FDA Approves Teclistamab Plus Daratumumab Hyaluronidase-fihj for Relapsed/Refractory Multiple Myeloma

Teclistamab (Tecvayli; Janssen Biotech, Inc) plus daratumumab hyaluronidase-fihj received FDA approval for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent.¹ The decision is supported by data from the MajesTEC-3 (NCT05083169) trial.

In addition to this approval, the FDA changed the accelerated approval of teclistamab as a monotherapy to a traditional approval.

“It is very exciting to see such a rapid FDA approval of this groundbreaking treatment for one of the most common blood cancers,” Tracy Beth Høeg, MD, PhD, acting director of the FDA’s Center for Drug Evaluation and Research, said in an official release.² “[Teclistamab plus daratumumab hyaluronidase-fihj] was found in a randomized trial to reduce the risk of death by over 50% compared with current standard of care in patients with [RRMM]. I am very grateful to the FDA scientists involved in this thorough and efficient review.”

Teclistamab Plus Daratumumab Improved Survival in RRMM

MajesTEC-3 is a randomized, open-label, multicenter trial investigating teclistamab plus daratumumab compared with investigators of either daratumumab hyaluronidase-fihj, pomalidomide (Pomalyst; Bristol Myers Squibb), and dexamethasone (DPd) or daratumumab hyaluronidase-fihj, bortezomib (Velcade; Millennium Pharmaceuticals), and dexamethasone (DVd). The primary end point was progression-free survival (PFS) by independent review committee assessment based on International Myeloma Working Group 2016 criteria. An additional secondary outcome of overall survival (OS) was also evaluated.

A total of 587 patients were randomly assigned to either treatment arm, with 291 receiving teclistamab plus daratumumab hyaluronidase-fihj and 296 receiving the investigator’s choice treatment.

PFS outcomes strongly favored the combination regimen. The median PFS had not yet been reached in patients receiving teclistamab plus daratumumab hyaluronidase-fihj (95% CI, not estimable), whereas patients in the control group experienced a median PFS of 18.1 months (95% CI, 14.6–22.8). This translated to an 83% reduction in the risk of disease progression or death with the investigational combination (HR, 0.17; 95% CI, 0.12-0.23; P < .0001).

OS results also favored the combination therapy. Median OS was not reached in either treatment arm at the time of analysis; however, the CIs differed between groups, remaining not estimable in the teclistamab plus daratumumab arm and extending from 41.4 months to not estimable in the control arm. The combination therapy was associated with a significant 54% reduction in the risk of death compared with the control regimen (HR, 0.46; 95% CI, 0.32-0.65; P < .0001).

Teclistamab Safety

The prescribing information for teclistamab carries a boxed warning highlighting the risk of severe or potentially fatal cytokine release syndrome (CRS) as well as neurologic adverse events, including immune effector cell–associated neurotoxicity syndrome. Due to these safety concerns, the therapy is distributed only through a restricted Risk Evaluation and Mitigation Strategy program.

Beyond CRS, patients receiving teclistamab in combination with daratumumab hyaluronidase‑fihj most frequently experienced adverse effects (AEs) such as hypogammaglobulinemia, upper respiratory tract infections, cough, diarrhea, musculoskeletal pain, COVID-19, pneumonia, injection-site reactions, fatigue, fever, headache, nausea, gastroenteritis, and weight loss.

Pharmacists should take the necessary precautions when administering this treatment to patients through monitoring and prompt response to any AEs.

REFERENCES

1. FDA approves teclistamab in combination with daratumumab hyaluronidase-fihj for relapsed or refractory multiple myeloma. FDA. March 5, 2026. 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. FDA grants third approval under the national priority voucher program. FDA. March 5, 2026. Accessed March 5, 2026. https://www.fda.gov/news-events/press-announcements/fda-grants-third-approval-under-national-priority-voucher-program