Results from the MONUMENTAL-3 study showed that the combination of talquetamab and daratumumab with or without pomalidomide (Tal-DP/Tal-D) significantly improved survival compared with daratumumab, pomalidomide, and dexamethasone (DPd) in patients with relapsed or refractory multiple myeloma.
This “represents a new standard of care…as early as [second line] across all practice settings,” according to Peter Voorhees, MD, of Atrium Health/Levine Cancer Institute, and colleagues who presented the findings at the 2026 EHA Congress.
The phase III study included 864 patients who were randomized to receive Tal-DP (n=287), Tal-D (n=387), or DPd (n=290); median age was 64 years, and patients had received a median of two prior lines of therapy.
At a median follow-up of 24.6 months, median progression-free survival (PFS) was significantly improved in the Tal-DP (hazard ratio [HR], 0.28; P<0.0001) and Tal-D (HR, 0.33; P<0.0001) cohorts compared with DPd. The 24-month PFS rates favored Tal-DP (81.3%) and Tal-D (77.6%) versus DPd (51.2%), and the PFS benefit was consistent across subgroups.
The overall response rate was higher in the Tal groups compared with DPd (88.2% and 88.5% vs 77.6%), and measurable residual disease-negative complete response rates or better were significantly higher with Tal-DP (52.3%) and Tal-D (46.3%) compared with DPd (15.9%).
Overall survival also favored the Tal-PD and Tal-D cohorts (HRs, 0.47 and 0.51, respectively).
More patients in the Tal cohorts remained on treatment at data cutoff: 70.3% Tal-DP, 69.7% Tal-D, and 47.3% DPd.
Overall grade 3/4 adverse event rates were 96.7% in the Tal-DP cohort, 78.8% in the Tal-D cohort, and 95.8% in the DPd cohort, with adverse events resulting in treatment discontinuation in 10.5%, 8.0%, and 6.7% of patients, respectively.
Infection rates were similar across the cohorts (87.3%, 84.3%, and 83.0%, respectively). Cytokine release syndrome occurred in 67.8% and 58.4% of Tal-DP and Tal-D patients, while immune effector cell-associated neurotoxicity syndrome occurred in 2.9% and 1.8%, respectively.
Reference
Voorhees P, Mina R, Rodríguez-Otero P, et al. Phase 3, randomized study of talquetamab (TAL) plus daratumumab (DARA) ± pomalidomide (POM) vs DARA plus POM and dexamethasone (DPD) in relapsed/refractory multiple myeloma (RRMM): MONUMENTAL-3. Abstract #2503. Presented at the European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden.
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