Multiple myeloma is a cancer that starts in plasma cells, a type of white blood cell made in your bone marrow. Over time, the abnormal plasma cells multiply, crowding out healthy blood cells. This may lead to bone pain, tiredness, and frequent infections. Multiple myeloma often goes into remission with treatment, but for most people, it comes back (relapses) or stops responding to treatment (becomes refractory). Each time this happens, a new treatment plan is usually needed.
How Does Zenbexus Work for Multiple Myeloma?
Myeloma cells rely on two proteins, Aiolos and Ikaros, to survive and multiply. Zenbexus works by attaching to a protein in your cells called cereblon. Cereblon is part of a system your cells use to tag other proteins for destruction. Once Zenbexus attaches to cereblon, it directs that system to break down Aiolos and Ikaros.
Without Aiolos and Ikaros, myeloma cells are more likely to die off. Breaking down these two proteins also helps wake up your immune system; this allows your natural killer cells and T cells (immune cells that can attack cancer) to work better and stay active longer.
Zenbexus binds to cereblon more tightly than older medicines such as lenalidomide and pomalidomide. That tighter grip allows it to break down Aiolos and Ikaros in a better way, so researchers consider Zenbexus to have stronger anticancer and immune-boosting effects than those older medicines. Lab studies show that Zenbexus can also kill myeloma cells that have already become resistant to lenalidomide or pomalidomide.
Lab studies also show that when Zenbexus is taken with daratumumab, the two medicines work together to help the immune system find and destroy myeloma cells better than either medicine alone.
How Do I Take Zenbexus?
Zenbexus comes as a capsule you take by mouth once a day, with or without food. It is taken on days 1 through 21 of a 28-day cycle. You'll also receive daratumumab/hyaluronidase-fihj and dexamethasone. You will likely continue this combination as long as it's working and side effects stay manageable.
A few things to know:
- Swallow the capsule whole with water. Don't open, break, or chew it.
- Avoid touching the contents of the capsule. If you touch a broken capsule or its contents, quickly wash the area thoroughly with soap and water.
- If you miss a dose and it's been less than 12 hours since the dose was missed, take it as soon as you remember. If it's been more than 12 hours, skip that dose and take your next one as scheduled. Never take two doses at once.
- If you have reduced kidney function, your health care provider may prescribe a lower dose.
Because Zenbexus can cause serious birth defects if taken during pregnancy, it's only available through a restricted program called the Zenbexus Risk Evaluation and Mitigation Strategy (REMS) Program. Both you and your health care provider must enroll before you can start treatment, and the medicine can only be dispensed by certified pharmacies. You can learn more at www.ZenbexusREMS.com or by calling the REMS Call Center at 888-423-5436. Read more about this program, along with Zenbexus's other risks, in this article on Zenbexus side effects and interactions.
Is Zenbexus Right for Me?
Zenbexus, with daratumumab/hyaluronidase-fihj and dexamethasone, is FDA-approved for adults with multiple myeloma who have already tried at least one other treatment regimen that included both a proteasome inhibitor (such as bortezomib) and an immunomodulatory medicine (such as lenalidomide).
Zenbexus received what’s called an "accelerated approval" from the FDA. That means the FDA cleared the medicine based on an early but strong signal of benefit rather than waiting for longer-term survival data. Continued approval for this use may depend on results from further studies confirming that this early signal translates into a lasting clinical benefit.
Your health care provider will consider things such as your prior treatments, how you tolerated them, and your overall health when deciding if Zenbexus is a good fit for you.
How Was Zenbexus Studied for Multiple Myeloma?
Zenbexus was studied in a large, ongoing international study called EXCALIBER-RRMM. The study was designed in two parts.
- The first part tested three different doses of Zenbexus to find the dose that would be best to study further.
- The second part compared that selected dose of Zenbexus (combined with daratumumab/hyaluronidase-fihj and dexamethasone) against a different three-medicine combination — daratumumab/hyaluronidase-fihj plus bortezomib plus dexamethasone.
EXCALIBER-RRMM is an open-label study, meaning both participants and their care teams knew which treatment they were getting. The results below come from the first 420 people who were enrolled and randomly assigned to one of the two combinations, using the Zenbexus dose that was ultimately selected (1 mg once daily).
Here are the characteristics of study participants:
- At the start of the study, participants were, on average, in their late 60s (ages 35-87), and 42% were female.
- About 6 in 10 participants were White, 1% were Black, and around a third were Asian. About 2% were Hispanic or Latino.
- Everyone had multiple myeloma that had relapsed or become refractory after one or two prior treatment regimens; two-thirds had tried one prior treatment regimen, and the rest had tried two. Almost all participants (95%) had previously received a proteasome inhibitor, and 9 in 10 had previously received an immunomodulatory medicine such as lenalidomide.
- People whose myeloma no longer responded to a prior daratumumab-type medicine or bortezomib were not included in this part of the study.
What Are the Main Benefits of Zenbexus Based on This Study?
The main goal of this part of the study was to see how many people reached a complete response (essentially no detectable signs of myeloma using standard tests), with no trace of remaining cancer cells found using a highly sensitive lab test. This is called a minimal residual disease (MRD)-negative complete response.
Significantly more people reached an MRD-negative complete response with Zenbexus, daratumumab/hyaluronidase-fihj, and dexamethasone (41%) than with daratumumab/hyaluronidase-fihj, bortezomib, and dexamethasone (21%). Among people in either group who reached a complete response, the majority (89% with the Zenbexus combination and 83% with the comparison combination) had no detectable trace of remaining cancer cells.
The study is ongoing to look at progression-free survival, which measures how long people live without their cancer getting worse.
Your results may differ from what was seen in clinical studies.
How Long Was the Study? Is There Longer-Term Data?
EXCALIBER-RRMM is still ongoing, and people continue treatment with Zenbexus for as long as it's working and side effects are manageable, rather than for a fixed number of cycles. Among people treated with Zenbexus so far, 86% have taken it for six months or longer, and 73% for more than a year. This gives researchers a meaningful amount of real-world, longer-term safety experience to draw on beyond just the initial cycles.
What Do I Need to Do to Get Zenbexus?
Because of the Zenbexus REMS Program described above, you'll need to enroll and sign a Patient Enrollment Form, and your prescriber and pharmacy must also be certified in the program. Zenbexus is typically prescribed by a hematologist or oncologist experienced in treating multiple myeloma.
Is There Cost Assistance Available for Zenbexus?
The drugmaker offers a copay savings program for some people with insurance, as well as resources to help people explore other financial assistance options. Ask your health care provider's office or the pharmacy dispensing Zenbexus about current program details, or visit the drugmaker's Zenbexus website to learn more
