Patients with multiple myeloma who received a new immunotherapy combination had significantly longer progression-free survival and showed early signs of improved overall survival, according to findings from the phase III MonumenTAL-3 trial.
Peter M. Voorhees, MD, Professor of Medicine at Wake Forest University School of Medicine and a hematologist at Atrium Health Levine Cancer Institute, presented the study’s findings during the Plenary Session at the European Hematology Association 2026 Congress (Abstract S100); the data was also published June 13 in The New England Journal of Medicine.
This phase III trial evaluated a new combination that includes talquetamab, a bispecific antibody targeting GPRC5D and CD3. Researchers compared two talquetamab-based combinations—talquetamab plus daratumumab with or without pomalidomide—to a commonly used standard treatment of daratumumab, pomalidomide, and dexamethasone.
“When multiple myeloma comes back, it can be incredibly difficult for patients and their families,” Dr. Voorhees said. “This study suggests we may be able to offer a treatment to give patients more time, better disease control, and most importantly, renewed hope.”
More than 860 study participants with multiple myeloma that had relapsed after at least one prior treatment took part in the study. Participants were enrolled at more than 180 sites across 18 countries, highlighting the global scope of the trial.
Key Findings
- Longer progression-free survival: About 8 in 10 patients who received a talquetamab-based combination were alive without their cancer progressing 2 years after starting treatment, compared with about 5 in 10 patients receiving standard therapy.
- Stronger treatment responses: Nearly 9 in 10 patients receiving the new combinations saw their cancer shrink, compared with about 8 in 10 on standard treatment.
- Early signs of improved survival: More patients in the talquetamab groups were alive at 2 years compared with those receiving standard care, although longer follow-up is needed to confirm the full survival benefit.
- Improved overall response and measurable residual disease (MRD)-negative complete response: Overall response in the talquetamab groups was approximately 88% vs 77.6% in the standard therapy group; MRD-negative complete response was 52.3% in the talquetamab/daratumumab/pomalidamide group, 46.3% in the talquetamab/daratumumab group, and 34.5% in the standard therapy group.
While patients who received the new treatment regimens still experienced side effects, the study found they were in line with the expected side effects of the individual drugs and relatively few patients required stopping treatment. Some patients experienced changes in taste, decreased weight, and balance issues.
Researchers concluded that these talquetamab-based combinations may represent an important new treatment option for patients with relapsed or refractory multiple myeloma, a setting where new therapies are urgently needed.
Additional studies are underway to better understand long-term survival outcomes and to evaluate how these combinations may be used earlier in treatment.
DISCLOSURE: This study was supported by Johnson & Johnson. For full disclosures of the study authors, visit nejm.com.
