Iberdomide combined with standard therapies showed a statistically significant improvement in minimal residual disease (MRD) negativity rates, compared with the control arm, in patients with relapsed or refractory multiple myeloma, according to a news release from Bristol Myers Squibb.
Results come from the phase 3 trial EXCALIBER-RRMM which evaluated iberdomide, an investigational cereblon E3 ligase modulator (CELMoD), combined with Darzalex (daratumumab) plus dexamethasone.
“This result builds on our significant experience in both targeted protein degradation and developing new treatment options for patients living with multiple myeloma,” Anne Kerber, senior vice president, head of Development, Hematology, Oncology and Cell Therapy, said in the news release. “Iberdomide represents the first of a novel class of medicines, called CELMoDs, which has the potential to create a new foundation for multiple myeloma treatment that may be combined with other therapies.”
The study will continue as planned to measure how long patients live without their cancer getting worse (progression-free survival), as well as how long patients live overall (overall survival) and to monitor safety. Up until now, the safety of iberdomide with Darzalex and dexamethasone looks similar to what has been seen in previous studies.
EXCALIBER-RRMM Study Details
The study is designed to measure two main goals: minimal residual disease negativity and progression-free survival. Other goals being studied include overall survival, overall response rate, duration of response, time to progression, time to next treatment and health-related quality of life.
In stage 1 of the study, iberdomide at one milligram was chosen as the best dose based on safety, how the body processes the drug, and how well it worked. In stage 2, about 664 patients were randomly assigned to receive either iberdomide plus Darzalex and dexamethasone or Darzalex, Velcade (bortezomib) and dexamethasone.
What are Targeted Protein Degradation and Novel CELMoD Agents?
Targeted protein degradation is a type of research that focuses on breaking down specific proteins in the body that play a role in disease. Some of these proteins were once thought to be “undruggable,” meaning they could not be targeted with medicines. By removing harmful proteins rather than just blocking them, this approach can open up new ways to treat cancer and other diseases.
The first medicines using this strategy were called immunomodulatory drugs. These medicines work by helping the immune system attack cancer and have become a standard treatment for multiple myeloma. Building on this, researchers are now studying several new kinds of protein degraders in clinical trials:
- CELMoD agents: a newer generation of immunomodulatory drugs that are designed to be more precise and potentially more effective.
- Ligand-directed degraders: medicines that guide the body to break down harmful proteins by attaching to them directly.
- Degrader antibody conjugates: a newer type of treatment that links a protein degrader to an antibody, which helps deliver the drug to the exact place it needs to go.
Using these different approaches allows scientists to match the right type of medicine to the way a disease works. The goal is to create more options for patients, not only in blood cancers like multiple myeloma but also in many other diseases.
What is Minimal Residual Disease?
After treatment, some people may still have very small amounts of myeloma cells in their body that cannot be found with standard tests. This is called minimal residual disease. Even though it does not always mean the cancer is gone, reaching minimal residual disease negativity is often linked with longer periods of remission and better survival.
Current advanced testing methods can spot a single cancer cell hidden among hundreds of thousands to millions of healthy cells, according to the release. Because of this level of detail, minimal residual disease testing is becoming an important way to measure treatment success. Researchers are also using it in clinical trials to better understand how new treatments may help patients sooner.
Reference
- “Bristol Myers Squibb Announces Phase 3 EXCALIBER-RRMM Study Evaluating Iberdomide in Combination with Standard Therapies Demonstrated a Significant Improvement in Minimal Residual Disease Negativity Rates in Relapsed or Refractory Multiple Myeloma.” Bristol Myers Squib. News Release. Sep 23, 2025.
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