Clinical Summary: 

• Design/Population: The phase 3 MonumenTAL-3 trial compared talquetamab containing regimens against daratumumab plus pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma who had received at least 1 prior line of therapy.
• Key Outcomes: Both talquetamab-based regimens significantly improved progression-free survival, overall survival, response, and MRD negativity compared with daratumumab plus pomalidomide and dexamethasone. 
• Clinical Relevance: These findings support talquetam-based combinations as a potential new standard of care for relapsed or refractory multiple myeloma as early as second-line treatment.

Results from the phase 3 MonumenTAL-3 trial demonstrated that talquetamab-based regimens significantly improved survival compared with daratumumab plus pomalidomide and dexamethasone among patients with relapsed or refractory multiple myeloma. 

These results were presented by Peter Voorhees, MD, Levine Cancer Institute, Charlotte, North Carolina, at the 2026 European Hematology Association (EHA) Congress in Stockholm, Sweden. 

In this study, 864 patients who received ≥1 prior line of therapy, including lenalidomide and a proteasome inhibitor, were randomized 1:1:1 to receive either talquetamab plus daratumumab and pomalidomide (n = 287), talquetamab plus daratumumab (n = 287), or daratumumab plus pomalidomide and dexamethasone (n = 290). The primary end point was investigator-assessed progression-free survival (PFS). Key secondary end points included overall response rate (ORR), complete response or better, minimal residual disease (MRD) negativity, overall survival (OS), and safety.

At a median follow-up of 24.6 months, the 24-month PFS rate was 81.3% in the talquetamab plus daratumumab and pomalidomide arm, 77.6% in the talquetamab plus daratumumab arm, and 51.2% in the daratumumab plus pomalidomide and dexamethasone arm (P < .001). This benefit was observed across clinically relevant subgroups. The ORRs were 88.2%, 88.5%, and 77.6%, respectively. 

Complete response or better was achieved in 71.1% of patients in the talquetamab plus daratumumab and pomalidomide arm, 69% of patients in the talquetamab plus daratumumab arm, and 34.5% of patients in the daratumumab plus pomalidomide and dexamethasone arm. MRD-negative complete response was achieved in 52.3%, 46.3%, and 15.9% of patients, respectively. At interim analysis, both talquetamab plus daratumumab and pomalidomide (P = .0006) and talquetamab plus daratumumab (P = .0015) were associated with significant OS improvements. 

At the data cutoff point, treatment was ongoing in 70.3% of patients in the talquetamab plus daratumumab and pomalidomide arm, 69.7% of patients in the talquetamab plus daratumumab arm, and 47.3% of patients in the daratumumab plus pomalidomide and dexamethasone arm. 

Adverse events were generally consistent with the known safety profiles of the individual agents. Grade 3/4 adverse events were reported in 96.7% of patients in the talquetamab plus daratumumab and pomalidomide arm, 78.8% of patients in the talquetamab plus daratumumab arm, and 95.8% of patients in the daratumumab plus pomalidomide and dexamethasone arm. Grade 3/4 infection rates were 37%, 27.7%, and 41%, respectively. 

Cytokine release syndrome was primarily grade 1/2 and was reported in 67.8% of patients in the talquetamab plus daratumumab and pomalidomide arm and 58.4% of patients in the talquetamab plus daratumumab arm. Immune effector cell-associated neurotoxicity syndrome was reported in 2.9% and 1.8% of patients, respectively.

“[Talquetamab plus daratumumab] with or without [pomalidomide] represents a new standard of care for [relapsed or refractory multiple myeloma] as early as 2L across all practice settings,” concluded Dr Voorhees. 

Source:

Voorhees P, Mina R, Rodriguez-Otero P, et al. Phase 3 randomized study of talquetamab (Tal) plus daratumumab (Dara) with or without pomalidomide (Pom) vs daratumumab plus pomalidomide and dexamethasone (DPd) in relapsed/refractory multiple myeloma (RRMM): MonumenTAL-3. Presented at EHA Congress. June 11 - June 14, 2026. Stockholm, Sweden. Abstract EHA-2503.