier: NCT05083169.