FDA grants accelerated approval to iberdomide with daratumumab and hyaluronidase-fihj and dexamethasone for multiple myeloma

On August 13, 2026, the Food and Drug Administration granted accelerated approval to iberdomide (Zenbexus, Bristol-Myers Squibb Company) 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.

Full prescribing information for Zenbexus will be posted on Drugs@FDA.

Efficacy and Safety

Efficacy was evaluated in EXCALIBER-RRMM (NCT04975997), a two-stage, randomized, multicenter, open-label trial in adults with relapsed or refractory multiple myeloma (RRMM) who had previously received one or two prior lines of therapy. Patients who had disease refractory to prior anti-CD38 monoclonal antibody therapy, or to prior bortezomib were excluded.

A total of 939 patients were randomized to one of three dose levels of iberdomide in combination with daratumumab and hyaluronidase-fihj and dexamethasone (IberDd) or to daratumumab and hyaluronidase-fihj, bortezomib and dexamethasone (DVd) in stage 1 (n=279); or to iberdomide 1 mg in combination with daratumumab and hyaluronidase-fihj and dexamethasone (Dd) or DVd in stage 2 (n=660).

The major efficacy outcome measure was minimal residual disease (MRD)-negative complete response (CR) at any time. The primary efficacy population included the first 420 patients randomized to iberdomide 1 mg in combination with Dd (n=207) or the comparator DVd arm (n=213) across stages 1 and stage 2. The MRD- negative CR rate at any time was 41% (95% CI: 34, 48) in the IberDd arm and 21% (95% CI: 15, 27) in the DVd arm (p-value <0.0001).

The prescribing information includes a boxed warning for embryo-fetal toxicity and serious venous and arterial thromboembolism, as well as warnings and precautions for neutropenia, infections, and secondary primary malignancies. Because of the risk of embryo-fetal toxicity, iberdomide is available only through a restricted distribution program called ZENBEXUS Risk Evaluation and Mitigation Strategy (REMS).

Recommended Dosage

The recommended iberdomide dosage is 1 mg orally once daily, with or without food, on Days 1 through 21 of a 28-day cycle, in combination with daratumumab and hyaluronidase-fihj and dexamethasone. Daratumumab and hyaluronidase-fihj is administered subcutaneously at 1800 mg on Days 1, 8, 15, and 22 of Cycles 1–2; Days 1 and 15 of Cycles 3–6; and Day 1 of Cycles 7 and beyond. Dexamethasone is administered orally at 20 mg or 40 mg on Days 1, 8, 15, and 22. Treatment should continue until disease progression or unacceptable toxicity.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with Switzerland’s Swissmedic.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted priority review. Iberdomide also received breakthrough therapy and orphan drug designations. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.