Tecvayli With Darzalex Could Be ‘Truly Transformative’ in Multiple Myeloma

The U.S. Food and Drug Administration (FDA) recently announced that it had granted a national priority review voucher to Tecvayli (teclistamab) in combination with Darzalex (daratumumab) for patients with relapsed/refractory multiple myeloma, in the wake of findings from the MajesTEC-3 clinical trial being published in The New England Journal of Medicine and shared at the 2025 American Society of Hematology Annual Meeting.

CURE 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 this treatment combination and what its approval by the FDA would mean for patients with multiple myeloma.

CURE: For patients with multiple myeloma, what is the significance of the MajesTEC-3 findings that were presented at ASH in 2025?

Sidana: For those who are not familiar with MajesTEC-3, it's a randomized phase 3 trial of [Darzalex] and [Tecvayli] versus standard of care, which is [Darzalex]-based therapy, [Darxalex and Pomalyst (pomalidomide), DPd, or Velcade (bortezomib), DVd].

The [profession-free survival (PFS)] benefit that we saw was like unprecedented, with significant improvement compared to standard of care, which did just as well, if not slightly better, than expected. And we have not seen this remarkable PFS, a three-year estimate, with anything else. So, for the first time with this combination — that is, except for infections, fairly well tolerated — we are seeing very prolonged remissions in patients. So, I think this is truly transformative.

How would this change the treatment landscape for patients, if this treatment combination is approved by the FDA?

Currently, bispecific antibodies, whether it's [Tecvayli] or other BCMA bispecifics or GPRC5D bispecifics, all of them are approved for late relapse as four-plus lines of therapy. This would be the first bispecific antibody, given it's a combination, to be approved for early relapse. So right now, this increases options for early relapse tremendously.

Right now, we have chemotherapy-based options. We have CAR-T cell therapy, and now this will allow us to use bispecific antibodies. I will say that not everybody is able to access CAR-T cell therapy because they may not live closer to a center, they may not want to travel, even though there's remarkable success in terms of effectiveness and treatment-free interval. But for those patients, this gives an immunotherapy option to them, perhaps closer to home, than CAR-T cell therapy if they don't live close to a center.

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.

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