Zenbexus (iberdomide) for multiple myeloma
Fact-checked by What is Zenbexus for multiple myeloma?
Zenbexus (iberdomide) is an oral therapy approved to be used as part of a treatment combination for adults with multiple myeloma who have previously received at least one line of treatment, including a proteasome inhibitor and an immunomodulatory agent. The therapy received accelerated approval in the U.S., meaning its continued approval may depend on additional evidence confirming its clinical benefit.
Multiple myeloma occurs when plasma cells, a type of immune cell, grow out of control in the bone marrow, the spongy tissue inside some bones.
Zenbexus belongs to a class of next-generation immunomodulatory drugs called cereblon E3 ligase modulatory drugs, or CELMoDs. It works by binding to the protein cereblon, which is involved in the system that marks defective and abnormal proteins for recycling.
This binding enables more efficient tagging of proteins that support myeloma cell survival, speeding their degradation. Without these necessary proteins, myeloma cells die. The medication also stimulates the immune system to further attack cancerous cells.
Bristol Myers Squibb, the developer of Zenbexus, received accelerated approval for this indication based on the rate of minimal residual disease (MRD)-negative complete response in the Phase 3 EXCALIBER-RRMM trial. Continued approval may depend on confirmation of clinical benefit in ongoing trial(s). Additionally, Bristol Myers Squibb is testing the medication in other myeloma contexts, including in people who have recently received a stem cell transplant.
Therapy snapshot
| Brand name | Zenbexus |
| Chemical name | Iberdomide |
| Usage | Used for certain adults with multiple myeloma |
| Administration | Oral capsules |
Who can take Zenbexus?
In the U.S., Zenbexus’ accelerated approval covers adults with multiple myeloma who have received at least one prior line of treatment, including a proteasome inhibitor and an immunomodulatory agent. Zenbexus is specifically indicated to be used in combination with the approved antibody-based therapy Darzalex Faspro (daratumumab and hyaluronidase-fihj) and the corticosteroid dexamethasone.
The prescribing information for Zenbexus includes two boxed warnings — one noting the medication can harm a developing fetus, and the other highlighting a risk of serious blood clots in veins or arteries. As a result, Zenbexus is contraindicated during pregnancy and preventive anti-clotting treatment is recommended. Additionally, Zenbexus is only available in the U.S. through a restricted distribution program called Zenbexus Risk Evaluation and Mitigation Strategy (REMS).
How is Zenbexus administered?
Zenbexus comes as oral capsules that should be taken at approximately the same time each day, with or without food. The capsules should be swallowed whole; they should not be opened, broken, or chewed.
The recommended dosage is 1 mg once daily for the first three weeks of a four-week treatment cycle. Treatment should continue until the disease progresses or side effects become intolerable.Â
Dose adjustments are needed for some people with impaired kidney function who are not on dialysis. Adjustments may also be needed for those taking medications that strongly or moderately inhibit the activity of CYP3A, an enzyme that breaks down Zenbexus in the body, when using both medications is unavoidable. Zenbexus is also generally avoided with strong or moderate CYP3A inducers, which can reduce exposure to the medication and make it less effective.
Zenbexus in clinical trials
Zenbexus’ accelerated approval in the U.S. was primarily supported by data from the ongoing Phase 3 EXCALIBER-RRMM trial (NCT04975997), which included adults with multiple myeloma that had returned (relapsed) or failed to respond (refractory) to prior therapies. A total of 939 patients who had previously received one or two lines of treatment were randomized in the trial. Participants were randomly assigned to receive dexamethasone and Darzalex Faspro, in combination with either Zenbexus or bortezomib (sold as Velcade and generics).
Data showed that more people in the Zenbexus group achieved a minimal residual disease (MRD)-negative complete response, meaning no myeloma cells were detected using a highly sensitive test. Among the first 420 participants included in this analysis, 41% of those in the Zenbexus group achieved this clinical milestone — significantly more than the 21% in the bortezomib group.
Another Phase 3 clinical trial called EXCALIBER-Maintenance (NCT05827016) is also underway to assess the effectiveness of Zenbexus as maintenance therapy after a stem cell transplant in people with newly diagnosed multiple myeloma, compared with Revlimid (lenalidomide).
Zenbexus side effects
The most common side effects of Zenbexus, when given alongside Darzalex Faspro and dexamethasone, include:
- upper respiratory tract infection
- fatigue
- muscle or bone pain
- pneumonia
- diarrhea
- movement problems
- rash
- sleep disorders
- low levels of protective antibodies in the blood (hypogammaglobulinemia)
- COVID-19
- constipation
Zenbexus may also cause reductions in blood cell counts.
The therapy’s boxed warning notes that Zenbexus can harm developing fetuses and may cause birth defects. Therefore, it is contraindicated in pregnancy. The REMS program helps manage this risk, and females of reproductive potential who can get pregnant need to:
- have two negative pregnancy tests before starting treatment with Zenbexus
- receive regular pregnancy tests during treatment
- use two effective forms of contraception, or abstain from heterosexual intercourse, for at least four weeks before treatment, throughout treatment, and for at least four weeks after the last dose
- not donate eggs during treatment and for four weeks after completing treatment
The medication can also pass into semen, so men who have sexual intercourse with partners who can get pregnant need to use an effective method of contraception throughout treatment and for four weeks after the last dose. They should also not donate sperm during this time.
Additionally, Zenbexus can increase the risk of blood clots, which can block circulation and lead to complications including heart attacks and strokes. Preventive anti-clotting treatment is recommended during treatment. If patients develop one of these blood clots, Zenbexus should be interrupted and anticoagulant treatment started according to guidelines.
Zenbexus can also cause neutropenia, or low levels of a type of white blood cell called neutrophils. This can leave the body vulnerable to serious, life-threatening, or fatal infections. Regular blood count testing and monitoring for signs of infection can help manage these risks. Doctors will also monitor patients for other types of cancer, which can arise in some patients.
Rare Cancer News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
