Johnson & Johnson’s Phase 3 MonumenTAL-3 trial showed talquetamab combinations reduced progression risk by up to 72% and improved survival outcomes in relapsed or refractory multiple myeloma.
Written By: Fariha Sameen, PharmD
Reviewed By: Pharmacally Editorial Team
Johnson & Johnson reported positive results from the global Phase 3 MonumenTAL-3 trial (NCT05455320) showing that TALVEY® (talquetamab-tgvs) combined with DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj), with or without pomalidomide, significantly improved progression-free survival, overall survival, and depth of response in patients with relapsed or refractory multiple myeloma (RRMM).
The findings, presented at the 2026 European Hematology Association (EHA) Congress and published simultaneously in The New England Journal of Medicine, mark the first Phase 3 demonstration of a GPRC5D-targeting bispecific antibody combination in earlier-line multiple myeloma.
Trial Design and Patient Population
The MonumenTAL-3 study enrolled 864 patients with RRMM who had received at least one prior line of therapy, including lenalidomide and a proteasome inhibitor. More than 85% of participants were refractory to lenalidomide and over 93% were refractory to their most recent treatment, reflecting a heavily pretreated and difficult-to-treat population.
Patients were randomized to receive talquetamab plus daratumumab and pomalidomide (Tal-DP), talquetamab plus daratumumab (Tal-D), or the standard regimen of daratumumab, pomalidomide, and dexamethasone (DPd).
Efficacy Outcomes
At a median follow-up of 24.6 months, Tal-DP reduced the risk of disease progression or death by 72% compared with DPd (HR 0.28; p<0.0001), while Tal-D reduced risk by 67% (HR 0.33; p<0.0001).
Progression-free survival rates at 24 months reached 81.3% with Tal-DP and 77.6% with Tal-D, compared with 51.2% for DPd. The benefit extended to overall survival, with rates of 89.2%, 87.9%, and 79.1%, respectively.
Both talquetamab-containing regimens also produced deeper responses than standard therapy. Overall response rates reached 88.2% with Tal-DP and 88.5% with Tal-D versus 77.6% with DPd. Complete response or better rates exceeded 68% in both investigational arms compared with 34.5% for standard therapy.
Minimal residual disease (MRD)-negative complete response rates reached 52.3% with Tal-DP and 46.3% with Tal-D, compared with 15.9% for DPd, demonstrating substantially deeper disease clearance.
Safety Profile
The safety profile was consistent with the known profiles of the individual agents. Grade 3 or 4 treatment-emergent adverse events occurred in 94.9% of patients receiving Tal-DP, 74.8% receiving Tal-D, and 91.5% receiving DPd.
Although overall infection rates were similar across treatment groups, severe infections occurred less frequently with Tal-D than with standard therapy. Cytokine release syndrome occurred in 67.8% of patients receiving Tal-DP and 58.4% receiving Tal-D but was predominantly Grade 1 or 2. Immune effector cell-associated neurotoxicity syndrome (ICANS) was uncommon, affecting fewer than 3% of patients, with no Grade 4 or higher events reported.
Taste changes, weight loss, and balance disorders were largely low grade and rarely led to treatment discontinuation. At the data cutoff, approximately 70% of patients receiving talquetamab-based regimens remained on therapy compared with 47.3% of patients receiving DPd.
Regulatory Path Forward
Peter Voorhees, MD, of Atrium Health Levine Cancer Institute, said the results highlight the potential of introducing talquetamab combinations earlier in the treatment course, where highly active therapies may provide the greatest benefit.
Based on the Phase 3 findings, Johnson & Johnson has submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration and a Type II variation application to the European Medicines Agency seeking approval of talquetamab plus daratumumab, with or without pomalidomide, for patients with RRMM after at least one prior line of therapy.
If approved, the regimen could become the first GPRC5D-targeting bispecific antibody combination available for patients earlier in the multiple myeloma treatment journey, potentially expanding the role of bispecific immunotherapy beyond late-line settings.
References
About the Writer
Fariha Sameen, PharmD (LinkedIn), is a clinical pharmacy professional with hands-on experience in patient counselling, medication review, therapeutic monitoring, and clinical documentation across multiple departments. She has experience identifying and assessing drug-related problems and supporting medication safety practices. Her interests include pharmacovigilance, ADR reporting, clinical research, and medical writing focused on clear, evidence-based communication.