Frequently asked questions on the FDA-accelerated approval of Zenbexus (iberdomide), in combination with multiple myeloma indications
On Thursday, August 13, the U.S. 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.
(EDITOR'S NOTE: This blog article was medically reviewed by Joseph Mikhael, MD, MEd, FRCPC, FACP, FASCO, on October 14, 2026. The article reflects medical guidance available at the time of review and is not routinely updated.)
1. What is Zenbexus? What is its generic name?
Zenbexus is the brand name for iberdomide, developed by Bristol Myers Squibb (BMS).
Iberdomide is the first cereblon-modulating protein degrader (CELMoD) for multiple myeloma that received accelerated approval from the FDA.
In the EXCALIBER-RRMM clinical trial, the iberdomide-based combination is referred to as IberDd — iberdomide in combination with daratumumab and hyaluronidase-fihj and dexamethasone.
2. What is an FDA accelerated approval?
An accelerated approval is a U.S. FDA regulatory pathway that can allow approval of a drug for a serious condition based on evidence involving a surrogate endpoint that is considered reasonably likely to predict clinical benefit.
For Zenbexus, the FDA's accelerated approval was based on minimal residual disease (MRD)-negative complete response (CR) at any time in the EXCALIBER-RRMM (NCT04975997) study.
Importantly, this accelerated approval does not mean that a benefit in progression-free survival (PFS) has already been confirmed.
The EXCALIBER-RRMM trial remains ongoing to assess PFS, one of the study's dual primary endpoints. The FDA states that continued approval may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
3. What are the specific indications for iberdomide under this FDA-accelerated approval?
The specific indication for this FDA-accelerated approval is Zenbexus (iberdomide), in combination with daratumumab and hyaluronidase-fihj and dexamethasone, indicated for the treatment of adults with multiple myeloma who have received at least one prior line of therapy that included a proteasome inhibitor and an immunomodulatory agent.
The indication was granted under accelerated approval based on MRD-negative CR at any time.
The approval therefore applies to the specified patient population; it does not state that patients must have received exactly one prior line of therapy.
The EXCALIBER-RRMM study enrolled adults with relapsed or refractory multiple myeloma (RRMM) who had received one or two prior lines of anti-myeloma therapy and had progressive disease. Patients whose disease was refractory to a prior anti-CD38 monoclonal antibody or to prior bortezomib were excluded from the study.
4. What efficacy and safety information from the FDA should myeloma patients take note of?
The principal efficacy finding supporting the accelerated approval was the rate of MRD-negative complete response at any time.
Among the first 420 patients in the primary efficacy population:
• 41% (85/207) receiving IberDd achieved MRD-negative CR.
• 21% (44/213) receiving daratumumab, bortezomib and dexamethasone (DVd) achieved MRD-negative CR.
• The 95% confidence intervals were 34–48% and 15–27%, respectively.
• The reported p-value was <0.0001.
The study remains ongoing to assess PFS; a completed PFS analysis demonstrating clinical benefit has NOT been reported.
While BMS describes MRD negativity as among the deepest measures of response in myeloma and states that it is considered predictive of improved PFS, this statement should not be interpreted as a report that IberDd has already demonstrated an improvement in PFS.
Important safety concerns identified in the FDA information include:
• Embryo-fetal toxicity
• Serious venous and arterial thromboembolism
• Severe neutropenia
• Serious infections
• Second primary malignancies
Because of the risk of embryo-fetal toxicity, Zenbexus is available only through the restricted ZENBEXUS Risk Evaluation and Mitigation Strategy (REMS) program.
5. What is the FDA Risk Evaluation and Mitigation Strategies Program?
According to the FDA, “a Risk Evaluation and Mitigation Strategy (REMS) is a drug safety program that the U.S. Food and Drug Administration (FDA) can require for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks. REMS are designed to reinforce medication use behaviors and actions that support the safe use of that medication. While all medications have labeling that informs health care stakeholders about medication risks, only a few medications require a REMS.”
“REMS are not designed to mitigate all the adverse events of a medication, these are communicated to health care providers in the medication’s prescribing information. Rather, REMS focus on preventing, monitoring and/or managing a specific serious risk by informing, educating and/or reinforcing actions to reduce the frequency and/or severity of the event.”
6. What is the recommended dosage for Zenbexus (iberdomide)?
The recommended dose of Zenbexus ( iberdomide) is 1 mg orally once daily, with or without food, on Days 1 through 21 of each 28-day cycle, in combination with daratumumab and hyaluronidase-fihj and dexamethasone.
The regimen described in the FDA information is:
• Daratumumab and hyaluronidase-fihj: 1,800 mg subcutaneously on Days 1, 8, 15 and 22 of Cycles 1–2; Days 1 and 15 of Cycles 3–6; and Day 1 of Cycles 7 and beyond.
• Dexamethasone: 20 mg or 40 mg orally on Days 1, 8, 15 and 22.
• Treatment should continue until disease progression or unacceptable toxicity.
For patients with eGFR <30 mL/min/1.73 m² who are not on dialysis, the iberdomide dose should be reduced. If dose modification is required because of adverse events, the supplied prescribing information specifies 1 mg every other day on Days 1–21 of a 28-day cycle.
Patients should follow the dose prescribed by their oncology team rather than changing the dose themselves.
For a 0.75 mg reduced dose, take one 0.75 mg Zenbexus (iberdomide) capsule by mouth once daily on Days 1-21 of each 28-day cycle, with or without food, unless your prescriber gives a different instruction.
How to take it
• Take it at about the same time each day.
• Swallow the whole capsule with water; do not open, break, or chew it.
• If a dose is missed by less than 12 hours, take it when remembered. If more than 12 hours have passed, skip it. Do not double the next dose.
For U.S. full prescribing information on Zenbexus (iberdomide), you may view or download it here.
Zenbexus (iberdomide) should continue only until disease progression or unacceptable toxicity, alongside daratumumab and hyaluronidase-fihj plus dexamethasone.
7. What is the overall safety profile for Zenbexus (iberdomide)?
The reported safety profile included frequent neutropenia, infections, and other adverse reactions, as well as serious and potentially life-threatening risks.
In the EXCALIBER-RRMM study, 58.3% of patients receiving IberDd experienced serious adverse reactions, and 7.8% discontinued IberDd because of adverse reactions.
In the IberDd arm:
• Neutropenia occurred in 90.2% of patients overall; Grade 3 occurred in 30.9% and Grade 4 in 53.4%.
• Infections, including opportunistic infections, occurred in 78.9%; Grade 3 occurred in 35.8%, Grade 4 in 3.4%, and serious infections in 40%.
• Febrile neutropenia occurred in 5.4%.
• Second primary malignancies occurred in 6.9% at a median follow-up of 16 months. 6.9% at a median follow-up of 16 months.
Fatal adverse reactions occurred in 10 patients (4.9%) receiving Zenbexus. Sepsis (1.5%) was the only fatal drug reaction reported in more than one patient.
8. What are the common and possible adverse reactions or side effects?
The most common adverse reactions, defined in the supplied information as occurring in at least 20% of patients in the IberDd arm, were:
• Upper respiratory tract infection: 54%
• Fatigue: 36%
• Musculoskeletal pain: 35%
• Pneumonia: 34%
• Diarrhea: 33%
• Motor dysfunction: 26%
• Rash: 26%
• Sleep disorder: 25%
• Hypogammaglobulinemia: 24%
• COVID-19: 23%
• Constipation: 20%
The FDA information also identifies important serious risks, which include embryo-fetal toxicity, venous and arterial thromboembolic events, severe neutropenia, serious infections, and second primary malignancies.
In EXCALIBER-RRMM, despite mandatory thromboembolism prophylaxis:
• Venous thromboembolic events: 6.4%
- Deep vein thrombosis (DVT): 3.4%
- Pulmonary embolism (PE): 1.5%
• Arterial thromboembolic events: 3.4%
- Myocardial infarction: 2.0%
- Stroke/cerebrovascular accident: 1.5%
Patients receiving Zenbexus are also subject to specific reproductive-safety requirements because of the risk of embryo-fetal toxicity. Zenbexus is contraindicated in pregnancy and is available only through the ZENBEXUS REMS program.
9. What notable clinical trial results became the basis for accelerated approval?
The FDA's accelerated approval was based on EXCALIBER-RRMM (NCT04975997), a Phase 3, multicenter, two-stage, randomized, open-label study evaluating IberDd in patients with RRMM.
The study randomized a total of 939 patients. The primary efficacy population for the MRD-negative CR analysis consisted of the first 420 patients randomized to:
• IberDd: 207 patients
• Daratumumab + bortezomib + dexamethasone (DVd): 213 patients
At a median follow-up of 16 months, MRD-negative CR at any time occurred in:
• 41% (85/207) of patients receiving IberDd; 95% CI, 34–48
• 21% (44/213) of patients receiving DVd; 95% CI, 15–27
• p<0.0001
The trial was designed with dual primary endpoints of MRD negativity and PFS, with additional endpoints including overall survival (OS), overall response rate (ORR), safety and sustained MRD negativity.
The study remains ongoing to assess PFS; no completed PFS analysis demonstrating clinical benefit has been reported.
Accordingly, the reported MRD-negative CR result is the efficacy finding described as the basis for the accelerated approval, while verification and description of clinical benefit remain part of the requirements associated with the accelerated-approval pathway.
10. What are some expert opinions about Zenbexus (iberdomide) that patients should be made aware of?
Sagar Lonial, MD, FACP, FASCO, EXCALIBER-RRMM lead investigator, International Myeloma Foundation (IMF) Vice Chairperson of the Board, IMF Scientific Advisory Board member, and Chief Medical Officer of the Winship Cancer Institute of Emory University, described the FDA approval as the arrival of a new therapeutic class for RRMM. He said the results from the CELMoD-based combination have the potential to provide a new treatment foundation in multiple myeloma.
Heather Cooper Ortner, IMF President and CEO, emphasized the importance of both length and quality of life and described the approval as expanding treatment options for patients facing their first relapse.
These comments represent individual expert or organizational perspectives. They should be distinguished from the objective clinical-trial findings and the FDA's regulatory determination.
Key facts for patients
Zenbexus (iberdomide) received FDA accelerated approval on August 13, 2026, in combination with daratumumab and hyaluronidase-fihj and dexamethasone for adults with relapsed/refractory multiple myeloma who have received at least one prior line of therapy that included a proteasome inhibitor and an immunomodulatory agent.
The approval was based specifically on MRD-negative complete response at any time in EXCALIBER-RRMM. In the primary efficacy population, MRD-negative CR was reported in 41% with IberDd versus 21% with DVd (p<0.0001).
The study remains ongoing to assess PFS. The MRD-negative CR result should therefore be understood as the efficacy finding supporting the accelerated approval, rather than as a reported demonstration of PFS or overall survival benefit.
Zenbexus has important safety risks, including embryo-fetal toxicity, serious venous and arterial thromboembolism, severe neutropenia, serious infections, and second primary malignancies. The drug is contraindicated in pregnancy and is available through the ZENBEXUS REMS because of embryo-fetal toxicity risk.
References:
FDA grants accelerated approval to iberdomide with daratumumab and hyaluronidase-fihj and dexamethasone for multiple myeloma. U.S. Food and Drug Administration news release. August 13, 2026.
U.S. FDA Grants Accelerated Approval to Bristol Myers Squibb's First CELMoD Therapy ZENBEXUS™, in Combination with Daratumumab and Hyaluronidase-fihj and Dexamethasone (ZDd) for Patients with Multiple Myeloma, as Early as First Relapse. Bristol Myers Squibb press release. August 13, 2026.
Risk Evaluation and Mitigation Strategies | REMS. U.S. Food and Drug Administration. Current as of May 20, 2025.
Package inserts, Zenbexus. Bristol Myers Squibb prescribing information.
