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FDA approves iberdomide for the treatment of patients with R/R multiple myeloma

On August 13, 2026, the U.S. Food and Drug Administration (FDA) granted approval to iberdomide combined with daratumumab and hyaluronidase-fihj and dexamethasone for the treatment of patients with relapsed/refractory (R/R) multiple myeloma who have received one or more prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.1

Multiple myeloma is a hematological malignancy characterized by the uncontrolled proliferation of clonal plasma cells and a relapsing-remitting disease course.2 Although recent therapeutic advances have improved patient outcomes, the high rate of relapse and progressive shortening of treatment-free intervals with successive lines of therapy highlight the need for novel therapies capable of achieving deep and durable responses in later lines of treatment.2

Iberdomide belongs to a next-generation class of agents known as cereblon E3 ligase modulators (CELMoDs).2 Similarly to well-established immunomodulatory drugs (IMiDs), such as lenalidomide and pomalidomide, CELMoDs bind to cereblon within the E3 ubiquitin ligase complex, promoting the degradation of the transcription factors IKZF1 and IKZF3, which are essential for myeloma cell survival. However, CELMoDs bind cereblon with 20-fold greater affinity than IMiDs, translating into enhanced anti-myeloma activity and immunomodulatory effects. Iberdomide has also demonstrated in vitro synergy with standard-of-care myeloma agents, such as daratumumab and dexamethasone, and can potentially overcome the IMiD resistance often observed in R/R disease.2

The FDA approval of iberdomide is based on results from a planned interim analysis of the measurable residual disease (MRD) endpoint from the ongoing multicenter, two-stage, randomized, open-label Phase III EXCALIBER-RRMM trial (NCT04975997) that enrolled patients with R/R multiple myeloma who received 1–2 prior lines of therapy.2 In stage 1 of the trial, 279 patients were randomized to one of three dose levels of iberdomide in combination with daratumumab and hyaluronidase-fihj and dexamethasone (IberDd) or to standard-of-care daratumumab and hyaluronidase-fihj, bortezomib and dexamethasone (DVd). 1 In stage 1, an iberdomide dose of 1.0 mg was confirmed as the optimal dose and this was taken forward into stage 2, in which 660 patients were randomized to IberDd or DVd.1

The primary efficacy population group included the first 420 patients randomized to receive IberDd (n=207) or DVd (n=213) across stages 1 and 2.1 The main efficacy outcome was MRD-negative complete response (CR) at any time, which was achieved by a significantly greater proportion of patients in the IberDd arm (41%; 95% CI: 34–48), compared with the DVd arm (21%; 95% CI: 15–27; p<0.0001).1

Advances in MRD detection methods, including next-generation sequencing and flow cytometry, have established MRD assessment as a precise means of quantifying disease burden and, consequently, MRD negativity is increasingly being recognized as a potential surrogate measure for PFS, supporting regulatory decisions and enabling this FDA approval of iberdomide based on interim MRD data.2, 3

In a recent interview at the 31st Congress of the European Hematology Association (EHA 2026), Fredrik Schjesvold, MD, PhD, Oslo University Hospital, Oslo, Norway, discussed the promise of CELMoDs, stating that, “I think it’s an exciting year for the CELMoDs. We have had lenalidomide and pomalidomide the IMiDs, for many years, but now we have more efficacious products with iberdomide and mezigdomide…”.

The approval of iberdomide marks the introduction of the first CELMoD into the myeloma treatment landscape, expanding second-line options with an effective, well-tolerated therapy with the potential to induce deep and durable responses in combination with standard of care agents in patients with R/R disease.1

References

  1. U.S. Food and Drug Administration. FDA grants accelerated approval to iberdomide with daratumumab and hyaluronidase-fihj and dexamethasone for multiple myeloma. Available here. (Last Accessed 13/08/2026).
  2. Lonial S, Dimopoulos MA, Berdeja JG, et al. EXCALIBER-RRMM: a phase III trial of iberdomide, daratumumab, and dexamethasone in relapsed/refractory multiple myeloma. Future Oncol. 2025;21(14):1761-1769.
  3. Bristol Myers Squibb. 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. Available here. (Last Accessed 14/08/2026).

Written by Clare Harris

Edited by Natalie Markova