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 multiple myeloma with extramedullary disease – an aggressive subtype in which Tecvayli and Talvey monotherapies haven’t impressed.

Among 90 patients, 79% receiving Tecvayli plus Talvey responded, and 54% had a complete response. Results looked just as good in subjects who had previously received BCMA-targeting Car-T, where the ORR was 83%.

By contrast, in extramedullary disease specifically, Tecvayli and Talvey have produced ORRs of 43% and 44% in the Majestec-1 and Monumental-1 trials respectively, according to slides presented at EHA.

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

Source: EHA 2025 & company communications.

Tecvayli (which hits BCMA) and Talvey (GPRC5D) both have FDA accelerated approvals in broad fifth-line multiple myeloma, 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. Still, there were no cases of grade 3 or higher CRS, and only two cases of grade 3 or 4 ICANS. There were 10 deaths, with five due to infections. Of the other five, four were deemed unrelated, and one related, due to "aspiration". Rates of severe infections were similar to monotherapy, J&J said.

J&J already has a phase 3 trial under way, Monumental-6, that combines Tecvayli and Talvey, among other regimens, in relapsed/refractory multiple myeloma patients who have already received Revlimid and an anti-CD38 MAb like Darzalex. Primary completion is 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. 

This story has been updated.