Unraveling the Potential of Iberdomide and CELMoDs in Multiple Myeloma

In a conversation with CancerNetwork^®, Sagar Lonial, MD, FACP, FASCO, discussed the potential implications of the FDA approving iberdomide plus daratumumab (Darzalex) and dexamethasone for patients with relapsed/refractory multiple myeloma. He spoke in context of the FDA accepting a new drug application for the iberdomide regimen based on data from the phase 3 EXCALIBER-RRMM trial (NCT04975997).¹

Lonial discussed the potential benefits that iberdomide could offer based on its properties as a CELMoD. He noted how the potency, safety profile, and targeting capabilities of this drug class may differentiate it from previous standards such as immunomodulatory drugs.

Regarding the supporting findings from the EXCALIBER-RRMM trial, Lonial stated that the study was the “first test case” for using minimal residual disease (MRD) as an early end point for approval. In September 2025, investigators announced that iberdomide-based therapy showed a significant improvement in MRD-negative status vs daratumumab, bortezomib (Velcade), and dexamethasone.²

The potential approval of iberdomide in this multiple myeloma population, Lonial said, would open the door for using the agent in combination with other immunotherapies. Noting that T-cell engagers are “perfect partners” for the CELMoD class, Lonial emphasized the utility of combination regimens across the field.

“Recognizing that we have agents that can reset or augment immunity and partnering them [are important]. People always want to say it's a black and white world; you're either going to use this, or you're going to use this. To me, it's about combination therapy,” Lonial stated. “Having this tool belt with many drugs and putting them together in combinations is how we get to [a] cure.”

Lonial is a professor and chair of the Department of Hematology and Medical Oncology and the Anne and Bernard Gray Family Chair in Cancer at Emory University School of Medicine, and the chief medical officer at Winship Cancer Institute of Emory University. He is also a member of the International Myeloma Foundation scientific board.

References

1. U.S. Food and Drug Administration accepts Bristol Myers Squibb's new drug application for iberdomide in patients with relapsed or refractory multiple myeloma. News release. Bristol Myers Squibb. February 17, 2026. Accessed March 5, 2026. https://tinyurl.com/4c8mb6ex
2. Bristol Myers Squibb announces phase 3 EXCALIBER-RRMM study evaluating iberdomide in combination with standard therapies demonstrated a significant improvement in minimal residual disease negativity rates in relapsed or refractory multiple myeloma. News release. Bristol Myers Squibb. September 23, 2025. Accessed March 5, 2026. https://tinyurl.com/5n9768k5