Iberdomide Complements CAR T in Myeloma: Swarup Kimar, MD

The FDA’s August 13 accelerated approval of iberdomide plus daratumumab and dexamethasone (IberDd; Zenbexus; Bristol Myers Squibb) for relapsed/refractory multiple myeloma (MM) gives clinicians a new oral options, but it won’t replace chimeric antigen receptor (CAR) T-cell therapy or bispecific antibodies for high-risk patients, according to Swarup Kumar, MD, assistant clinical professor of medicine at UConn Health’s Neag Comprehensive Cancer Center and leader of its multiple myeloma and plasma cell disorders program.

Kumar said he would still favor CAR T-cell therapy or bispecific therapy for fit, high-risk patients in the second-line setting, given the maturity of data on depth and durability of response with those approaches. But he also sees a clear role for iberdomide among patients without ready access to a CAR T-cell therapy center, those in settings with limited bispecific experience, or frail patients who need a less-intensive oral regimen. Notably, the drug appears to retain activity in patients previously exposed to lenalidomide of pomalidomide, a population that has historically had few options.

That activity was reflected in the phase 3 EXCALIBER-RRMM trial (NCT04975997), which showed a 41% minimal residual disease (MRD)-negative complete response rate with IberDd. Kumar called the signal impressive but cautioned that the durability of the MRD-negative response, not the rate itself, will determine its long-term significance for progression-free and overall survival.

Because iberdomide carries risks of cytopenias, infections, and thromboembolic events, Kumar emphasized that patients need a structured pretreatment plan under the drug’s REMS program, including early granulocyte colony-stimulating factor support for neutropenia, infection prophylaxis, and thromboprophylaxis. He said iberdomide’s future may extend beyond its daratumumab pairing, pointing to ongoing studies combining it with T-cell-engager therapies to improve depth of response, including in the post–CAR T-cell therapy setting.

“I think that there is always going to be a population that’s going to derive benefit from this,” he emphasized, “and I think it’s important to be prepared.”