EU Regulators Back Earlier Use of Talvey Plus Daratumumab in Multiple Myeloma: What the Phase 3 MonumenTAL-3 Data Actually Show

On October 16, 2026, the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) recommended expanding the approved use of Johnson & Johnson's bispecific antibody Talvey (talquetamab), combined with daratumumab, to patients with relapsed or refractory multiple myeloma who have had just one prior line of therapy — a substantially earlier point in treatment than its current approval allows. The recommendation is backed by strong, mature Phase 3 data, and it's a genuinely encouraging development for a blood cancer that remains incurable for most patients. Here's what the trial actually found, and what comes next.

What Changed, and Why It Matters

Talquetamab is a bispecific T-cell engaging antibody — a lab-made molecule that binds simultaneously to CD3 on a patient's own T-cells and to GPRC5D, a protein highly expressed on multiple myeloma cells but largely absent from healthy B-cells. In practical terms, it works by physically dragging T-cells into contact with myeloma cells and triggering an immune attack. Daratumumab, a long-established myeloma drug, targets a different protein, CD38, and appears to further sensitize the immune system to talquetamab's effect when the two are combined. Talquetamab already carries conditional EU and accelerated FDA approval as a standalone drug for heavily pretreated patients who've exhausted several other treatment lines. The new CHMP recommendation would move the daratumumab combination much earlier — to patients who've had just one prior therapy — meaning, if finalized, far more myeloma patients could access it sooner in their treatment course, before the disease has had as many chances to become treatment-resistant.

What the MonumenTAL-3 Trial Found

The recommendation rests on MonumenTAL-3 (NCT05455320), a Phase 3 trial that randomized 864 patients with relapsed or refractory multiple myeloma to one of three arms: talquetamab plus daratumumab and pomalidomide (Tal-DP), talquetamab plus daratumumab alone (Tal-D), or the standard-of-care combination of daratumumab, pomalidomide, and dexamethasone (DPd). At a median follow-up of roughly two years, both talquetamab combinations sharply outperformed standard care. Progression-free survival was dramatically better: the risk of progression or death was reduced by about 72% with Tal-DP (hazard ratio 0.28) and about 67% with Tal-D (hazard ratio 0.33), both highly statistically significant. At 24 months, 81.3% of patients on Tal-DP and 77.6% on Tal-D had not progressed, compared with a substantially lower rate on standard treatment. Overall survival also favored both talquetamab combinations, with roughly a 50% reduction in the risk of death and 24-month survival rates near 88–89%. Response rates were similarly strong — about 88% of patients responded to either talquetamab combination, versus 77.6% on standard care — and deep responses were notably more common: 71.1% (Tal-DP) and 68.9% (Tal-D) achieved a complete response or better, compared with 34.5% on standard treatment, and roughly half of talquetamab-treated patients reached undetectable disease by sensitive molecular testing (MRD-negativity), versus about 16% on standard care.

The Caveats That Still Apply

This is a recommendation, not a final approval — the European Commission's decision typically follows within about two months of a positive CHMP opinion, and it isn't guaranteed. The safety profile also isn't free of trade-offs: serious (grade 3 or 4) side effects were more common with the triple combination (Tal-DP, at 94.9%) than with the standard regimen (91.5%) or the two-drug talquetamab combination (Tal-D, at 74.8%), and infections — a known risk with T-cell engaging therapies and an expected consequence of suppressing myeloma cells that also support normal antibody production — occurred in the majority of patients across all three arms. Fatal adverse events were actually less frequent with both talquetamab arms (1.8% and 4.0%) than with standard care (4.6%), though these are small percentage differences in a relatively short follow-up window. As with any T-cell engaging bispecific, talquetamab carries labeled risks for cytokine release syndrome and neurologic side effects that require specialized monitoring, particularly during the first doses.

Bottom Line

The MonumenTAL-3 data represent a genuinely strong result — more than halving the risk of disease progression and meaningfully extending survival compared with standard treatment — and the CHMP's recommendation could bring that benefit to patients much earlier in their myeloma journey, pending final European Commission approval. The combination isn't risk-free, and multiple myeloma remains, for now, a chronic and largely incurable disease even with these advances, but mature, randomized, placebo-controlled-style data of this magnitude is exactly the kind of evidence that earns cautious optimism in oncology.