Bristol Myers Squibb Reports Positive MRD Results For Iberdomide Combo In Phase 3 Multiple Myeloma Study

Bristol Myers Squibb announced positive interim findings from its Phase 3 EXCALIBER-RRMM trial evaluating iberdomide, an investigational CELMoD™, in combination with daratumumab and dexamethasone for relapsed or refractory multiple myeloma (RRMM). The study showed a statistically significant improvement in minimal residual disease (MRD) negativity rates compared to the control arm. Based on the Data Monitoring Committee’s recommendation, the trial will proceed without changes to assess progression-free survival (PFS), overall survival, and safety outcomes. 

“This result builds on our significant experience in both targeted protein degradation and developing new treatment options for patients living with multiple myeloma. Iberdomide represents the first of a novel class of medicines, called CELMoDs, which have the potential to create a new foundation for multiple myeloma treatment that may be combined with other therapies,” said Anne Kerber, Senior Vice President, Head of Development, Haematology, Oncology and Cell Therapy. 

The EXCALIBER-RRMM study (NCT04975997) is a two-stage, open-label, randomized, global Phase 3 trial testing iberdomide with daratumumab and dexamethasone (IberDd) against the standard regimen of daratumumab, bortezomib, and dexamethasone (DVd). Stage 1 determined the optimal iberdomide dose of 1.0 mg, while Stage 2 is enrolling 664 patients to evaluate dual-primary endpoints of MRD negativity and PFS, along with secondary measures such as overall survival, response rates, and quality of life. The safety profile of iberdomide remains consistent with prior studies.

Minimal residual disease (MRD) refers to small clusters of cancer cells that evade detection using traditional diagnostic tools. In multiple myeloma, MRD testing has become a highly sensitive method to measure treatment success and predict long-term outcomes. Advanced techniques like next-generation sequencing (NGS) and flow cytometry (NGF) can detect one cancer cell among 100,000 to 1,000,000 normal cells, providing unprecedented precision. MRD is increasingly used in clinical trials as a surrogate endpoint for PFS and is gaining regulatory recognition for its role in accelerating new treatment approvals.