Iberdomide Offers Multiple Clinical and Strategic Roles in Relapsed Myeloma

Surbhi Sidana, MD, associate professor of medicine at Stanford University and chair of the American Society of Hematology (ASH) Committee on Communication, discusses the practice-changing impact of the regulatory approval of the iberdomide (Zenbexus), daratumumab (Darzalex), and dexamethasone (Iber-Dd) regimen in relapsed/refractory multiple myeloma (R/R MM). Beyond introducing a novel therapeutic combination, this milestone represents a trailblazing precedent for the myeloma field, as it marks the first regulatory approval granted based on measurable residual disease (MRD) end points.

The approval of iberdomide, a novel cereblon E3 ligase modulator (CELMoD), expands an increasingly diverse therapeutic landscape in early relapse. Although academic centers frequently prioritize advanced T-cell redirecting immunotherapies, such as chimeric antigen receptor (CAR) T-cell therapy or bispecific antibodies, iberdomide provides a highly effective, oral alternative. Because the majority of patients with myeloma receive care in community practices, an oral CELMoD-based regimen drastically reduces treatment burden and travel frequency compared to infusion-heavy platforms, democratizing access to modern therapies outside specialized academic institutions.

Beyond its role as a standalone, community-accessible regimen, Sidana points out that iberdomide offers versatile complementary utility alongside advanced immunotherapies: the Iber-Dd regimen can provide an effective, outpatient option to maintain disease control locally while patients await CAR T-cell manufacturing and infusion. Because iberdomide can help address T-cell exhaustion, it could also be used following bispecific antibody treatment, acting as an intermediate therapeutic bridge to optimize immune fitness prior to subsequent T-cell redirecting approaches. It also synergizes with CAR T-cell platforms in high-risk early relapsed disease, and there are ongoing trials evaluating CELMoD maintenance to enhance and sustain T-cell activity after infusion.

By combining community accessibility with high-level academic strategy, the integration of iberdomide into early-relapse protocols provides a versatile, oral foundation that enhances treatment personalization, complements cellular therapies, and can improve outcomes regardless of whether a patient is a preferred candidate for high-intensity therapies.