FDA Grants National Priority Voucher to Teclistamab/Daratumumab in RRMM

The decision is based on results from the phase 3 MajesTEC-3 trial, which showed a PFS benefit with the teclistamab combination in patients with pretreated multiple myeloma.

The FDA has awarded a national priority voucher to the treatment combination of teclistamab-cqyv (Tecvayli) plus daratumumab (Darzalex) in patients with relapsed/refractory multiple myeloma, according to a press release from the FDA.1

Notably, 16 products have been granted an award under the Commissioner’s National Priority Voucher (CNPV) pilot program. The CNPV program was established to accelerate the review of products that may address 1 or more of several key national priorities. Those priorities are as follows: addressing a US health crisis, delivering 1 or more innovative cures for the American people, addressing a large unmet medical need, promoting domestic drug development and manufacturing to advance the health interests of Americans and strengthen US supply chain resiliency, and increasing affordability. Those who are awarded vouchers receive improved communications with review staff throughout the development process; review decisions are targeted within 1 to 2 months of submission of an application.

This decision came in the wake of recently shared results from the phase 3 MajesTEC-3 trial (NCT05083169) at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition; these data were also published in the New England Journal of Medicine.2,3 MajesTEC-3 evaluated the efficacy of teclistamab plus daratumumab vs subcutaneous daratumumab with pomalidomide (Pomalyst) and dexamethasone (DPd) or bortezomib (Velcade) and dexamethasone (DVd) in patients with relapsed/refractory multiple myeloma.

FDA Commissioner Marty Makary, MD, MPH, stated, “We’re on a mission to deliver more cures and meaningful treatments to the American people. This means proactively identifying potentially transformative therapies. Within hours of the trial results being published in the ASH conference program, FDA leaders read the study, consulted with internal experts, and the following day contacted the company to discuss a national priority voucher. When a treatment demonstrates outstanding trial results, we have a duty to patients to move swiftly.”1

How Effective Was Teclistamab Plus Daratumumab in MajesTEC-3?

With a median follow-up of 34.5 months, the median progression-free survival (PFS) with teclistamab plus daratumumab was not reached compared with 18.1 months with DPd/DVd (HR, 0.17; 95% CI, 0.12-0.23; P <.0001). The 16-month PFS rates were 83.4% vs 29.7%, respectively. Across all subgroups, the PFS benefit with teclistamab plus daratumumab was consistent, including in patients 75 years or older (HR, 0.35) and those with baseline International Staging System (ISS) stage III disease (HR, 0.31).

The overall response rate (ORR) was 89.0% with the experimental regimen vs 75.3% with DPd/DVd (OR, 2.65; 95% CI, 1.68-4.18; P <.0001); the complete response (CR) or better rate was 81.8% vs 32.1%, respectively (OR, 9.56; 95% CI, 6.47-14.14; P <.0001). The median duration of response (DOR) was not estimable (NE; 95% CI, NE-NE) with teclistamab plus daratumumab vs 23.5 months (95% CI, 19.8-29.9) with DPd/DVd; the 36-month DOR rates were 88.5% (95% CI, 83.7%-92.0%) vs 36.4% (95% CI, 28.9%-43.9%), respectively.

Minimal residual disease (MRD) negativity at 10–5, as assessed in the bone marrow by next-generation sequencing per International Myeloma Working Group (IMWG) guidelines, was achieved in 58.4% of the teclistamab group and 17.1% of the DPd/DVd group (OR, 6.78; P <.0001). Among evaluable patients who achieved a CR or better, the MRD negativity rate was 89.3% vs 63.0%, respectively.

With a median follow-up of 34.5 months, the median overall survival (OS) was not reached with the teclistamab combination vs not reached with DPd/DVd (HR, 0.46; 95% CI, 0.32-0.65; P <.0001). The 36-month OS rate was 83.3% vs 65.0%, respectively. Across prespecified subgroups, OS was improved with teclistamab plus daratumumab.

Who Did Teclistamab Plus Daratumumab Benefit in MajesTEC-3?

Patients with relapsed/refractory multiple myeloma who received 1 to 3 prior lines of therapy, including a proteasome inhibitor and lenalidomide, were enrolled in the trial; those with only 1 prior line of treatment were required to be lenalidomide refractory per IMWG criteria. An ECOG performance status from 0 to 2 was required. Those who had prior BCMA-directed therapy and were refractory to anti-CD38 monoclonal antibodies were ineligible for enrollment on the trial.

Dosing was as follows: step-up teclistamab dosing of 0.06 mg/kg and 0.3 mg/kg on days 2 and 4, respectively, then 1.5 mg/kg on days 8, 15 and 22, of cycle 1, with daratumumab given at 1800 mg on days 1, 8, 15, and 22; on cycle 2, patients received both teclistamab at 1.5 mg/kg and daratumumab at 1800 mg on days 1, 8, 15, and 22; on cycles 3 to 6, patients received 3 mg/kg of teclistamab and 1800 mg of daratumumab on days 1 and 15 every 2 weeks; and on cycles 7 and beyond, patients received 3 mg/kg of teclistamab and 1800 mg of daratumumab on day 1 every 4 weeks.

The primary end point was PFS per the independent review committee. Secondary end points included the CR or better rate and ORR, MRD negativity, OS, MySIm total symptom score, and safety.

Was Teclistamab Plus Daratumumab Safe in MajesTEC-3?

Any-grade treatment-emergent adverse events (TEAEs) occurred in 100% of both groups, with grade 3 or 4 events occurring in 95.1% of the teclistamab group and 96.6% of the DPd/DVd group. In both treatment groups, neutropenia was the most common TEAE (78.4% vs 82.8%, respectively). TEAEs led to discontinuation and death in 4.6% and 7.7% of the teclistamab group and 5.5% and 5.9% of the DPd/DVd group.

Notably, cytokine release syndrome (CRS) occurred in 60.1% of the teclistamab group, though no CRS events were grade 3 or higher; 44.2% were grade 1, and 15.9% were grade 2. All CRS events were resolved, and patients were not given prophylactic tocilizumab per study protocol. Immune-effector cell-associated neurotoxicity syndrome occurred in 1.1% of patients, and all events were resolved.

Infections with teclistamab plus daratumumab required diligent use of established immunoglobulin replacement therapy and prophylaxis protocols. The most common treatment-emergent infections or infestations were COVID-19 and urinary tract infection.

Additionally, the time to worsening of multiple myeloma symptoms was significantly longer with teclistamab plus daratumumab vs DPd/DVd, as assessed by the MySIm-Q total symptom score (HR, 0.50; 95% CI, 0.34-0.72; P = .0002).

References

1. FDA proactively awards national priority voucher based on strong phase 3 study results. News release. FDA. December 15, 2025. Accessed December 15, 2025. https://tinyurl.com/2x9uvufa
2. Mateos M-V, Bahlis N, Perrot A, et al. Phase 3 randomized study of teclistamab plus daratumumab versus investigator’s choice of daratumumab and dexamethasone with either pomalidomide or Bortezomib (DPd/DVd) in patients (Pts) with relapsed refractory multiple myeloma (RRMM): Results of majestec-3. Blood. 2025;146(suppl 2): LBA-6. doi:10.1182/blood-2025-LBA-6
3. Costa LJ, Bahlis NJ, Perrot A, et al. Teclistamab plus daratumumab in relapsed or refractory multiple myeloma. N Engl J Med. Published online December 9, 2025. doi:10.1056/NEJMoa2514663