EHA 2026 preview – a Monumental boost to J&J’s Talvey hopes

Any doubts about the Monumental-3 trial of Johnson & Johnson’s Talvey in second-line-plus multiple myeloma, spurred by the company choosing not to topline it, have been blown out of the water.

A recently released plenary abstract from the European Hematology Association congress shows a convincing progression-free survival benefit with Talvey when added to Darzalex, with or without Pomalyst, versus Darzalex and Pomalyst alone. The hazard ratios are impressive, at 0.28 for the triplet and 0.33 for the doublet.

Though efficacy looked better with the triplet, this was also associated with a much higher rate of grade 3 and 4 cytopenias, at 88% versus 52% for the doublet. The investigators noted that this was to be expected with Pomalyst; indeed, the control group also saw high cytopenia rates.

This raises the question of whether the doublet or triplet will ultimately be approved and, if both get the nod, which would be more widely used by doctors.

Tangled web

Another question is how Talvey fits into J&J’s increasingly complicated web of multiple myeloma therapies. The GPRC5D-targeting T-cell engager currently has FDA accelerated approval in patients with four prior therapies, including a proteasome inhibitor, an immunomodulatory agent like Revlimid, and an anti-CD38 monoclonal antibody like Darzalex.

Talvey now looks likely to move earlier in the treatment paradigm – but two J&J BCMA-targeted therapies, the T-cell engager Tecvayli and the Legend-partnered Car-T Carvykti, have already got there.

Tecvayli notably recently got the green light, alongside Darzalex, in second-line plus patients who had previously received a proteasome inhibitor and/or an immunomodulatory agent, based on the Majestec-3 trial.

This setting is similar to Monumental-3. Still, Majestec-3 looked more impressive on a cross-trial basis, with Tecvayli plus Darzalex producing a PFS hazard ratio of 0.17 versus control (Darzalex plus dexamethasone and either Pomalyst or Velcade).

Tecvayli also looks likely to expand into the post-Darzalex setting, on the back of the Majestec-9 trial, which was toplined positive in January, and is set to be presented at ASCO. J&J has said it plans to file Tecvayli with the FDA for this use in 2026.

The company also has another post-Darzalex trial, Monumental-6, testing Talvey plus either Tecvayli or Pomalyst.

Carvykti, meanwhile, got the FDA go-ahead in second-line disease in April 2024, and is currently the best selling of the three products, with first-quarter revenues of $597m, compared with Tecvayli’s $202m and Talvey’s $152m.

Ultimately, J&J has said that use will come down to patient choice – but the group could end up cannibalising its own drugs.

Monumental-3 results

Source: EHA abstract.