FDA

FDA OKs Tecvayli plus Darzalex Faspro for relapsed or refractory multiple myeloma

March 12, 2026

On March 5, 2026, FDA approved Tecvayli (teclistamab-cqyv) in combination with Darzalex Faspro (daratumumab/hyaluronidase-fihj) for adult patients with relapsed or refractory multiple myeloma who've received at least 1 prior line of therapy including a proteasome inhibitor and an immunomodulatory agent. In addition, FDA converted Tecvayli’s accelerated approval (granted in 2022) for monotherapy in adults with relapsed or refractory multiple myeloma who've received at least 4 prior lines of therapy, to traditional approval.

Efficacy

Efficacy was evaluated in MajesTEC-3 (NCT05083169), a randomized, open-label, multi-center trial, in which 587 patients were randomized to the teclistamab-cqyv and daratumumab/hyaluronidase-fihj group (n = 291) or investigator’s choice of either daratumumab/hyaluronidase-fihj, pomalidomide, and dexamethasone [DPd] or daratumumab/hyaluronidase-fihj, bortezomib, and dexamethasone [DVd] (n = 296). The study included patients who'd previously received 1 to 3 prior lines of therapy including a proteasome inhibitor and lenalidomide. Patients who'd received only 1 prior line of therapy must have been refractory to lenalidomide. Patients who had disease refractory to a prior anti-CD38 monoclonal antibody therapy, or who'd received any prior BCMA-directed therapy were excluded.

Median age of study participants was 64 years (range, 25 to 88) with 38% aged 65 to 74 years and 10% aged ≥75 years; 55% were male; 65% were White, 6% were Black or African American, and 22% were Asian. The International Staging System (ISS) at screening was stage I in 63%, stage II in 29%, and stage III in 8%. High-risk cytogenetics (presence of del(17p), t(4;14) or t(14;16)) were present in 35% of patients. Extramedullary disease was present in 5% of patients. The median number of prior lines of therapy was 2 (range, 1 to 3), with 38% who received 1 prior line of therapy.

The primary endpoint was progression-free survival (PFS). Median PFS was not reached (NR) (95% confidence interval [CI]: NE [not estimable], NE) in the teclistamab-cqyv and daratumumab hyaluronidase-fihj arm and was 18.1 months (95% CI, 14.6-22.8) in the control arm. This represents an 83% reduction in the risk of disease progression or death with the teclistamab-cqyv and daratumumab/hyaluronidase-fihj combination (hazard ratio [HR], 0.17; 95% CI, 0.12-0.23; P <0.0001).

Overall survival (OS) was a secondary endpoint. Median OS was NR (95% CI, NE, NE) and NR (95% CI, 41.4, NE) in the respective arms. The teclistamab-cqyv and daratumumab/hyaluronidase-fihj combination was associated with a 54% reduction in the risk of death compared with the control regimen (HR, 0.46; 95% CI, 0.32-0.65; P <0.0001).

Safety

The prescribing information for Tecvayli includes a boxed warning for life threatening or fatal cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS). Tecvayli is available only through a restricted Risk Evaluation and Mitigation Strategy program (Tecvayli-Talvey REMS).

In addition to CRS, the most common adverse reactions (≥20%) in patients who received teclistamab-cqyv in combination with daratumumab/hyaluronidase-fihj were hypogammaglobulinemia, upper respiratory tract infection, cough, diarrhea, musculoskeletal pain, COVID-19, pneumonia, injection site reaction, fatigue, pyrexia, headache, nausea, gastroenteritis, and decreased weight.

Most common Grade 3 to 4 lab abnormalities (≥20%) with teclistamab-cqyv (as monotherapy or in combination with daratumumab/hyaluronidase-fihj) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets.

Sources:

Johnson & Johnson. (2026, March 5). Johnson & Johnson Announces U.S. FDA Approval of TECVAYLI plus DARZALEX FASPRO for Relapsed/Refractory Multiple Myeloma, Offering a Potential New Standard of Care as Early as Second Line. [Press release]. https://www.jnj.com/media-center/press-releases/johnson-johnson-announces-u-s-fda-approval-of-tecvayli-plus-darzalex-faspro-for-relapsed-refractory-multiple-myeloma-offering-a-potential-new-standard-of-care-as-early-as-second-line

FDA. (2026, March 5). FDA approves teclistamab in combination with daratumumab hyaluronidase-fijh for relapsed or refractory multiple myeloma. [Press release]. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-teclistamab-combination-daratumumab-hyaluronidase-fihj-relapsed-or-refractory-multiple

Tecvayli (teclistamab-cqyv) [Package insert]. Janssen Biotech, Inc. https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/TECVAYLI-pi.pdf Revised March 2026.