Iberdomide - a CELMoD

What Is Iberdomide?

Iberdomide is a CELMoD agent that is being studied in many clinical trials with different drug combinations and in different myeloma patient populations.

As of August 13, 2026, the FDA granted accelerated approval to ZENBEXUS™ (iberdomide) in combination with Darzalex Faspro®( daratumumab and hyaluronidase-fihj) and dexamethasone (ZDd) for the treatment of adult patients with multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent.

What Are CELMoDs?

Cereblon (CRBN) E3 ligase modulators (CELMoDs) are a new drug class in myeloma. The emergence of CELMoDs is building on the well-established platform of immunomodulatory agents. CELMoDs are oral (taken by mouth) medications that have many similarities to immunomodulatory agents. Yet, CELMoDs can be used even in patients who have relapsed after treatment with immunomodulatory agents.

How Is Iberdomide Administered?

Iberdomide is taken by mouth. It can be combined with other myeloma therapies, such as proteasome inhibitors and monoclonal antibodies.

How Is Iberdomide Used in Multiple Myeloma?

On Thursday, August 13, 2026, the Food and Drug Administration (FDA) granted accelerated approval to Zenbexus (iberdomide), in combination with Darzalex Faspro (daratumumab and hyaluronidase-fihj) and dexamethasone as treatment for adults with relapsed/refractory myeloma (RRMM) who have received at least one prior line of therapy — including a proteasome inhibitor and an immunomodulatory agent. 

The approval was based on efficacy results from EXCALIBER-RRMM (NCT04975997), a two-stage, randomized, multicenter, open-label trial in adults with RRMM who had previously received one or two lines of therapy. Patients whose disease was refractory to prior anti-CD38 monoclonal antibody therapy or prior bortezomib were excluded.

2026 NCCN Guidelines and Zenbexus  

The September 2026 NCCN updated Clinical Practice Guidelines in Oncology: Multiple Myeloma recommend Darzalex (daratumumab, Zenbexus™ (iberdomide), and dexamethasone (Category 1) as "Other Recommended Options.” Note: The updated NCCN recommendations represent guidance for clinicians. Treatment decisions remain dependent on a patient’s disease characteristics, treatment history, and clinical circumstances. 

Some history of iberdomide in clinical trials

Previously in clinical trials, iberdomide demonstrated some positive results. For example, combination therapy with iberdomide and dexamethasone (also called “IBER-dex”) has shown an overall response rate (ORR) of about 30% to 50% in patients with heavily pretreated myeloma. These heavily pretreated patients have undergone 4 to 6 median prior therapies. These patients were triple-class refractory to proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies.

In December 2023, the first results of the phase II clinical trial EMN26 of iberdomide maintenance therapy to prolong remission after autologous stem cell transplantation (ASCT) in newly diagnosed patients with myeloma demonstrated a favorable safety profile and response improvement at 6 months when compared to maintenance therapy with Revlimid. 

Induction therapy with proteasome inhibitor Kyprolis® (carfilzomib), iberdomide, and the steroid dexamethasone (KID) appears safe and did not interfere with stem cell mobilization in a phase I/II clinical trial of ASCT-eligible patients with newly diagnosed multiple myeloma (NDMM). 

In May 2024, the Journal of Clinical Oncology published the results of the phase II clinical trial I2D by the Intergroupe Francophone du Myélome (IFM), a cooperative myeloma research group that is composed of 140 medical centers in France and 33 centers in Belgium. The I2D study evaluated the all-oral “triplet” (3-drug) study regimen of iberdomide, the proteasome inhibitor Ninlaro® (ixazomib), and dexamethasone in elderly patients with myeloma at first relapse.

The I2D study demonstrated a favorable efficacy and safety profile, including in patients with myeloma who were refractory to Revlimid and to the monoclonal antibody Darzalex® (daratumumab). The ORR was 65%, including 36% of study patients who achieved either complete response (CR) or very good partial response (VGPR). With a median follow-up of 14 months, the 12-month overall survival (OS) was 86%, the 12-month duration of response (DoR) was 76%, and the 12-month progression-free survival (PFS) was 52%.

Published in The Lancet Oncology in September 2026, the EXCALIBUR-RRMM study compared “iberdomide, daratumumab, and dexamethasone with daratumumab, bortezomib, and dexamethasone.”  It used “minimal residual disease (MRD)-negative complete response (CR) and progression-free survival (PFS) as dual primary endpoints.” The study showed ibedromide, daratumumab, and dexamethasone (IberDd) had significantly improved MRD-negative CR versus DVd (41.1% vs 20.7%).” 

The benefit was seen across prespecified subgroups, including in patients with prior lenalidomide exposure, refractoriness, and when lenalidomide was used in the last line of treatment. Evaluation of the PFS (dual) primary endpoint is ongoing.

IberDd demonstrated that the safety profile was consistent with the known effects of CELMoDs and daratumumab and dexamethasone (Dd). The most common side effect was neutropenia, which was mostly manageable with granulocyte-colony-stimulating factors (G-CSF) and dose interruptions. Most infections were grade 3 or lower and manageable with standard clinical practice and supportive care.  

What Are Potential Side Effects of Iberdomide?

A side effect, also called an adverse event (AE), is an unwanted or unexpected effect caused by a drug. Key risks of iberdomide include the following:

• Low blood counts (especially neutrophils). This increases the risk of infection.
• Blood clots. Patients taking iberdomide should be given medication to prevent blood clots.

Patients may also experience low-grade fatigue and diarrhea. Yet diarrhea appears to be less frequent with iberdomide than with lenalidomide. The risk of peripheral neuropathy and cardiac complications is low. 

Iberdomide is associated with Grade 3 infection and anemia, and Grade 3 or 4 neutropenia.