Teclistamab Improves PFS, OS in First Relapse of Multiple Myeloma

Teclistamab-cqyv (Tecvayli) demonstrated superior progression-free survival (PFS) and overall survival (OS) compared with standard-of-care (SOC) triplet or doublet therapies in patients who have received 1 to 3 prior lines of therapy for multiple myeloma, according to recently reported topline results.¹

In the first prespecified interim analysis of the phase 3 MajesTEC-9 trial (NCT05572515),2 teclistamab resulted in a 71% reduction in progression or death (HR, 0.29; 95% CI, 0.23–0.38) and a 40% reduction in the risk of death (HR, 0.60; 95% CI, 0.43–0.833).¹

“The MajesTEC-9 results reinforce the potential of [teclistamab] 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 at Winship Cancer Institute of Emory University, in a news release. “The impressive results show a significant improvement in [PFS] and [OS] as a monotherapy in patients with refractory multiple myeloma, and together with the MajesTEC-3 [NCT05083169] results, help establish [teclistamab] as an essential therapy for patients as early as first relapse.”

The randomized phase 3 MajesTEC-9 trial enrolled an estimated 614 patients in 210 locations worldwide to receive teclistamab or a SOC regimen of pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone or carfilzomib (Kyprolis) plus dexamethasone.¹ Patients must have received prior anti-CD38 antibody and lenalidomide (Revlimid), and the majority (85% and 79%) were refractory to these respective agents. Over 90% were refractory to their last line of therapy.

The primary end points were PFS and the occurrence of cytokine release syndrome by number and severity. Secondary end points included OS, overall response rate, duration of response, time to next treatment, and quality of life measures.

No new safety signals were observed with teclistamab, and the safety outcomes were consistent with its known safety profile.

Based on these data, the data monitoring committee recommended unblinding of the study, and full results of this analysis will be presented at a future medical meeting.

About Teclistamab

The bispecific T-cell engager teclistamab received accelerated approval in 2022 based on the single-arm MajesTEC-1 trial (NCT03145181; NCT04557098) in patients who had received at least 4 prior lines of therapy including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody.³

In December 2025 at the 67th ASH Annual Meeting, data from the landmark MajesTEC-3 study showed that teclistamab plus daratumumab significantly improved OS and PFS vs standard daratumumab-based regimens in patients with relapsed/refractory multiple myeloma who had received 1 to 3 prior lines of therapy. The 36-month OS rate was 83.3% with the combination vs 65.0% with patients receiving investigator’s choice of subcutaneous daratumumab plus dexamethasone and either pomalidomide or bortezomib. Teclistamab and daratumumab reduced the risk of death by 54% vs the control arm (HR, 0.46; 95% CI, 0.32-0.65; P <.0001).

Based on the MajesTEC-3 trial results, it earned an FDA priority voucher in combination with daratumumab and hyaluronidase-fihj (subcutaneous daratumumab; Darzalex Faspro) in December 2025 for patients as early as the second line.⁵

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://tinyurl.com/kvppbavu

2. 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

3. FDA approves teclistamab-cqyv for relapsed or refractory multiple myeloma. News release. US FDA. October 25, 2022. Accessed January 15, 2026. https://tinyurl.com/2s3j9an2

4. 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

5. Tecvayli plus Darzalex Faspro combination selected for commissioner’s National Priority Voucher Pilot Program. News release. Johnson & Johnson. December 15, 2025. Accessed January 15, 2026. https://tinyurl.com/3kdvybyv