EHA 2025 – J&J claims an extramedullary edge

Johnson & Johnson is already a dominant multiple myeloma player with its MAb Darzalex, T-cell engagers Tecvayli and Talvey, and Car-T Carvykti, but the company’s next trick could be a Tecvayli/Talvey combo.

At the European Hematology Association congress in Milan, Italy, the company touted data with this pairing from the phase 2 Redirectt-1 study in relapsed/refractory MM with extramedullary disease – an aggressive subtype in which Tecvayli and Talvey monotherapies haven’t impressed.

Among 90 patients, 79% of patients receiving Tecvayli plus Talvey responded, and 54% had a complete response. Results looked just as good in patients who'd previously received BCMA-targeting Car-T, where the ORR was 83%.

By contrast, in extramedullary disease specifically, Tecvayli and Talvey have produced ORRs of 36% and 48% in the Majestec-1 and Monumental-1 trials respectively.

Cross-trial comparison of J&J T-cell engagers in r/r multiple myeloma with extramedullary disease

Note: *with 0.4mg/kg SC weekly dose. Source: EHA 2025 & company communications.

Tecvayli (which hits BCMA) and Talvey (which targets GPRC5D) both have FDA accelerated approval in broad fifth-line MM; Tecvayli based on a 62% ORR in Majestec-1 and Talvey based on a 73% ORR in Monumental-1.

Both compounds have black box warnings for cytokine release syndrome and neurologic toxicity, so these side effects will be worth watching with the combo. J&J said that rates of CRS and ICANS were “mostly low grade”. The company did disclose 10 deaths, but said that five were due to infections, and five were unrelated to therapy.

J&J already has a phase 3 underway, Monumental-6, that combines Tecvayli and Talvey, among other regimens, in relapsed/refractory MM patients who’ve already received Revlimid and an anti-CD38 MAb like Darzalex. Primary completion is due next April.

But J&J already has one eye on the future, with a BCMA and GPRC5D-targeting trispecific T-cell engager, JNJ-79635322, that it reckons could improve potency even compared with a Tecvayli/Talvey combo; early data recently presented at ASCO spurred claims of Car-T-like efficacy.