The FDA has approved iberdomide (Zenbexus, Bristol Myers Squibb) in combination with daratumumab and dexamethasone for relapsed or refractory multiple myeloma (RRMM).

The approval was based on the phase 3 EXCALIBER-RRMM trial, a two-stage, randomized, multicenter, open-label trial in adults with RRMM who had previously received one or two prior lines of therapy. Patients were excluded if they had a disease that was refractory to prior anti-CD38 monoclonal antibody therapy or to prior bortezomib, according to a statement from the FDA on the accelerated approval.

Iberdomide is a first-in-class cereblon E3 ligase modulator, a next-generation immunomodulatory drug (IMiD) that helps eliminate proteins that myeloma cells need to survive. It is designed to be a more potent version of older IMiDs such as lenalidomide and pomalidomide.

EXCALIBER-RRMM Trial Results

Approximately 200 patients were randomly assigned 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. In stage 2 of EXCALIBER-RRMM, 664 patients were evenly and randomly assigned to IberDd or DVd, which is a standard option for previously treated disease.

The primary efficacy population included the first 420 patients randomly assigned to iberdomide 1 mg in combination with daratumumab and dexamethasone (n = 207) or the comparator DVd arm (n = 213) across stage 1 and stage 2 of the trial. The minimal residual disease-negative complete response rate at any time was 41% in the IberDd arm and 21% in the DVd arm (P < .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.

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, until disease progression or unacceptable toxicity.

M. Alexander Otto is a physician assistant and award-winning journalist. He is also an MIT science journalism fellow. Email: aotto@medscape.net.