Iberdomide Plus Daratumumab and Dexamethasone Significantly Improves PFS in Relapsed or Refractory Multiple Myeloma

Clinical Summary: 

• Design/Population: The phase 3 EXCALIBER-RRMM trial compared iberdomide plus daratumumab and dexamethasone with daratumumab, bortezomib, and dexamethasone in 800 patients with relapsed or refractory multiple myeloma who had received 1 or 2 prior lines of therapy.
• Key Outcomes: Iberdomide plus daratumumab and dexamethasone significantly prolonged median progression-free survival (PFS) compared with the control regimen, reducing the risk of disease progression or death by 51%. The findings build on previously reported improvements in MRD-negative complete response, the trial's other dual primary end point.
• Clinical Relevance: The PFS improvement provides additional evidence supporting iberdomide-based treatment in relapsed or refractory multiple myeloma following its accelerated FDA approval based on MRD-negative complete response. The findings also strengthen the evidence for using the combination as early as first relapse.

Topline results from the phase 3 EXCALIBER-RRMM trial demonstrated that iberdomide plus daratumumab and dexamethasone significantly improved progression-free survival (PFS) compared with daratumumab, bortezomib, and dexamethasone in patients with relapsed or refractory multiple myeloma.

EXCALIBER-RRMM is a multicenter, randomized, open-label phase 3 trial evaluating iberdomide plus daratumumab and dexamethasone against daratumumab, bortezomib, and dexamethasone in adults with relapsed or refractory multiple myeloma who had received 1 or 2 prior lines of therapy and experienced disease progression.

The trial included a dose-optimization stage, followed by a confirmatory efficacy analysis. A total of 800 patients were randomized to receive iberdomide plus daratumumab and dexamethasone (n = 400) or daratumumab, bortezomib, and dexamethasone (n = 400). Treatment continued until disease progression or unacceptable toxicity. The dual primary end points were MRD negativity and PFS. Secondary end points included overall survival (OS), objective response rate (ORR), safety, and sustained MRD negativity.

At a median follow-up of 23 months, median PFS was 42 months with iberdomide plus daratumumab and dexamethasone compared with 20 months with daratumumab, bortezomib, and dexamethasone. The iberdomide-containing regimen reduced the risk of disease progression or death by 51% compared with the control regimen (hazard ratio [HR], 0.49; P < .000001), meeting the PFS component of the trial's dual primary end points.

The updated PFS findings build on earlier EXCALIBER-RRMM results demonstrating superior MRD-negative complete response with iberdomide plus daratumumab and dexamethasone. Those findings supported the combination's accelerated FDA approval, with continued approval potentially contingent upon verification of clinical benefit.

Detailed MRD findings were previously presented at the 2026 International Myeloma Society Annual Meeting and published in Lancet Oncology.

The safety profile of iberdomide plus daratumumab and dexamethasone remained consistent with earlier findings. Detailed safety results from the updated PFS analysis were not provided in the topline announcement.

The updated findings provide evidence that the previously observed improvement in MRD-negative complete response with iberdomide plus daratumumab and dexamethasone is accompanied by longer PFS compared with daratumumab, bortezomib, and dexamethasone.

Detailed results from the PFS analysis are planned for presentation at the 2026 American Society of Hematology (ASH) Annual Meeting.

Source: 

Bristol Myers Squibb. Bristol Myers Squibb Announces ZENBEXUS (iberdomide) in combination with daratumumab and dexamethasone (ZDd) demonstrates superior progression-free survival vs. standard of care in relapsed and refractory multiple myeloma in phase 3... Accessed on: October 8, 2026. https://news.bms.com/news/corporate-financial/2026/Bristol-Myers-Squibb-Announces-ZENBEXUSTM-iberdomide-in-Combination-with-Daratumumab-and-Dexamethasone-ZDd-Demonstrates-Superior-Progression-Free-Survival-vs--Standard-of-Care-in-Relapsed-and-Refractory-Multiple-Myeloma-in-Phase-3---/default.aspx