What To Know About CELMoDs For Multiple Myeloma
- When multiple myeloma comes back after standard treatments like lenalidomide and daratumumab, patients often need new options, and early clinical trial results show that a drug called mezigdomide may help fill that gap.
- Mezigdomide is an off‑the‑shelf medicine, meaning treatment can start quickly and may help control the disease while patients consider more complex therapies like CAR T‑cell treatment.
- The SUCCESSOR-2 trial compared the addition of mezigdomide to the standard treatment of carfilzomib and dexamethasone. Patients in the mezigdomide group achieved a median of 18 months without their disease progressing (also called progression-free survival (PFS), compared with 8.3 months for the standard group, which more than doubles the PFS.
- Though more follow-up is needed, researchers hope this new drug can help the immune system keep fighting myeloma even after older medicines stop working.
Multiple myeloma remains a cancer that requires several different therapies over time. New results from a clinical trial, presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting—one of the world’s largest and most influential meetings of cancer specialists and researchers—suggest that a new drug called mezigdomide [an experimental pill developed by by Bristol Myers Squibb] may help fill an important treatment gap for patients whose disease has returned after standard therapies.
Read MoreThis study (SUCCESSOR-2) evaluated the drug mezigdomide in combination with other known medications (carfilzomib, a prescription medication known by its brand name Kyprolis and dexamethasone, an cortisone-like medicine or steroid) in patients with multiple myeloma that has recurred.
“SUCCESSOR-2 is the first randomized, phase 3 trial in relapsed/refractory myeloma to report on the benefit of mezigdomide-based therapy, and the findings are really quite remarkable and very encouraging,” Dr. Paul Richardson, of Dana-Farber Cancer Institute, tells SurvivorNet.
WATCH: The Story of Lenalidomide: A Major Advance in Treatment
All of the patients in the study had previously been treated with lenalidomide (brand name: Revlimid), one of the most commonly used myeloma medications, as well as another drug, daratumumab, known as Tec-Dara. Tec-Dara is an injection-only immunotherapy combination that does not include chemotherapy.
These are treatments that many patients receive early in their care, creating a growing need for effective options once the disease becomes resistant to them.
The trial compared the addition of mezigdomide to the standard treatment of carfilzomib and dexamethasone. Patients in the mezigdomide group achieved a median of 18 months without their disease progressing (progression-free survival), compared with 8.3 months for the standard group. This more than doubles the progression-free survival, which is the period of time between the treatment beginning and its efficacy wearing off.
What is Mezigdomide?
Mezigdomide belongs to a newer class of drugs known as CELMoDs. These medicines are designed to work in a similar way to lenalidomide while overcoming some of the resistance that can develop over time.
In simple terms, researchers hope mezigdomide can help the immune system continue recognizing and fighting myeloma cells even when older therapies are no longer working as well as they once did.
Dr. Richardson likes to use an example from Star Wars as a metaphor for how the drugs work.
“Do you remember ‘Return of the Jedi’ and the Death Star sitting off of that lovely planet with the Ewok? Well, you may remember Han Solo and Chewbacca shoot something right into the center of the Death Star and it goes to pieces and then all the federation ships come in,” he explains.
“…That’s exactly what mezigdomide does. It nails the Death Star and then all the federation starships come in to finish off the bad guys.”
Treatment Sequencing
Thanks to advances in treatment, many people with multiple myeloma are living longer than ever before. However, as patients move through different lines of therapy, doctors must determine which treatment should come next.
Newer options such as CAR T-cell therapy (a powerful immunotherapy) and bispecific antibodies (a type of immune therapy) have produced remarkable results, but they can also involve specialized treatment centers, complex logistics, and unique side effects.
CAR T-Cell Therapy: Hope, Hurdles, and What to Expect
Not every patient can access these therapies immediately, and some may need another effective treatment option before moving on to those approaches. If these results continue to be positive, mezigdomide could provide that option.
Since it is an “off-the-shelf” therapy, treatment can generally begin without the delays associated with personalized therapies. For patients, this could mean having another effective way to control their disease while preserving future treatment choices.
Looking Ahead
While longer follow-up is still needed to fully understand the benefits and side effects of mezigdomide, this trial represents encouraging news for patients whose myeloma has returned after lenalidomide-based treatment.
In a disease where having more options can make a meaningful difference, the development of mezigdomide may offer patients and their care teams another valuable tool for keeping myeloma under control and extending the time before more intensive therapies are needed.
Expert Resources for Multiple Myeloma Patients
- “An Important Step”: FDA Approves New Combination Treatment For Newly Diagnosed Multiple Myeloma Patients
- A Great New Option For Multiple Myeloma Patients: Daratumumab Now Available As a Quick Shot, Replacing Long Infusions
- Adding Daratumumab to Front-line Therapy in Multiple Myeloma
- Adding Sarclisa to Treatment– A Promising New Option for Relapsed Multiple Myeloma
- Advocating for Yourself is the Most Important Thing: Multiple Myeloma Survivor Ann Bogle's Story
Understanding Multiple Myeloma
Multiple myeloma is a rare and incurable type of blood cancer. When you have this cancer, white blood cells called plasma cells (the cells that make antibodies to fight infections) in your bone marrow grow out of proportion to healthy cells.
Those abnormal cells leave less room for your body’s healthy blood cells to fight infections. They can also spread to other parts of your body and cause problems with organs like your kidneys.
“In general, having blood cancer means that your bone marrow is not functioning correctly,” Dr. Nina Shah, a hematologist at UCSF, explained to SurvivorNet.
Known risk factors for multiple myeloma include your age, family history of cancer, and whether you have monoclonal gammopathy of undetermined significance (MGUS). MGUS is a condition that occurs when you have too much monoclonal protein in your blood and bone marrow.
Most people diagnosed are in their 60s. However, people younger than 60 can also get this type of cancer, and if you have a close relative with multiple myeloma, that can increase your risk.
WATCH: Recognizing multiple myeloma symptoms.
Multiple myeloma can cause symptoms such as weakness, dizziness, bone pain, and confusion, among other symptoms.
Doctors use blood and urine tests and imaging tests such as X-rays or MRIs to help diagnose multiple myeloma and to guide treatment options. Ultimately, a bone marrow biopsy will confirm the diagnosis.
Options When Multiple Myeloma Relapses
When your multiple myeloma comes back within about a year, your disease is generally classified as “high risk.”
When multiple myeloma returns after treatment, it usually means that there were residual cells, even in very small numbers, that were either resistant to the treatment from the start or acquired resistance over time.
In other words, not every myeloma cell in your body is precisely the same. Some start with a set of mutations that can give them resistance to treatments and make them more likely to relapse, whereas others develop mutations as a result of treatment.
When multiple myeloma relapses or stops responding to treatments, there are still options, and the research into mezigdomide aims to create another one of those for patients.
Questions To Ask Your Doctor
- Is there a benefit to using mezigdomide over something like CAR T-cell therapy?
- Should I consider enrolling in a clinical trial?
- What are the potential side effects of CELMoDs?
- How will I be monitored for recurrence?
Learn more about SurvivorNet's rigorous medical review process.
