Iberdomide (Zenbexus, CC-220) for Multiple Myeloma: FDA-Approved August 2026 — First-in-Class CELMoD, Plus 14 Recruiting Trials Across Smoldering, Newly Diagnosed, Post-ASCT Maintenance, and Relapsed/Refractory Disease

Last updated: August 16, 2026

✅ Regulatory status — FDA-approved August 13, 2026 (accelerated): The FDA granted accelerated approval to iberdomide (brand name Zenbexus, Bristol Myers Squibb) in combination with daratumumab and hyaluronidase-fihj and dexamethasone (ZDd) for adults with multiple myeloma who have had at least one prior line of therapy (as early as first relapse) — the first CELMoD ever approved. Approval was based on the Phase 3 EXCALIBER-RRMM trial (ZDd vs DVd), with a significantly higher MRD-negative complete response rate (41% vs 21%, p<0.0001). Because of embryo-fetal toxicity, Zenbexus is available only through a REMS program. Note: iberdomide is not yet approved in the earlier-disease settings (smoldering, newly diagnosed, post-transplant maintenance) that the recruiting trials below are still studying. Always confirm the current FDA prescribing information.

📌 Why this page exists: Iberdomide (CC-220) is the lead next-generation CELMoD — the successor class to lenalidomide (Revlimid) and pomalidomide (Pomalyst) — and in August 2026 became the first CELMoD to win FDA approval (as Zenbexus, for relapsed/refractory MM). Because it retains activity in some IMiD-resistant disease and stimulates the immune system, it is being tested across the entire myeloma spectrum: from high-risk smoldering myeloma (before active disease), through newly diagnosed MM and post-transplant maintenance, to relapsed/refractory combinations with antibodies and bispecifics. For the full multiple myeloma landscape, see our multiple myeloma trials page.

About Iberdomide (CC-220)

Drug profile:

Iberdomide (code CC-220; brand name Zenbexus, FDA-approved August 2026) is an oral cereblon E3 ligase modulator (CELMoD) developed by Bristol Myers Squibb. It is the next generation of the same cereblon-targeting mechanism used by the immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide — but engineered to bind cereblon more tightly and degrade its targets more potently.

How it works:

Iberdomide co-opts the cereblon (CRBN) E3 ubiquitin ligase to tag the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) — proteins that myeloma cells depend on for survival — for destruction by the proteasome. Compared with lenalidomide and pomalidomide, iberdomide drives faster and more complete degradation of these targets. This produces a dual effect: a direct anti-myeloma (tumor-killing) action, and an immunostimulatory action that activates T cells and NK cells. Because the binding is more potent, iberdomide can retain activity in some myeloma that has already become resistant to lenalidomide or pomalidomide.

Regulatory status:

FDA-approved August 13, 2026 (accelerated approval). Iberdomide (Zenbexus) in combination with daratumumab and hyaluronidase-fihj and dexamethasone (ZDd) for multiple myeloma after at least one prior line of therapy — the first-in-class CELMoD approved. It had held Breakthrough Therapy Designation and Priority Review; approval came a few days ahead of the August 17, 2026 PDUFA date.
Registrational trial: Phase 3 EXCALIBER-RRMM, which compared ZDd against daratumumab + bortezomib + dexamethasone (DVd) and showed a significantly higher rate of MRD-negative complete response (41% vs 21%, p<0.0001) at ~16 months of follow-up. (Completed enrollment; not among the recruiting trials below.)
Availability: Zenbexus is now commercially available for the approved RRMM (ZDd) indication through the REMS program. For the earlier settings still under study (smoldering, newly diagnosed, maintenance), access remains through the clinical trials listed below.

IMiD → CELMoD: why the next generation matters

Lenalidomide and pomalidomide (the IMiDs) are among the most important drugs in myeloma — used in induction, maintenance, and relapse. But nearly all patients eventually become IMiD-refractory, and lenalidomide maintenance is now so widespread that many patients relapse already resistant to it. CELMoDs were designed for exactly this problem: by binding cereblon more avidly and degrading Ikaros/Aiolos more completely, iberdomide (and its sibling mezigdomide) can work where the older IMiDs no longer do, and pair naturally with the antibodies and bispecifics that now dominate myeloma care. That is why the recruiting portfolio below spans the whole disease course — the field is testing whether the next-generation cereblon backbone can replace lenalidomide/pomalidomide from smoldering disease all the way through late relapse.

Active Research Directions in 2026

The approved RRMM regimen (ZDd) — iberdomide + daratumumab/hyaluronidase-fihj + dexamethasone, FDA-approved August 13, 2026 on Phase 3 EXCALIBER-RRMM — the first CELMoD to reach the market, establishing iberdomide as a backbone partner for anti-CD38 antibodies as early as first relapse.
Moving into newly diagnosed disease (Phase 3) — NCT05558319 tests an iberdomide-containing induction (Isa-V-iberdomide) head-to-head against isatuximab-VRD and extended VRD in transplant-eligible newly diagnosed MM — a direct test of whether the CELMoD can improve on lenalidomide in front-line induction.
Replacing lenalidomide in post-ASCT maintenance (Phase 3) — NCT06216158 compares iberdomide vs iberdomide + isatuximab as maintenance after autologous stem cell transplant. Maintenance is lenalidomide's largest role in myeloma; this is where a next-generation CELMoD would displace the most standard-of-care use.
Early intervention in high-risk smoldering myeloma — NCT04776395 (iberdomide ± dexamethasone) and NCT06762769 (isatuximab + iberdomide + dexamethasone) test whether treating before active myeloma develops can delay or prevent progression — part of the broader 2026 shift toward intercepting high-risk smoldering disease.
CELMoD + bispecific combinations — iberdomide's immune-activating effect is a natural partner for T-cell–engaging bispecifics. Recruiting trials pair it with elranatamab (BCMA×CD3; MagnetisMM-30, NCT06215118), teclistamab (BCMA×CD3; NCT06465316), and talquetamab (GPRC5D×CD3; NCT06348108) — testing whether the CELMoD amplifies bispecific activity in relapsed disease.
CELMoD + antibody / ADC combinations — with anti-CD38 and anti-SLAMF7 antibodies and a BCMA ADC: Iber-KDd (NCT05896228), elotuzumab + daratumumab + iberdomide (NCT06785415), and iberdomide + belantamab mafodotin (NCT06232044).
Post-CAR-T sequencing — NCT06518551 tests elotuzumab + iberdomide after idecabtagene vicleucel (ide-cel) BCMA CAR-T — addressing what to give after CAR-T relapse.
Beyond myeloma (B-cell lymphoma) — NCT05169515 combines the CELMoDs CC-220 (iberdomide) and/or CC-99282 with the bispecifics mosunetuzumab or glofitamab in B-cell non-Hodgkin lymphoma — the main trial testing iberdomide's cereblon mechanism outside plasma-cell disease.

Recruiting Trials by Setting

High-Risk Smoldering Myeloma (Early Intervention) (2 trials)

NCT04776395 — Iberdomide ± Dexamethasone in Smoldering MM (Phase 2; Recruiting): Iberdomide alone or with dexamethasone in intermediate- or high-risk smoldering multiple myeloma — tests early single-agent CELMoD intervention before active disease.
NCT06762769 — Isatuximab + Iberdomide + Dexamethasone in Smoldering Myeloma (Phase 2; Recruiting): Anti-CD38 antibody plus the CELMoD plus dexamethasone in intermediate/high-risk smoldering myeloma — a more intensive immunotherapy approach to early intervention.

Newly Diagnosed Multiple Myeloma (2 trials)

NCT05558319 — Isa-V-Iberdomide vs Isa-VRD vs Extended VRD (Phase 3; Recruiting): A three-arm randomized Phase 3 in transplant-eligible newly diagnosed MM comparing an iberdomide-containing regimen (isatuximab + bortezomib + iberdomide) against isatuximab-VRD and extended VRD. Tests whether the CELMoD improves on lenalidomide in front-line induction.
NCT05272826 — Iberdomide + Bortezomib + Dexamethasone, Isatuximab on Demand (Phase 2; Recruiting): For newly diagnosed transplant-ineligible MM — iberdomide-bortezomib-dexamethasone with isatuximab added on demand based on response.

Post-Transplant Maintenance (2 trials)

NCT06216158 — Iberdomide vs Iberdomide + Isatuximab Maintenance Post-ASCT (Phase 3; Recruiting): Compares iberdomide-only vs iberdomide + isatuximab as maintenance after autologous stem cell transplant in newly diagnosed MM (the maintenance follow-on to the GMMG-HD8/DSMM XIX induction trial). The registrational-scale test of a CELMoD in myeloma's largest maintenance setting.
NCT06107738 — Iberdomide + Daratumumab Maintenance in MRD-Positive MM (Phase 2; Recruiting): For patients who remain minimal residual disease (MRD)-positive after initial therapy including ASCT — tests whether iberdomide + daratumumab maintenance can deepen response and convert to MRD-negativity.

Relapsed / Refractory MM — Antibody & ADC Combinations (3 trials)

NCT05896228 — Iber-KDd (Phase 2; Recruiting): Iberdomide + carfilzomib + daratumumab + dexamethasone in relapsed/refractory MM — a quadruplet pairing the CELMoD with a proteasome inhibitor and anti-CD38 antibody.
NCT06785415 — Elotuzumab + Daratumumab + Iberdomide + Dexamethasone (Phase 1/2; Recruiting): Dual-antibody (anti-SLAMF7 + anti-CD38) plus the CELMoD in relapsed MM.
NCT06232044 — Iberdomide + Belantamab Mafodotin + Dexamethasone (Phase 1/2; Recruiting): Pairs the CELMoD with the BCMA-directed antibody-drug conjugate belantamab mafodotin in relapsed/refractory MM.

Relapsed / Refractory MM — Bispecific & Post-CAR-T Combinations (4 trials)

Iberdomide's immune-activating effect makes it a natural partner for T-cell–engaging bispecifics:

NCT06215118 — MagnetisMM-30: Elranatamab + Iberdomide (Phase 1; Recruiting): The BCMA×CD3 bispecific elranatamab (Elrexfio) combined with iberdomide in relapsed/refractory MM.
NCT06465316 — Teclistamab (Tecvayli) + Iberdomide (Phase 1; Recruiting): The first-in-class BCMA×CD3 bispecific plus the CELMoD — tests whether next-generation cereblon modulation amplifies bispecific activity. (Also listed on our teclistamab page.)
NCT06348108 — Talquetamab + Iberdomide + Dexamethasone (Phase 1; Recruiting): The GPRC5D×CD3 bispecific (a non-BCMA target, useful after BCMA failure) plus the CELMoD in relapsed/refractory MM. (Also on our talquetamab page.)
NCT06518551 — Elotuzumab + Iberdomide Post Ide-Cel (Phase 1/2; Recruiting): Elotuzumab + iberdomide + dexamethasone after idecabtagene vicleucel (ide-cel) BCMA CAR-T — a post-CAR-T sequencing strategy.

B-Cell Non-Hodgkin Lymphoma (CELMoD Platform) (1 trial)

NCT05169515 — Mosunetuzumab or Glofitamab + CC-220 and/or CC-99282 in B-NHL (Phase 1; Recruiting): Combines the CELMoDs iberdomide (CC-220) and/or golcadomide (CC-99282) with the CD20×CD3 bispecifics mosunetuzumab or glofitamab — the main study extending iberdomide's cereblon mechanism beyond plasma-cell disease into B-cell lymphoma.

Showing all 14 recruiting interventional trials of iberdomide (CC-220) in the ClinTrialFinder corpus as of August 9, 2026. View the latest iberdomide search on ClinicalTrials.gov.

Trials Not Yet Recruiting

NCT07624513 — Determination 2 (Phase 3; Not Yet Recruiting): Isatuximab + iberdomide + bortezomib + dexamethasone induction in multiple myeloma — another Phase 3 testing an iberdomide-anchored quadruplet in the front-line setting.
NCT07601100 — Isa-Iber-VD in Transplant-Ineligible NDMM (Phase 1b/2; Not Yet Recruiting): Isatuximab + iberdomide + bortezomib + dexamethasone for newly diagnosed transplant-ineligible MM.
NCT07727668 — Iberdomide Priming Before CAR-T Leukapheresis (Phase 1; Not Yet Recruiting): Uses iberdomide (CC-220) to improve T-cell fitness before leukapheresis for CAR-T manufacturing in relapsed/refractory MM — a novel use of the CELMoD's immune-enhancing effect to make better CAR-T cells.
NCT07437963 — Iberdomide in Neuroblastoma (Phase 1/2; Not Yet Recruiting): Adds iberdomide to therapy in relapsed/refractory neuroblastoma — a pediatric solid-tumor extension of the cereblon-modulator mechanism. We list it for transparency; it is outside the multiple myeloma focus of this page.

Patient Selection and Practical Considerations

Approved for RRMM; investigational earlier. Iberdomide (Zenbexus, ZDd) is FDA-approved for multiple myeloma after at least one prior line of therapy. For the earlier settings above (smoldering, newly diagnosed, post-ASCT maintenance), it remains investigational — access there is by enrolling in one of these studies.
Prior lenalidomide/pomalidomide does not necessarily exclude you. Because iberdomide is a more potent cereblon modulator, many trials specifically enroll patients who have progressed on the older IMiDs — the CELMoD is being tested precisely for IMiD-refractory disease. Check each trial's criteria.
The combination partner shapes eligibility and risk. Iberdomide is almost always tested in combination. A bispecific partner (elranatamab, teclistamab, talquetamab) adds cytokine release syndrome and step-up-dosing considerations; an anti-CD38 partner (daratumumab, isatuximab) or the belantamab ADC brings its own profile. Match the trial to your prior exposures (anti-CD38, BCMA-directed therapy, CAR-T).
Disease stage matters for trial choice. Trials span smoldering myeloma, newly diagnosed (transplant-eligible and -ineligible), post-transplant maintenance (including MRD-positive), and relapsed/refractory disease — your stage and treatment history determine which are open to you.
Standard IMiD/CELMoD-class precautions apply — blood-clot prophylaxis and strict pregnancy-prevention requirements (the drug is teratogenic), as with lenalidomide and pomalidomide.

Side Effects (Iberdomide / CELMoD-Class Signals)

Iberdomide's safety profile reflects its cereblon-modulator class (shared with lenalidomide and pomalidomide), modified by whichever agent it is combined with. For the approved ZDd regimen, see the FDA-approved Zenbexus prescribing information; for the investigational earlier-setting combinations, the profile is still being characterized.

Cytopenias — neutropenia is the most common and dose-limiting effect (low white-cell counts, raising infection risk), along with anemia and thrombocytopenia. Managed with dose adjustment and growth-factor support.
Venous thromboembolism (blood clots) — a class effect of cereblon modulators; patients typically receive clot prophylaxis (aspirin or an anticoagulant).
Teratogenicity — like all cereblon modulators, iberdomide can cause severe birth defects; strict pregnancy-prevention requirements apply.
Infections — driven partly by neutropenia and partly by the combination partner; more pronounced when combined with a bispecific antibody or anti-CD38 agent.
Fatigue and gastrointestinal effects — fatigue, diarrhea or constipation, and rash can occur, as with other IMiD/CELMoD-class drugs.
Combination-specific effects — when paired with a T-cell–engaging bispecific (elranatamab, teclistamab, talquetamab), the regimen adds cytokine release syndrome (CRS) and the infection burden of that agent; these are properties of the partner, not of iberdomide itself.

Frequently Asked Questions

What is iberdomide (CC-220)?

Iberdomide (code CC-220) is an oral next-generation cereblon E3 ligase modulator (CELMoD) developed by Bristol Myers Squibb for multiple myeloma — the successor class to the IMiDs lenalidomide (Revlimid) and pomalidomide (Pomalyst). It binds cereblon more tightly and drives more potent degradation of the myeloma-survival transcription factors Ikaros (IKZF1) and Aiolos (IKZF3), producing both a direct tumor-killing effect and an immune-stimulating effect. On August 13, 2026 it received FDA accelerated approval as Zenbexus, with daratumumab/hyaluronidase-fihj + dexamethasone (ZDd), for multiple myeloma after at least one prior line — the first CELMoD approved, on the Phase 3 EXCALIBER-RRMM trial. It remains investigational in earlier settings (trials below).

Is iberdomide FDA-approved?

Yes, as of August 13, 2026 — the FDA granted accelerated approval to iberdomide (Zenbexus) with daratumumab/hyaluronidase-fihj + dexamethasone (ZDd) for multiple myeloma after at least one prior line of therapy, the first CELMoD approved (on the Phase 3 EXCALIBER-RRMM trial). It is dispensed through a REMS program. It is not yet approved for the earlier settings (smoldering, newly diagnosed, maintenance) still under study below. Always check the current FDA prescribing information for the latest status.

How is iberdomide different from lenalidomide and pomalidomide?

All three use the same cereblon mechanism — degrading Ikaros (IKZF1) and Aiolos (IKZF3) — but lenalidomide and pomalidomide are IMiDs and iberdomide is a CELMoD, the next generation. Iberdomide binds cereblon more tightly and degrades these targets more rapidly and completely, so it can retain activity in some myeloma that has become resistant to the older IMiDs, and it produces stronger immune activation. That is why it is being tested both in newly diagnosed disease (to build deeper responses) and after IMiD failure.

What iberdomide trials are currently recruiting?

There are 14 recruiting interventional iberdomide trials as of August 2026, spanning the full disease course. Smoldering myeloma: NCT04776395, NCT06762769. Newly diagnosed MM: NCT05558319 (Phase 3), NCT05272826. Post-ASCT maintenance: NCT06216158 (Phase 3), NCT06107738. Relapsed/refractory with antibodies/ADC: NCT05896228 (Iber-KDd), NCT06785415, NCT06232044 (+ belantamab mafodotin). Relapsed/refractory with bispecifics / post-CAR-T: NCT06215118 (elranatamab, MagnetisMM-30), NCT06465316 (teclistamab), NCT06348108 (talquetamab), NCT06518551 (post ide-cel). B-cell lymphoma: NCT05169515. Four more are not yet recruiting, including two front-line Phase 3 quadruplet trials and a novel iberdomide-priming study before CAR-T leukapheresis.

What are the main side effects of iberdomide?

As an oral cereblon modulator in the lenalidomide/pomalidomide family, iberdomide's most common effects are cytopenias — especially neutropenia (raising infection risk), plus anemia and thrombocytopenia. It carries the class risks of venous thromboembolism (blood clots), so clot prophylaxis is used, and teratogenicity (birth defects), so pregnancy-prevention requirements apply. Fatigue, infections, GI effects, and rash can occur. The overall profile depends heavily on the combination partner — pairing with a bispecific (elranatamab, teclistamab, talquetamab) adds cytokine release syndrome and infection risk from that agent. This is general information; iberdomide is investigational and its final labeled safety profile is not yet established.

Find Iberdomide and Multiple Myeloma Trials Matched to Your Situation

Use ClinTrialFinder's AI-powered matching to find iberdomide and other multiple myeloma trials based on your prior treatments (lenalidomide, pomalidomide, anti-CD38, prior BCMA therapy, CAR-T), transplant status, and disease stage.

Find Matching Trials

This page is for information only and is not medical advice. Iberdomide (Zenbexus) is FDA-approved for multiple myeloma after at least one prior line of therapy (the ZDd regimen) and remains investigational in earlier settings; nothing here should be read as guidance on efficacy for your situation. Enrollment and treatment decisions should always be made with your oncologist or hematologist. Trial eligibility, recruitment status, and regulatory status can change — verify directly with the trial sponsor, the FDA prescribing information, or on ClinicalTrials.gov before acting on any information here.