MajesTEC-9 Data Add to Accolades for Teclistamab in Multiple Myeloma

New topline data on teclistamab-cqyv (Tecvayli; Johnson & Johnson/Janssen) bolster the first-in-class bispecific T-cell engager’s reputation for its ability to greatly improve patient outcomes while living with relapsed/refractory multiple myeloma (MM).

These findings from the phase 3 MajesTEC-9 (NCT05572515) trial come on the heels of results presented at meetings last year showing the B-cell maturation antigen (BCMA) x CD3 bispecific antibody hard at work across various disease settings within MM.2-4 They confirm teclistamab’s superiority at improving progression-free survival (PFS) and overall survival (OS) vs standard-of-care therapy in as early as the second line,1 as well as build on MajesTEC-3 trial (NCT05083169) results showing that when it is administered in combination with daratumumab and hyaluronidase-fihj (Darzalex Faspro; Janssen), teclistamab can significantly improve PFS and OS for patients naive or sensitive to an anti-CD38 therapy.5 Eighty-five percent of patients in MajesTEC-9 alone were refractory to anti-CD38 monoclonal antibodies, 79% were refractory to lenalidomide, and more than 90% were refractory to their immediate prior line of treatment.1

“The MajesTEC-9 results reinforce the potential of Tecvayli to transform treatment earlier in the multiple myeloma journey, with an immunotherapy regimen widely available for all appropriate patients, including those commonly treated in the community setting,” said Roberto Mina, MD, associate professor, Winship Cancer Institute of Emory University, in a statement. “The impressive results show a significant improvement in progression-free and overall survival as a monotherapy in patients with refractory multiple myeloma, and together with the MajesTEC-3 results, help establish Tecvayli as an essential therapy for patients as early as first relapse.”

Ongoing approval of teclistamab for adult patients with relapsed/refractory MM, who have received at least 4 prior lines of therapy, is contingent on demonstrated clinical benefit in confirmatory trials. The drug is currently approved under the FDA’s accelerated approval pathway. | Image Credit: © luchschenF-stock.adobe.com

There was 40% reduced risk of death (HR, 0.60; 95% CI, 0.43-0.83) and a clinically meaningful and statistically significant 71% reduced risk of disease progression or death (HR, 0.29; 95% CI, 0.23-0.38) in patients refractory to anti-CD38 therapy and lenalidomide, according to these latest findings from MajesTEC-9 released on January 14. No new safety concerns were identified, with any adverse effects clinically manageable. However, top safety concerns are cytokine release syndrome, hepatotoxicity, neutropenia, hypersensitivity and other administration reactions, embryo-fetal toxicity, and neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome.

In MajesTEC-9, patients were randomized to receive subcutaneous teclistamab monotherapy or physician’s choice of standard-of-care therapy, either pomalidomide, bortezomib (Velcade), and dexamethasone (PVd) or carfilzomib (Kyprolis) and dexamethasone (Kd), regimens that are a combination of oral and subcutaneous administration (PVd) or oral and intravenous administration (Kd).6 To participate in the trial, patients needed a documented MM diagnosis, have received 1 to 3 prior lines of antimyeloma therapy (including a prior anti-CD38 monoclonal antibody and lenalidomide), have documented progressive disease or failed their immediate prior line of therapy, have an Eastern Cooperative Oncology Group performance status score of 0 to 2, and adhere to all study-related lifestyle restrictions. Female patients must also not be pregnant or breastfeeding while enrolled or plan to become pregnant within 6 months of their final study dose. Exclusion criteria included receiving prior BCMA-directed therapy, a live attenuated vaccine within 4 weeks of randomization, having central nervous system involvement or signs of MM-related meningeal involvement, and a maximum cumulative corticosteroid dose 140 mg or more of prednisone or an equivalent within 14 days of randomization.

Under the FDA’s accelerated approval pathway, teclistamab is currently approved to treat adult patients with relapsed/refractory MM who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.1 Ongoing approval is contingent on demonstrated clinical benefit in confirmatory trials.

References

1. Tecvayli monotherapy demonstrates superior progression-free and overall survival versus standard of care as early as first relapse in patients with multiple myeloma predominantly refractory to anti-CD38 therapy and lenalidomide. News release. Johnson & Johnson. January 14, 2026. Accessed January 15, 2026. https://www.jnj.com/media-center/press-releases/tecvayli-monotherapy-demonstrates-superior-progression-free-and-overall-survival-versus-standard-of-care-as-early-as-first-relapse-in-patients-with-multiple-myeloma-predominantly-refractory-to-anti-cd38-ther
2. Caffrey M. Time-limited regimens gain notice, offering a break for patients with blood cancer and savings for payers. AJMC®. December 29, 2025. Accessed January 15, 2026. https://www.ajmc.com/view/time-limited-regimens-gain-notice-offering-a-break-for-patients-with-blood-cancer-and-savings-for-payers
3. Shaw ML, Raab MS. Teclistamab shows "tremendous efficacy" in MajesTEC-5 trial: Marc S. Raab, MD, PhD. AJMC. September 30, 2025. Accessed January 15, 2026. https://www.ajmc.com/view/teclistamab-shows-tremendous-efficacy-in-majestec-5-trial-marc-s-raab-md-phd
4. Shaw ML, Raab MS. Exploring Teclistamab’s potential in combination therapy for multiple myeloma: Marc S. Raab, MD, PhD. AJMC. October 29, 2025. Accessed January 15, 2026. https://www.ajmc.com/view/exploring-teclistamab-s-potential-in-combination-therapy-for-multiple-myeloma-marc-s-raab-md-phd
5. Mateos MV, Moreau P, Garfall AL, et al. Teclistamab plus daratumumab in relapsed or refractory multiple myeloma: MajesTEC-3 trial results. N Engl J Med. 2025;393(23). doi:10.1056/NEJMoa2514663
6. A study comparing teclistamab monotherapy versus pomalidomide, bortezomib, dexamethasone (PVd) or carfilzomib, dexamethasone (Kd) in participants with relapsed or refractory multiple myeloma (MajesTEC-9). ClinicalTrials.gov. Updated December 19, 2025. Accessed January 15, 2026. https://clinicaltrials.gov/study/NCT05572515