J&J talquetamab plus daratumumab cuts RRMM death risk by up to 53%

Johnson & Johnson has presented Phase 3 data showing that talquetamab (Talvey) combined with daratumumab, with or without pomalidomide, significantly outperformed a standard daratumumab-pomalidomide-dexamethasone regimen in patients with relapsed or refractory multiple myeloma (RRMM) who had received at least one prior line of therapy. Results were presented at the European Hematology Association Annual Meeting in Stockholm and published simultaneously in the New England Journal of Medicine.

The MonumenTAL-3 study (NCT05455320) enrolled 864 patients, all of whom had prior exposure to lenalidomide and a proteasome inhibitor. At a median follow-up of approximately 24.6 months, the talquetamab-daratumumab-pomalidomide arm (Tal-DP) reduced the risk of progression or death by 72% versus standard care (hazard ratio 0.28; 95% CI 0.20-0.40; p less than 0.0001). The talquetamab-daratumumab arm (Tal-D) reduced that risk by 67% (HR 0.33; 95% CI 0.24-0.46). Two-year progression-free survival rates reached 81.3% for Tal-DP and 77.6% for Tal-D, compared with 51.2% for the control arm. Overall survival at 24 months was 89.2% and 87.9% respectively, against 79.1% for standard care.

Clinical findings

Response depth was also notably improved. Complete response or better rates were 71.1% for Tal-DP and 68.9% for Tal-D versus 34.5% for the control. MRD-negativity at the 10-5 threshold reached 52.3% and 46.3% in the investigational arms, compared with 15.9% for DPd. Rates of Grade 3 or 4 adverse events were broadly comparable across arms at around 75-95%, though severe infection rates were lower with Tal-D (29.2%) than with the standard regimen (42.2%). Cytokine release syndrome occurred in the majority of bispecific-treated patients but was predominantly Grade 1 or 2. Class-characteristic side effects including taste changes and weight loss were common but rarely prompted treatment discontinuation.

Peter Voorhees, Professor of Hematology and Oncology at Atrium Health's Levine Cancer Institute, said: "Talquetamab works with daratumumab in earlier lines, a critical time for treating patients with the most effective regimens." Voorhees disclosed consulting and advisory relationships with Johnson & Johnson.

J&J submitted a Type II variation to the European Medicines Agency on 31 March 2026, seeking to extend talquetamab's label to include combination use with daratumumab, with or without pomalidomide. Talquetamab currently holds conditional marketing authorisation in the EU for heavily pre-treated RRMM patients who have received at least three prior therapies. The FDA approved the drug on an accelerated basis in August 2023 for patients with at least four prior lines.

Market context

MonumenTAL-3 is the third Phase 3 positive readout from J&J's bispecific portfolio in recent months, following data for its BCMA-targeting bispecific teclistamab from both the ASCO and ASH conferences. The results collectively reinforce J&J's strategy of moving bispecific antibodies into earlier treatment lines, where patient numbers and commercial opportunity are considerably larger than in the heavily pre-treated salvage setting.

Multiple myeloma remains one of the most competitive spaces in oncology. Bispecific antibodies from several large-pharma and mid-cap developers are progressing through trials, with BCMA-directed agents from Pfizer and others also seeking earlier-line positioning. GPRC5D, the target talquetamab binds alongside CD3 on T cells, is mechanistically distinct from BCMA and expressed at low or absent levels on normal B cells, offering a differentiated resistance profile for patients who have progressed on BCMA-directed therapy. Whether regulators grant full approval on the basis of MonumenTAL-3, and whether payers accept the combination's cost profile, will determine how quickly the label expansion translates into commercial uptake across European markets. More than 35,000 patients are diagnosed with multiple myeloma annually in the EU, and daratumumab-based regimens are already deeply embedded across treatment lines, giving the talquetamab combination a strong commercial foundation to build on.