Johnson & Johnson (NYSE: JNJ) presented Phase III data from the MonumenTAL-3 trial for a combination regimen based around GPRC5D-targeting bispecific T-cell engager talquetamab (Talvey) at the 2026 European Hematology Association Annual Meeting. The data demonstrate that talquetamab in combination with daratumumab with or without pomalidomide produced a 72% reduction in the risk of disease progression or death compared with daratumumab, pomalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM). The results, simultaneously published in the New England Journal of Medicine, represent the first Phase III study to show superior progression-free survival with a GPRC5D-directed bispecific combination in earlier-line disease — a meaningful threshold that had not previously been crossed in randomized data.
The magnitude of the survival benefit is notable. At 24 months, the talquetamab plus daratumumab and pomalidomide (Tal-DP) arm delivered a PFS rate of 81.3% versus 51.2% for the standard-of-care comparator, with the two-drug combination (Tal-D) achieving 77.6%. Overall survival also favored both investigational arms, with 24-month OS rates of 89.2% (Tal-DP) and 87.9% (Tal-D) compared with 79.1% for the control. The 864-patient study enrolled a heavily pretreated population — 85.1% refractory to lenalidomide and 93.4% refractory to their last line of therapy — making the survival separation more clinically consequential. Complete response rates of 71.1% (Tal-DP) and 68.9% (Tal-D) versus 34.5% for DPd, alongside MRD-negative complete response rates of 52.3% and 46.3% versus 15.9%, indicate depth of response well beyond that achieved in the control arm.
At a median follow-up of 24.6 months, both talquetamab-containing regimens maintained durable responses, with more than 70% of patients remaining on treatment at data cutoff versus 47.3% in the control arm. Safety was generally manageable. Cytokine release syndrome was common but predominantly Grade 1–2, while GPRC5D-associated adverse events such as taste changes and weight loss were mostly low grade. Notably, the Tal-D arm was associated with lower rates of Grade 3/4 infections than either Tal-DP or the control regimen.
Competitive context