J&J talquetamab combo wins CHMP nod for second-line myeloma

Johnson & Johnson has announced that the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended extending the marketing authorisation for TALVEY (talquetamab) to cover its use in combination with daratumumab, with or without pomalidomide, for adults with relapsed or refractory multiple myeloma (RRMM) who have received at least one prior line of therapy.

The recommendation, if adopted by the European Commission as is standard practice, would position the combination as the only GPRC5D-targeting bispecific antibody regimen available as early as second line in Europe. Talquetamab first received conditional marketing authorisation from the EC in August 2023, at that point restricted to patients who had received at least three prior therapies.

MonumenTAL-3 trial results

The CHMP recommendation is grounded in data from the Phase 3 MonumenTAL-3 study (NCT05455320), which enrolled 864 patients with RRMM, all previously exposed to lenalidomide and a proteasome inhibitor. At a median follow-up of approximately 24.6 months, the combination of talquetamab plus daratumumab and pomalidomide (Tal-DP) delivered a progression-free survival (PFS) rate of 81.3% at 24 months, with a hazard ratio of 0.28 versus the comparator arm of daratumumab, pomalidomide and dexamethasone (DPd). The two-drug combination of talquetamab plus daratumumab alone (Tal-D) achieved a 24-month PFS rate of 77.6%, with a hazard ratio of 0.33. Both results were statistically significant (p less than 0.0001).

Overall survival data were also favourable. At 24 months, Tal-DP produced an OS rate of 89.2% (HR 0.47; p equals 0.0006) and Tal-D an OS rate of 87.9% (HR 0.51; p equals 0.0015). Response depth was notable: complete response or better rates reached 71.1% for Tal-DP and 68.9% for Tal-D, compared with 34.5% for DPd. MRD-negative complete response rates similarly favoured the talquetamab arms at 52.3% and 46.3% versus 15.9%.

"MonumenTAL-3 demonstrated significant improvements in progression-free survival, overall survival, response rates and depth of response with the combination of talquetamab and daratumumab," said Ester in 't Groen, EMEA Therapeutic Area Head, Haematology at Johnson & Johnson. "For patients facing their first relapse, this combination has the potential to provide deep responses and keep their disease under control for longer at a critical point in their treatment journey."

On safety, Grade 3/4 treatment-emergent adverse event rates were broadly comparable across arms: 94.9% for Tal-DP, 74.8% for Tal-D and 91.5% for DPd. Tal-D recorded the lowest rate of Grade 3/4 infections at 29.2%. Treatment discontinuation due to adverse events occurred in 10.5% of Tal-DP patients and 8.0% of Tal-D patients, compared with 6.7% in the DPd group.

Competitive and regulatory context

The move into second-line RRMM reflects a broader competitive dynamic in the multiple myeloma market, where a cluster of bispecific antibody programmes are racing to establish earlier treatment positions. Pfizer's elranatamab and Regeneron/Sanofi's isatuximab-based combinations are among the active programmes contesting the BCMA and CD38 space. Talquetamab's GPRC5D target is mechanistically distinct from BCMA, which is the basis of J&J's own ciltacabtagene autoleucel (cilta-cel) CAR-T and several rival bispecifics, and the company argues this distinction supports use in lenalidomide-refractory patients without prior BCMA exposure.

More than 35,000 patients are diagnosed with multiple myeloma annually across the European Union, where the disease remains incurable for most patients and remissions typically shorten with each successive relapse. The availability of an off-the-shelf bispecific combination from second line, if the EC follows the CHMP recommendation, would widen access relative to autologous cell therapies, which carry significant manufacturing lead times and are restricted to specialist centres. The EC decision is expected within roughly two months of the CHMP opinion, in line with standard timelines. J&J said more than 11,000 patients have received talquetamab globally to date.