Teclistamab/Talquetamab Reduces Risk of Progression by 89% in R/R Multiple Myeloma

Teclistamab-cqyv (Tecvayli) plus talquetamab-tgvs (Talvey) significantly reduced the risk of disease progression or death compared with investigator’s choice of standard-of-care therapy in patients with relapsed or refractory multiple myeloma (R/R MM), according to a news release.¹

Topline results from the phase 3 MonumenTAL-6 trial (NCT06208150) showed that the dual antigen regimen targeting B-cell maturation antigen (BCMA) and GPRC5D resulted in an 89% reduction of progression or death and a 62% reduction in risk of death in patients who received 1 to 4 prior lines of therapy including a prior anti-CD38 antibody and lenalidomide (Revlimid). The results led to the independent review committee (IRC) recommending unblinding of the study at the first interim analysis.

“[Teclistamab and talquetamab] together generated deep and durable responses, demonstrating what’s possible by targeting BCMA and GPRC5D at the same time, and further reinforcing the potential of this off-the-shelf regimen to improve outcomes for patients across practice settings.” Ajay K. Nooka, MD, MPH, FACP, director of the Myeloma Program in the Department of Hematology and Medical Oncology at Emory University School of Medicine, stated in the news release.

Trial Design and Topline Results

MonumenTAL-6 is a global, randomized, 3-arm study evaluating teclistamab plus talquetamab (Tec-Tal) and talquetamab plus pomalidomide (Pomalyst; Tal-P) against investigator’s choice of either elotuzumab (Empliciti), pomalidomide, and dexamethasone (EPd) or pomalidomide, bortezomib (Velcade), and dexamethasone (PVd) in adult patients with R/R MM who had received 1 to 4 prior lines of therapy, including an anti-CD38 antibody and lenalidomide. The primary end point is progression-free survival (PFS) as assessed by IRC; key secondary end points include overall response rate, complete response or better, minimal residual disease–negative complete response, and overall survival (OS).

Both investigational arms met the study’s primary end point, demonstrating statistically significant and clinically meaningful improvements in PFS compared with standard of care. The Tec-Tal regimen reduced the risk of progression or death by 89% (HR, 0.11; 95% CI, 0.08-0.16; P <.0001), whereas the Tal-P regimen reduced this risk by 73% (HR, 0.27; 95% CI, 0.20-0.35). According to the news release, the Tec-Tal HR represents the lowest seen across any phase 3 study evaluating bispecific therapies in R/R MM to date.

Both arms also showed statistically significant and clinically meaningful improvements in OS compared with standard of care, with Tec-Tal reducing the risk of death by 62% (HR, 0.38). The overall safety profiles of both combination arms were consistent with the known safety profiles of each individual therapy.

Full results are expected to be presented at a future major medical meeting and shared with global health authorities.

Context of Findings

According to Johnson & Johnson, MonumenTAL-6 represents the fifth positive phase 3 study evaluating the company’s multiple myeloma T-cell–engaging therapy portfolio in the second-line setting, reflecting a broader effort to move immunotherapy-based combinations earlier in the multiple myeloma treatment course.

Both teclistamab and talquetamab have proven highly effective in relapsed/refractory multiple myeloma alone and in combinations with other agents across multiple trials. The Tal-P regimen previously showed strong efficacy in the phase 1b MonumenTAL-2 trial (NCT05050097) including responses in all patients who received prior pomalidomide or chimeric antigen receptor (CAR) T-cell therapy.² Teclistamab plus daratumumab (Darzalex) was approved in the second line and beyond,³ whereas teclistamab monotherapy demonstrated a 71% reduction in progression or death vs standard-of-care in R/R MM in the MajesTEC-9 trial (NCT05572515).⁴ Talquetamab, pomalidomide, and daratumumab as well as talquetamab plus daratumumab were associated with strong PFS benefit vs daratumumab, pomalidomide, and dexamethasone in the MonumenTAL-3 trial.⁵

“These findings add to a growing body of phase 3 evidence evaluating the survival outcomes associated with the early use of immunotherapy doublets in the treatment journey,” Nooka stated in the news release.

REFERENCES

1. TECVAYLI® + TALVEY® reduced the risk of disease progression or death by 89% and the risk of death by 62% in earlier-line relapsed/refractory multiple myeloma. News release. Johnson & Johnson. July 23, 2026. Accessed July 23, 2026. https://tinyurl.com/y5353t7y

2. Quach H, Perrot A, Matous J, et al. Talquetamab, a GPRC5D×CD3 bispecific antibody, in combination with pomalidomide in patients with Relapsed/Refractory multiple myeloma: Updated safety and efficacy results from the Phase 1b MonumenTAL-2 study. Blood. 2025;146(suppl 1):2282. doi:10.1182/blood-2025-2282

3. FDA approves teclistamab in combination with daratumumab hyaluronidase-fihj for relapsed or refractory multiple myeloma. FDA. March 5, 2026. Accessed July 23, 2026. https://tinyurl.com/mry968za

4. Mina R, Touzeau C, Hungria V, et al. MajesTEC-9: a phase 3 randomized study of teclistamab monotherapy vs investigator's choice of pomalidomide, bortezomib, and dexamethasone or carfilzomib and dexamethasone (PVd/Kd) in patients with relapsed refractory multiple myeloma. Presented at: 2026 American Society of Clinical Oncology Annual Meeting; May 29-June 2, 2026; Chicago, IL.

5.Voorhees PM, Mina R, Rodríguez-Otero P, et al. Phase 3, randomized study of talquetamab plus daratumumab ± pomalidomide vs daratumumab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: MonumenTAL-3. Presented at: the European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S100.