FDA Approves Zenbexus Combination for Patients With Multiple Myeloma After Prior Treatment

The Food and Drug Administration granted accelerated approval on Aug. 13, 2026, to Zenbexus (iberdomide) in combination with daratumumab and hyaluronidase-fihj and dexamethasone for adults with multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent.

The decision means patients whose myeloma has returned or stopped responding after earlier treatment now have another approved regimen available to them. The approval was supported by results from the EXCALIBER-RRMM trial, in which the Zenbexus-based combination doubled the rate of a key measure of deep response compared with a standard four-drug alternative. Full prescribing information for Zenbexus will be posted on Drugs@FDA.

What Data Supported the FDA Approval of Zenbexus for Multiple Myeloma?

The main measure of effectiveness in EXCALIBER-RRMM was minimal residual disease-negative complete response at any time. Minimal residual disease refers to the small number of myeloma cells that can remain in the body after treatment, and a minimal residual disease-negative complete response means that testing could no longer detect those cells.

The primary efficacy population included the first 420 patients randomly assigned to receive Zenbexus at 1 milligram in combination with daratumumab and hyaluronidase-fihj and dexamethasone, referred to as Dd, or to the comparison group of daratumumab and hyaluronidase-fihj, bortezomib and dexamethasone, referred to as DVd, across both stages of the trial. Of those patients, 207 received the Zenbexus-containing regimen and 213 received the comparison regimen.

The minimal residual disease-negative complete response rate at any time was 41% among patients treated with Zenbexus plus daratumumab and hyaluronidase-fihj and dexamethasone, compared with 21% among patients treated with the daratumumab and hyaluronidase-fihj, bortezomib and dexamethasone regimen. The difference between the two groups was statistically significant, with a p-value of less than 0.0001, meaning it was unlikely to be due to chance.

How Was the EXCALIBER-RRMM Trial Designed?

EXCALIBER-RRMM was a two-stage, randomized, multicenter, open-label trial that enrolled adults with relapsed or refractory multiple myeloma who had previously received one or two prior lines of therapy. Open-label means that patients and their care teams knew which treatment was being given.

A total of 939 patients took part. In stage 1, 279 patients were assigned to one of three dose levels of Zenbexus in combination with daratumumab and hyaluronidase-fihj and dexamethasone, or to the daratumumab and hyaluronidase-fihj, bortezomib and dexamethasone regimen. In stage 2, 660 patients were assigned to Zenbexus at 1 milligram in combination with daratumumab and hyaluronidase-fihj and dexamethasone, or to the comparison regimen.

Patients whose disease was refractory to a prior anti-CD38 monoclonal antibody therapy, or to prior bortezomib, were not eligible to enroll.

The recommended dose of Zenbexus is 1 milligram taken by mouth once daily, with or without food, on days 1 through 21 of a 28-day cycle, given in combination with daratumumab and hyaluronidase-fihj and dexamethasone. Daratumumab and hyaluronidase-fihj is given under the skin at 1,800 milligrams on days 1, 8, 15 and 22 of cycles 1 through 2; days 1 and 15 of cycles 3 through 6; and day 1 of cycle 7 and beyond. Dexamethasone is taken by mouth at 20 milligrams or 40 milligrams on days 1, 8, 15 and 22. Treatment continues until the disease progresses or side effects become unacceptable.

The application was reviewed under Project Orbis, an initiative of the FDA Oncology Center of Excellence that allows oncology drugs to be submitted and reviewed at the same time by international partners. For this review, the FDA worked with Switzerland's Swissmedic. The application was granted priority review, and Zenbexus previously received breakthrough therapy and orphan drug designations.

What Are the Side Effects of Zenbexus for Multiple Myeloma?

The prescribing information for Zenbexus includes a boxed warning, the FDA's strongest type of warning, for embryo-fetal toxicity and for serious venous and arterial thromboembolism, which refers to blood clots in the veins and arteries.

The prescribing information also includes warnings and precautions for neutropenia, a drop in a type of white blood cell that helps fight infection, as well as for infections and for secondary primary malignancies, meaning new cancers that develop after treatment.

Because of the risk of embryo-fetal toxicity, Zenbexus is available only through a restricted distribution program called the ZENBEXUS Risk Evaluation and Mitigation Strategy, or REMS.

Health care professionals are asked to report all serious side effects suspected to be associated with the use of any medicine or device to the FDA's MedWatch Reporting System or by calling 1-800-FDA-1088.

References

1. "FDA grants accelerated approval to iberdomide with daratumumab and hyaluronidase-fihj and dexamethasone for multiple myeloma" News Release. U.S. Food and Drug Administration, Aug. 13, 2026.

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