How Tecvayli With Darzalex Works to Treat Multiple Myeloma

CURE recently sat down for an interview with Dr. Surbhi Sidana, chair of the American Society of Hematology’s Committee on Communications and associate professor of medicine at Stanford University, to discuss the treatment combination of Tecvayli (teclistamab) with Darzalex (daratumumab).

The U.S. Food and Drug Administration (FDA) has announced that it granted a national priority review voucher to the pairing for patients with relapsed/refractory multiple myeloma after findings from the MajesTEC-3 clinical trial were published in The New England Journal of Medicine and shared at the 2025 American Society of Hematology Annual Meeting.

Transcript

In patient-friendly terms, how does this treatment combination work to treat multiple myeloma?

This is a combination of an immunotherapy, a bispecific antibody, [Tecvayli], which binds to myeloma cells and brings a patient's own immune killing cells, lymphocytes, close to the myeloma cells so that the lymphocytes can do the killing. It has two arms, one side that binds to the immune cells and the other side that binds to the myeloma cells. [Darzalex] is a monoclonal antibody that identifies a marker on the myeloma cells that's different than [Tecvayli], CD38 and allows, again, direct killing and also immune-mediated killing of the myeloma cell.

So, none of them are chemotherapy. One is a monoclonal antibody, and the other is a bispecific antibody, and then together, they appear to be synergistic, not just additive. And the way we think the synergy works is that [Darzalex] also depletes the body of some immune cells that are not helpful, that might be actually protecting the cancer or preventing the action of these drugs. So I think that is very important, and it's important because when this trial was done, not many patients were exposed to [Darzalex] as frontline therapy. Five percent of patients had prior exposure to [Darzalex] in this trial. Well, now everybody gets [Darzalex] in frontline therapy, and many patients would also be refractory to [Darzalex]. That means their cancer has become resistant to [Darzalex].

That's a big question in the field. Should we be using [Darzalex] in combination with [Tecvayli] for patients who are resistant to [Darzalex]? Will it do something there? And I think the jury is out, but one potential way would be it will still help is to prevent those bad immune cells from interfering with the response. So that's one possibility. So, I think if someone's exposed to [Darzalex], I definitely would not have any hesitation in using [Darzalex] again, but say they were just on [Darzalex] a month or two ago, I think that's where we truly don't know if that would work or not.

References

1. “FDA Proactively Awards National Priority Voucher Based on Strong Phase 3 Study Results,” FDA; https://www.fda.gov/news-events/press-announcements/fda-proactively-awards-national-priority-voucher-based-strong-phase-3-study-results
2. “Tecvayli Treatment Combo Improves Outcomes in Relapsed/Refractory Myeloma,” CURE; https://www.curetoday.com/view/tecvayli-treatment-combo-improves-outcomes-in-relapsed-refractory-myeloma

Transcript has been edited for clarity and conciseness.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.