TALQUETAMAB combined with daratumumab, with or without pomalidomide, significantly improved progression-free survival, overall survival and depth of response compared with daratumumab, pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM), according to interim findings from the Phase 3 MonumenTAL-3 trial presented at EHA 2026 congress.
Talquetamab Trial Delivers Strong Survival Gains
The MonumenTAL-3 study evaluated the GPRC5D-targeting bispecific antibody talquetamab in combination with daratumumab and pomalidomide (Tal-DP) or daratumumab alone (Tal-D) in patients with RRMM who had received at least one prior line of therapy, including lenalidomide and a proteasome inhibitor. The rationale for the trial was based on talquetamab’s B-cell-sparing mechanism and favourable infection profile, which may enable effective combination therapy in earlier treatment settings where durable remissions are a key goal.
The Phase 3 study enrolled 864 patients, who were randomly assigned to Tal-DP, Tal-D or daratumumab, pomalidomide and dexamethasone (DPd). Baseline characteristics were balanced across treatment arms, with a median age of 64 years and a median of two prior lines of therapy. More than 85% of participants were refractory to lenalidomide, and nearly one-third had high-risk cytogenetic features.
Talquetamab Trial Shows Deeper Responses
After a median follow-up of 24.6 months, both talquetamab regimens significantly reduced the risk of disease progression or death compared with DPd. The hazard ratio for progression-free survival was 0.28 for Tal-DP and 0.33 for Tal-D, with both comparisons reaching statistical significance.
The 24-month progression-free survival rates were 81.3% for Tal-DP and 77.6% for Tal-D, compared with 51.2% for DPd. Overall response rates also favoured the talquetamab-containing regimens, reaching 88.2% and 88.5%, respectively, versus 77.6% with DPd. Complete response or better was achieved in more than two-thirds of patients receiving talquetamab, while minimal residual disease-negative complete responses were observed in over 46% of treated patients, substantially exceeding rates seen with the control regimen.
Talquetamab Safety Profile Remains Manageable
Safety findings were broadly consistent with the known profiles of the individual agents. Grade 3 or higher infection rates were comparable to or lower than those observed with DPd, despite high overall infection rates across all groups. Cytopaenias were more frequent with Tal-DP, reflecting the addition of pomalidomide.
Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were predominantly low grade, while GPRC5D-related adverse events such as taste changes and weight loss were generally mild and rarely led to treatment discontinuation. Discontinuation rates remained low across study arms, supporting the feasibility of long-term treatment.
The MonumenTAL-3 interim analysis suggests that talquetamab-based combinations provide substantial efficacy benefits with manageable safety in RRMM. These findings support Tal-D and Tal-DP as potential new standards of care from the second-line setting onwards.
Reference
Voorhees 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 S100. EHA 2026 Congress, 10-14 June, 2026.
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