Iberdomide and the Rise of CELMoDs in Multiple Myeloma

The landscape of relapsed or refractory multiple myeloma (RRMM) treatment is shifting toward a more targeted future. Recently, the U.S. Food and Drug Administration (FDA) accepted a new drug application (NDA) for iberdomide, a first-in-class cereblon E3 ligase modulator (CELMoD). When combined with Darzalex (daratumumab) and dexamethasone (IberDd), this oral therapy offers a potent potential new strategy for patients who have exhausted traditional options.

This milestone is particularly significant as it marks the transition from the well-known immunomodulatory drugs (IMiDs) — like Revlimid (lenalidomide) and Pomalyst (pomalidomide) — to the next generation of "protein degraders." To help patients understand the clinical impact of this shift, CURE spoke with Dr. Sagar Lonial, Professor and Chair of the Department of Hematology and Medical Oncology at Emory University School of Medicine.

Lonial explained how iberdomide’s unique "bind-and-kill" mechanism differs from its predecessors and why this "evolution" in treatment could provide deeper, more durable remissions for the myeloma community.

Transcript

The FDA’s acceptance of this NDA marks a potential first for a new class of drugs called CELMoDs. For patients who are already familiar with IMiDs like Revlimid or Pomalyst, how would you explain the fundamental difference in how iberdomide works, and why should they be excited about this new "evolution" of treatment?

The way that I think about it is that [Revlimid] and [Pomalyst] are sort of from an older class called the IMiDs. What really distinguishes the CELMoDs — which include iberdomide, or "iber" for short, and mezigdomide — is that they were engineered to be more effective at targeting the immune system.

We know that the IMiD class does have a pro-immune system effect; it makes immune therapies more effective. However, the CELMoDs are like doing that on steroids. They do it far more effectively than the previous classes. At the same time, because their binding affinity is so much tighter than what we saw with the IMiD class, they behave differently. Unlike [Revlimid] and [Pomalyst], which really just arrest cell growth, the CELMoDs actually kill the cells. They are actually cytotoxic. That differentiation is a consequence of potency, and it simply makes these drugs more effective.

Transcript has been edited for clarity and conciseness.

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