The FDA approved teclistamab (Tecvayli) in combination with daratumumab hyaluronidase-fihj (Darzalex Faspro) on March 5, 2026, for adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent. The approval, the third issued under the FDA Commissioner’s National Priority Review Voucher (CNPV) pilot program, came just 55 days after filing, a review speed that underscores both the agency’s posture under Commissioner Marty Makary and the strength of the underlying clinical data.
The decision simultaneously converts teclistamab’s 2022 accelerated approval as a monotherapy, for patients with at least four prior lines including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody, to a traditional approval, formally closing the loop on one of the most closely watched bispecific antibody launches in hematologic oncology.
MajesTEC-3: A Trial Dataset That Rarely Appears in Hematologic Oncology
The approval rests on MajesTEC-3 (NCT05083169), a randomized, open-label, multicenter Phase 3 trial enrolling 587 patients who had received one to three prior lines of therapy. Patients were randomized 1:1 to teclistamab plus daratumumab (n=291) versus investigator’s choice of daratumumab, pomalidomide, and dexamethasone (DPd) or daratumumab, bortezomib, and dexamethasone (DVd) (n=296), with 91% of control arm patients receiving DPd. Patients were required to be refractory to lenalidomide if they had received only one prior line.
At a median follow-up of 34.5 months, the data are exceptional across every primary and secondary endpoint:
| Endpoint | Tec-Dara | DPd/DVd | Hazard Ratio / P-value |
|---|---|---|---|
| Median PFS | Not reached | 18.1 months | HR 0.17 (95% CI: 0.12–0.23); p<0.0001 |
| 36-month PFS rate | 83.4% | 29.7% | — |
| ORR | 89.0% | 75.3% | OR 2.65; p<0.0001 |
| CR or better | 81.8% | 32.1% | OR 9.56; p<0.0001 |
| MRD negativity (10⁻⁵) | 58.4% | 17.1% | OR 6.78; p<0.0001 |
| Median OS | Not reached | Not reached | HR 0.46 (95% CI: 0.32–0.65); p<0.0001 |
| 36-month OS rate | 83.3% | 65.0% | — |
An 83% reduction in the risk of disease progression or death, combined with a 54% reduction in the risk of death, against a daratumumab-based triplet control arm is a result that has rarely been achieved in the second-line myeloma setting in modern trials. The depth of response is equally striking: an 81.8% complete response rate and 58.4% MRD negativity in the combination arm represent a threshold of disease eradication that most salvage regimens do not approach.
Read more on about the MajesTEC-3 Trial on OncoDaily.
Mechanism of Action: Dual Immune Engagement
Teclistamab is a BCMA × CD3 bispecific T-cell engager. It simultaneously binds BCMA (B-cell maturation antigen), a surface protein highly expressed on myeloma plasma cells, and CD3 on T-cells, physically bridging tumor cell and immune effector to drive T-cell-mediated cytotoxicity against BCMA-expressing myeloma cells. The combination with daratumumab (an anti-CD38 antibody) adds a complementary layer of immune killing via antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity, and NK-cell activation against CD38-positive myeloma cells.
The mechanistic rationale for combining BCMA-directed T-cell engagement with CD38-directed antibody killing is the potential for non-overlapping target engagement and synergistic immune activation, two mechanisms disrupting myeloma cell survival simultaneously, via independent pathways. MajesTEC-3 confirms that this synergy translates clinically: ORR of 89% and CR rate of 81.8% against a control arm already receiving an active triplet goes well beyond additive effect.
Regulatory Architecture: A Milestone for the CNPV Program
The CNPV (Commissioner’s National Priority Voucher) program is new, and this approval marks only its third decision since the program’s inception. The program functions by proactively awarding a voucher to sponsors of drugs with high-impact Phase 3 data, enabling accelerated FDA collaboration, rolling review, and a condensed approval timeline. The FDA proactively awarded the Tec-Dara voucher on December 15, 2025, after agency leadership reviewed the MajesTEC-3 dataset, an unusual move that signals how much institutional weight the data carried before formal filing.
The 55-day review is fast by any benchmark. By comparison, standard Priority Review targets 6 months. This speed, while partly attributable to the CNPV mechanism, also reflects the review efficiency enabled by the Real-Time Oncology Review (RTOR) program, which allows data to be submitted and reviewed on a rolling basis prior to formal NDA filing, and Project Orbis, the FDA’s framework for simultaneous international review in collaboration with Health Canada and Switzerland’s Swissmedic.
FDA Commissioner Marty Makary, M.D., M.P.H., spoke to the agency’s intent:
Multiple myeloma is notoriously challenging to treat. When we saw the most impressive second-line myeloma trial results in history, we acted quickly to bring this finding to everyday Americans wrestling with the disease.
Dr. Tracy Beth Høeg, M.D., Ph.D., Acting Director of the FDA’s Center for Drug Evaluation and Research, added:
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/Bloomberg/Getty Images
Competitive Landscape: Reshaping Second-Line Myeloma
The approval enters a second-line myeloma space that has been predominantly defined by triplet regimens, DPd, DVd, carfilzomib-based combinations, following lenalidomide. The bispecific antibody class is already reshaping later lines: teclistamab’s monotherapy approval (2022), elranatamab (Elrexfio, Pfizer), and talquetamab (Talvey, J&J) have demonstrated activity in heavily pre-treated patients. Moving a bispecific-based combination into second-line represents a substantial escalation of this class’s role in the treatment algorithm.
For Johnson & Johnson’s hematology franchise, Tec-Dara reinforces a strategy of leveraging Darzalex’s established global commercial infrastructure, currently generating multi-billion-dollar annual revenues, as a backbone onto which novel immune-engaging agents can be layered. The Tecvayli-Darzalex combination is the most advanced instantiation of that strategy to date.
Forward-Looking Analysis
The 36-month OS rate of 83.3% in MajesTEC-3’s combination arm, against 65% in the control, is a difference of 18 percentage points at three years in a disease historically associated with median survival of two to three years in the relapsed setting. As median OS matures in both arms, the absolute survival benefit will sharpen, and those data will be central to community adoption and payer negotiation.
The broader implication: if bispecific antibody combinations can deliver durable deep responses with MRD negativity rates approaching 60% in second-line myeloma, the field will increasingly focus on whether treatment-free intervals and functional cures are achievable, a question that MajesTEC-3’s long-term follow-up data will be critical to answering.
Read more biotech insights on OncoDaily Biotech.
Written by: Semiramida Nina Markosyan, Editor, OncoDaily Canada