Dr Banerjee on the FDA Approval of Iberdomide Plus Daratumumab/Dexamethasone in R/R Myeloma

IberDd is a BCMA-sparing regimen. You can save BCMA [targeting] for later down the line, or maybe use it after BCMA. Importantly, it works so much better in my mind than [daratumumab, pomalidomide, and dexamethasone]. Comparing them both mechanistically and [by] the study results, IberDd is the way to go.

Rahul Banerjee, MD, FACP, an associate professor in the Clinical Research Division at Fred Hutchinson Cancer Center and an associate professor in the Division of Hematology and Oncology at the University of Washington School of Medicine, discussed the FDA accelerated approval of iberdomide (Zenbexus) in combination with daratumumab and hyaluronidase-fihj (Darzalex Faspro) plus dexamethasone (IberDd) for adult patients with multiple myeloma who have received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent.

On August 13, 2026, the FDA granted accelerated approval to the regimen based on findings from the 2-stage, randomized, multicenter, open-label phase 3 EXCALIBER-RRMM trial (NCT04975997). In the primary efficacy population of the first 420 patients randomly assigned, IberDd (n = 207) generated a minimal residual disease (MRD)–negative complete response rate at any time of 41% (95% CI, 34%-48%) vs 21% (95% CI, 15%-27%) with daratumumab, pomalidomide (Pomalyst), and dexamethasone (DVd; n = 213; P < .0001).

CELMoDs represent a mechanistically distinct class from immunomodulatory drugs (IMiDs) such as lenalidomide (Revlimid) and pomalidomide, Banerjee emphasized. Although both classes act on Ikaros and Aiolos in myeloma cells, the CELMoDs drive more potent degradation of those proteins and, more importantly, activate T cells far more effectively than would otherwise be expected, he explained. According to Banerjee, these agents behave so differently from IMiDs that a patient’s status as CELMoD-refractory vs IMiD-refractory should be considered distinct, and IberDd offers a compelling option for patients who are lenalidomide-refractory.

A key advantage of IberDd is that it is BCMA-sparing, allowing for the preservation of BCMA-directed options for later lines or to deploy the regimen after BCMA-targeted therapy, Banerjee said. He framed IberDd as particularly valuable for patients who do not want bispecific antibodies or CAR T-cell therapy in earlier lines of therapy, who are wary of the associated toxicities with those classes of therapy, or who are treated at centers that cannot deliver those therapies. For patients who are candidates for and want CAR T-cell therapy or a bispecific antibody, Banerjee said he would still lean toward those approaches; however, for patients for whom they are not the right fit, he concluded that IberDd is an impressive and welcome addition to the relapsed/refractory armamentarium.