Potential Iberdomide Approval May Offer Another Choice in Multiple Myeloma

In February 2026, the FDA accepted a new drug application (NDA) seeking approval for iberdomide, a cereblon E3 ligase modulator (CELMoD) agent, in combination with daratumumab (Darzalex) and dexamethasone for patients with released/refractory multiple myeloma.¹ In light of this regulatory milestone, Sagar Lonial, MD, FACP, FASCO, spoke with CancerNetwork^® about the potential clinical implications if the FDA were to approve the iberdomide-based combination.

Although the early relapse therapy setting is a “very crowded space” in multiple myeloma space, Lonial noted that the availability of the iberdomide combination would offer an additional choice to patients alongside regimens like teclistamab-cqyv (Tecvayli) plus daratumumab, which was evaluated in the phase 3 MajesTEC-3 trial (NCT05083169).² Additionally, the fact that the novel regimen partly incorporates an oral therapeutic component would be “favorable” in terms of offering convenience to patients.

Lonial also highlighted other combination strategies that show potential in the multiple myeloma space based on data presented at the 2025 American Society of Hematology Annual Meeting & Exposition (ASH). These regimens include iberdomide plus elranatamab-bcmm (Elrexfio) in the phase 1b MagnetisMM-30 trial (NCT04649359) as well as mezigdomide plus elranatamab in the phase 1 MELT-MM trial (NCT06645678).^3,4

Lonial is a professor and chair of the Department of Hematology and Medical Oncology at Emory University School of Medicine and the chief medical officer at Winship Cancer Institute of Emory University.

Transcript:

When we think about [iberdomide plus daratumumab/dexamethasone] in the early relapse therapy setting, as we know, it is a very crowded space. To me, what it does is offer patients choices. We certainly know that CAR T-cell data in this space looks good. We also know from MajesTEC-3 that teclistamab and [daratumumab] also looks good in this space. But [not all] patients have access to all those treatments, necessarily. Having a highly effective treatment, particularly one that uses—at least in part—an oral approach, is certainly very favorable from a patient convenience perspective.

To me, this [potential approval] opens the door of using iberdomide with other immune agents. At ASH [in 2025], we saw iberdomide in combination with elranatamab in the [MagnetisMM-30] trial. We also saw mezigdomide, the other CELMoD, in combination with elranatamab in the MELT-MM study. These are perfect partners—the T-cell engagers—for the CELMoD class as potentially used either before collection of T cells for a CAR or as short-duration maintenance after a CAR as well. It’s opening the field for these agents down the road.

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 February 26, 2026. https://tinyurl.com/4c8mb6ex
2. Costa LJ, Bahlis NJ, Perrot A, et al. Teclistamab plus daratumumab in relapsed or refractory multiple myeloma. N Engl J Med. 2026;394(8):739-752. doi:10.1056/NEJMoa2514663
3. Suvannasankha A, Kaufman J, Badros A, et al. Safety and efficacy of elranatamab in combination with iberdomide in patients with relapsed or refractory multiple myeloma: results from the phase 1b MagnetisMM-30 trial. Blood. 2025;146(suppl 1):100. doi:10.1182/blood-2025-100
4. Byun JM, Min C-K, Kim K, et al. Phase I/II study of mezigdomide and elranatamab for relapsed/refractory multiple myeloma patients (MELT-MM): initial results from part 1. Blood. 2025;146(suppl 1):5835. doi:10.1182/blood-2025-5835