Teclistamab Combos Improve PFS, OS in Relapsed/Refractory Multiple Myeloma

Teclistamab-cqyv (Tecvayli) plus talquetamab-tgvs (Talvey), a dual BCMA- and GPRC5D-targeting regimen, and talquetamab plus pomalidomide (Pomalyst) each significantly improved progression-free survival (PFS) and overall survival (OS) compared with standard of care in patients with relapsed or refractory multiple myeloma who received 1 to 3 prior lines of treatment, meeting the primary end point of the phase 3 MonumenTAL-6 trial (NCT06208150), according to a news release from Johnson & Johnson.¹ The teclistamab plus talquetamab (Tec-Tal) arm delivered the greatest benefit among the 2 investigational regimens.

What did MonumenTAL-6 show?

Both the Tec-Tal and talquetamab plus pomalidomide (Tal-P) regimens met the primary end point of PFS, with statistically significant and clinically meaningful improvements vs standard of care. The Tec-Tal arm reduced the risk of disease progression or death by 89% (HR, 0.11; 95% CI, 0.08-0.16; P <.0001) and the risk of death by 62% (HR, 0.38), which the developer described as the lowest HR observed across any phase 3 study in this setting. The Tal-P arm reduced the risk of progression or death by 73% (HR, 0.27; 95% CI, 0.2-0.35).

The safety profiles in both investigational arms were consistent with the known profiles of each agent as monotherapy. Based on the strength of the data, the independent data monitoring committee recommended unblinding the study at the first interim analysis.

Developers noted that full results will be presented at a future medical meeting and shared with global health authorities.

“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,” said Ajay K. Nooka, MD, MPH, director of the Myeloma Program in the Department of Hematology and Medical Oncology at Emory University School of Medicine, in the press release.¹ “[Teclistamab plus 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.”

What is the MonumenTAL-6 trial design?

MonumenTAL-6 is a global, randomized, 3-arm phase 3 study evaluating Tec-Tal and Tal-P vs investigator’s choice of either elotuzumab (Empliciti), pomalidomide, and dexamethasone (EPd) or pomalidomide, bortezomib (Velcade), and dexamethasone (PVd) in patients with relapsed/refractory multiple myeloma who have received 1 to 4 prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide. The primary end point is PFS as assessed by an independent review committee.² Key secondary end points include overall response rate, complete response or better rate, minimal residual disease–negative complete response rate, and OS.

What are teclistamab and talquetamab?

Teclistamab is a first-in-class, BCMA-directed CD3 T-cell engager bispecific antibody, and talquetamab is a first-in-class GPRC5D-directed CD3 T-cell engager bispecific antibody. Both agents are approved as off-the-shelf therapies for relapsed/refractory multiple myeloma.

MonumenTAL-6 is the first phase 3 study to evaluate a dual-antigen regimen combining BCMA- and GPRC5D-targeting bispecific antibodies in relapsed/refractory multiple myeloma. Teclistamab is indicated for adults with relapsed/refractory multiple myeloma after at least 1 prior line of therapy in combination with daratumumab and hyaluronidase-fihj (Darzalex Faspro).³ Talquetamab previously received accelerated approval for patients who have received at least 4 prior lines of therapy.⁴ Both agents are available only through a shared Risk Evaluation and Mitigation Strategy program because of the risks of cytokine release syndrome and neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome.

“These findings further reinforce immunotherapy as a cornerstone of multiple myeloma care and strengthen the growing body of evidence supporting our leadership in this space. By continuing to expand treatment options across the disease continuum, we are moving closer to our ambition of one day curing this disease,” Yusri Elsayed, MD, MHSc, PhD, global therapeutic area head of Oncology at Johnson & Johnson, concluded.¹

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/3ee86wxk
2. A study comparing talquetamab plus pomalidomide, talquetamab plus teclistamab, and elotuzumab, pomalidomide, and dexamethasone or pomalidomide, bortezomib, and dexamethasone in participants with relapsed or refractory myeloma who have received an anti-CD38 antibody and lenalidomide (MonumenTAL-6). ClinicalTrials.gov. Updated June 5, 2026. Accessed July 23, 2026. https://tinyurl.com/2tacpycx
3. FDA grants third approval under the National Priority Voucher Program. News release. FDA. March 5, 2026. Accessed July 23, 2026. https://tinyurl.com/45hhbpau
4. U.S. FDA approved TALVEY (talquetamab-tgvs), a first-in-class bispecific therapy for the treatment of patients with heavily pretreated multiple myeloma. News release. The Janssen Pharmaceuticals. August 10, 2023. Accessed July 23, 2026. https://prn.to/3KwnjyD