Iberdomide combination improves MRD–negative complete response rates versus DVd in relapsed or refractory multiple myeloma

The combination of iberdomide, a novel cereblon E3 ligase modulator, with daratumumab and dexamethasone improved rates of minimal residual disease–negative complete response compared with daratumumab, bortezomib, and dexamethasone (DVd) for patients with relapsed or refractory multiple myeloma, according to authors of the EXCALIBER-RRMM study.

Data from the phase 3 trial, led by Sagar Lonial, MD, of Winship Cancer Institute of Emory University in Atlanta, Georgia, were published in The Lancet Oncology.

EXCALIBER-RRMM enrolled patients with relapsed or refractory multiple myeloma who had one or two previous lines of therapy, achieved a partial response, and then had disease progression. In stage 2 of the trial, researchers randomized 800 patients to either iberdomide, daratumumab, and dexamethasone or DVd. The primary MRD analysis encompassed an intention-to-treat population of 207 patients in the iberdomide arm and 213 in the DVd arm.

After a median follow-up of 15.7 months (interquartile range, 12.8-23.2), 41% of patients in the iberdomide arm achieved MRD–negative complete response compared with 21% of the DVd arm (stratified proportion difference, 20.1%; 95% CI, 11.5-28.6; P<.0001; odds ratio, 2.8; 95% CI, 1.8-4.3). Progression-free survival analysis is ongoing.

Grade 3 or 4 adverse events (AEs) occurred in 92% of the iberdomide arm and 70% of the DVd arm, including neutropenia in 84% versus 11% and infection in 39% versus 22%, respectively. Serious AEs occurred in 58% of the iberdomide arm and 41% of the DVd arm, the most common of which was pneumonia in 18% versus 6%, respectively. Three deaths in the iberdomide arm and two in the DVd arm were judged related to any study treatment.

“These findings support iberdomide, daratumumab, and dexamethasone as an efficacious treatment option for patients with relapsed or refractory multiple myeloma with the potential to be administered across diverse care settings,” Dr. Lonial and colleagues wrote.

Reference
Lonial S, Dimopoulos MA, Gavriatopoulou M, et al. Iberdomide plus daratumumab and dexamethasone versus daratumumab, bortezomib, and dexamethasone in patients with relapsed or refractory multiple myeloma (EXCALIBER-RRMM): an open-label, randomised, controlled, phase 3 trial. The Lancet Oncology Published online September 2026. doi:10.1016/s1470-2045(26)00450-x