FDA Approves Teclistamab Combination for R/R Multiple Myeloma in Latest CNPV Review

The FDA has approved teclistamab (Tecvayli) daratumumab and hyaluronidase-fihj (Darzalex Faspro) for the treatment of patients with relapsed or refractory multiple myeloma following at least 1 line of prior therapy including a proteasome inhibitor and an immunomodulatory agent.¹

With this approval, the accelerated approval of teclistamab monotherapy in adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody has been converted to standard approval as well.

The efficacy of this new combination was demonstrated in the randomized, open-label, multi-center MajesTEC-3 trial (NCT05083169), a study involving 587 patients. Participants were randomized to receive either the teclistamab and daratumumab hyaluronidase-fihj combination or an investigator’s choice control group, which consisted of either daratumumab hyaluronidase-fihj, pomalidomide, and dexamethasone (DPd) or daratumumab hyaluronidase-fihj, bortezomib, and dexamethasone (DVd).

The primary efficacy outcome was progression-free survival (PFS) as assessed by an independent review committee. Results showed that the median PFS was not reached (95% CI, NE-NE) in the combination arm, compared to 18.1 months (95% CI, 14.6-22.8) in the control group (HR, 0.17; 95% CI, 0.12-0.23; P <0.0001).

Additionally, the median overall survival (OS) was not reached in the teclistamab and daratumumab arm (95% CI, NE-NE) or the control arm (95% CI, 41.4-NE), but a 56% reduction in the risk of death was observed in the experimental arm while (HR, 0.46; 95% CI, 0.32-0.65; P <0.0001).

Safety Concerns

For oncology nurses and advanced practice providers (APPs), safety monitoring remains a critical priority. The prescribing information for teclistamab includes a warnings for life-threatening or fatal cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS).

Due to these significant risks, the drug is only available through the restricted Tecvayli-Talvey Risk Evaluation and Mitigation Strategy (REMS) program. Beyond these boxed warnings, the most common adverse effects observed in the combination study included hypogammaglobulinemia, upper respiratory tract infections, cough, diarrhea, musculoskeletal pain, and COVID-19. Other reported effects included pneumonia, injection site reactions, fatigue, pyrexia, headache, nausea, gastroenteritis, and decreased weight.

The Role of the CNPV Pilot Program

This application was processed under the Commissioner’s National Priority Review Voucher (CNPV) pilot program. Announced in June 2025, this program is designed to dramatically reduce review times for products that align with critical U.S. national health priorities. To qualify for the CNPV, a therapy must meet at least 1 of 5 criteria: addressing a public health crisis, serving as an innovative breakthrough therapy, meeting a large unmet medical need, supporting onshoring and supply chain resilience, or improving affordability.

The CNPV pilot utilizes an ultra-fast timeline, targeting a 1- to 2-month turnaround compared to the 6 or more months required for other priority review programs. The review process itself employs a “tumor board-style” discussion where the initial review team shares its scientific analysis with a multidisciplinary panel known as the CNPV Review Council for collaborative discussion. Despite the accelerated speed, the sources state that the program maintains the FDA’s established standards for safety, effectiveness, and scientific rigor.

The application also utilized the Real-Time Oncology Review (RTOR) pilot program, which allows for the streamlined submission of data prior to the filing of the complete clinical application. Additionally, the applicant submitted a voluntary Assessment Aid to facilitate the agency’s internal assessment. Along with its CNPV status, teclistamab received priority review, breakthrough therapy designation, and orphan drug designation.

Healthcare professionals are encouraged to report any suspected serious adverse events to the FDA’s MedWatch Reporting System. For questions regarding single-patient INDs for investigational products, providers may contact the Oncology Center of Excellence’s Project Facilitate.

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. Commissioner's National Priority Voucher (CNPV) Pilot Program. FDA. Updated February 9, 2206. Accessed March 5, 2026. https://www.fda.gov/industry/commissioners-national-priority-voucher-cnpv-pilot-program