The US FDA has approved Tecvayli (teclistamab-cqyv) in combination with Darzalex Faspro (daratumumab and hyaluronidase-fihj) for the treatment of 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. Johnson & Johnson, which markets both products, said the approval represents the first use of a bispecific T-cell engager antibody in combination with an anti-CD38 antibody as early as the second-line setting in multiple myeloma. Teclistamab, a BCMA-directed CD3 T-cell engager, was originally granted accelerated approval in October 2022 as monotherapy for patients who had received at least four prior lines of therapy. The new approval converts and expands that indication based on Phase 3 data.
The US FDA granted the supplemental Biologics License Application Breakthrough Therapy Designation and Real-Time Oncology Review. The agency also selected the application for participation in the Commissioner's National Priority Voucher Pilot Program, the company said. Tecvayli carries a boxed warning for cytokine release syndrome and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome, and remains available only through a restricted program under a Risk Evaluation and Mitigation Strategy. The combination regimen is administered subcutaneously using a step-up dosing schedule designed to reduce the risk of cytokine release syndrome.
The approval is based on MajesTEC-3, an ongoing Phase 3 randomized trial comparing teclistamab plus daratumumab against investigator's choice of daratumumab with dexamethasone and either pomalidomide or bortezomib. At a median follow-up of three years, the combination demonstrated an 83% reduction in the risk of disease progression or death compared to control regimens (hazard ratio 0.17; 95% CI 0.12–0.23; P<0.0001), with a three-year progression-free survival rate of 83% versus 30% in the control arm. Overall survival also favored the combination (HR 0.46; 95% CI 0.32–0.65; P<0.0001), with 83.3% of patients alive at three years compared to 65.0% in the control arm. Response rates were higher across all secondary endpoints: overall response rate was 89.0% versus 75.3%, complete response or better was 81.8% versus 32.1%, and minimal residual disease negativity was 58.4% versus 17.1%. The results were presented in December 2025 at the American Society of Hematology Annual Meeting and published simultaneously in The New England Journal of Medicine. Rates of Grade 3/4 treatment-emergent adverse events were similar between arms (95.1% versus 96.6%). Cytokine release syndrome occurred in 60.1% of patients in the combination arm, though all cases were Grade 1 or 2. Grade 3 or higher infections were observed in 54.1% of patients receiving the combination, declining after the first six months of treatment.
The approval arrives in a relapsed or refractory multiple myeloma treatment landscape that has expanded considerably in recent years. BCMA-directed CAR-T cell therapies, including ciltacabtagene autoleucel and idecabtagene vicleucel, received expanded approvals in 2024 for earlier lines of relapsed disease. Belantamab mafodotin, a BCMA-directed antibody-drug conjugate, was re-approved in combination regimens following its earlier voluntary withdrawal. Several competing bispecific antibodies targeting BCMA or alternative antigens such as GPRC5D and FcRH5 are in Phase 3 development from companies including Pfizer, AbbVie, Regeneron, and Roche. The MajesTEC-3 data represent the first randomized Phase 3 results for a bispecific antibody in this setting, and the magnitude of the progression-free survival separation from standard-of-care comparators sets a benchmark against which these competing programs will be measured. For patients with multiple myeloma, approximately 40% of whom experience disease relapse according to the company, the approval adds a subcutaneous, off-the-shelf regimen accessible across practice settings without the manufacturing logistics required for cell therapy.
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