Zenbexus (iberdomide): FDA approval, pivotal trial and safety
Approved
Type
New molecular entity · Oral
FDA-approved use
To be used in combination with daratumumab and hyaluronidase-fihj and dexamethasone for adults with multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agentWording from FDA's list of novel approvals.
FDA review
Priority reviewOrphan drugAccelerated approval
Company
Bristol Myers Squibb
Application
NDA 221075
Specialty
Oncology
Boxed warning: Embryo-fetal toxicity and serious venous and arterial thromboembolism
At a glance
Zenbexus is the first cereblon E3 ligase modulator (CELMoD) approved, given with daratumumab and dexamethasone for multiple myeloma after at least one earlier line including a proteasome inhibitor and an immunomodulatory drug. In EXCALIBER-RRMM it doubled the rate of MRD-negative complete response compared with daratumumab, bortezomib and dexamethasone (41% versus 21%). The approval is accelerated: progression-free survival results are still to come.
What it is and how it works
Iberdomide binds cereblon, part of an E3 ubiquitin ligase, and directs the cell to destroy the transcription factors Ikaros and Aiolos. That kills myeloma cells and stimulates T and NK cells. It works like lenalidomide and pomalidomide but binds cereblon more tightly, and it was active against lenalidomide- and pomalidomide-resistant myeloma cells in the laboratory.
Phase 3, two-stage, open-label, randomized, controlled trial at 211 sites in 31 countries; MRD-negative complete response and progression-free survival are dual primary end points.
Patients
Adults with relapsed or refractory multiple myeloma after one or two earlier lines; the primary MRD analysis included the first 420 patients (median age 68). Anti-CD38- or bortezomib-refractory disease was excluded.
Compared with
Daratumumab, bortezomib and dexamethasone (DVd).
Primary endpoint
MRD-negative complete response at any time (primary analysis at 12 months or more of follow-up); progression-free survival is being assessed in 800 patients.
Result
MRD-negative complete response in 41% (85 of 207) versus 21% (44 of 213): difference 20.1 percentage points (95% CI, 11.5 to 28.6; P<0.0001); odds ratio 2.8 (95% CI, 1.8 to 4.3). Median follow-up 15.7 months.
Other results
Progression-free survival results are pending.
Safety in the trial
Grade 3 or 4 events 92% versus 70%, including neutropenia 84% versus 11% and infection 39% versus 22%; serious events 58% versus 41%, most often pneumonia (18% versus 6%).
How does Zenbexus (iberdomide) compare with the alternatives (Daratumumab, bortezomib and dexamethasone (DVd), Daratumumab, pomalidomide and dexamethasone, Carfilzomib-based triplets) for its approved use (to be used in combination with daratumumab and hyaluronidase-fihj and dexamethasone for adults with multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibit…? Summarize head-to-head and indirect evidence, efficacy, safety and where each fits, with citations.
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Safety signals
The boxed warning covers embryo-fetal toxicity and serious venous and arterial thromboembolism, as for other drugs of its family. In the trial, grade 3 or 4 adverse events occurred in 92% versus 70% with the comparator, driven by neutropenia (84% versus 11%) and infection (39% versus 22%); pneumonia was the most common serious event (18% versus 6%). Treatment-related deaths were 1% in each group.
What it competes with
After one to three earlier lines, options include daratumumab-based triplets with bortezomib, carfilzomib or pomalidomide, and CAR T-cell therapy for lenalidomide-refractory disease. EXCALIBER-RRMM excluded patients whose disease was refractory to an anti-CD38 antibody or to bortezomib.
Daratumumab, bortezomib and dexamethasone (DVd)The trial's comparator.
Daratumumab, pomalidomide and dexamethasoneAnother daratumumab triplet with an immunomodulatory drug.
Carfilzomib-based tripletsWith daratumumab or lenalidomide and dexamethasone.
Ciltacabtagene autoleucelCAR T-cell therapy after one or more lines in lenalidomide-refractory disease.
Bottom line for clinicians
For relapsed myeloma that is not refractory to daratumumab or bortezomib, iberdomide with daratumumab and dexamethasone gives deeper responses than DVd. Expect much more neutropenia and infection, consider infection prophylaxis and growth-factor support as in local practice, and remember that the survival benefit is not yet confirmed.
Dosing, contraindications and full warnings are in the prescribing information.
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Last updated October 27, 2026 by 2 Minute Medicine.
For healthcare professionals. A summary of public FDA documents and published trials, not medical advice. Check the full prescribing information before prescribing.
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