FDA Approval

FDA Grants Accelerated Approval to Zenbexus for Previously Treated Multiple Myeloma

Edited by:
Anthony Calabro, MA

Key Highlights

  • The FDA approved iberdomide with daratumumab, hyaluronidase-fihj, and dexamethasone for adults with multiple myeloma who received at least 1 prior line of therapy that included a proteasome inhibitor and an immunomodulatory agent.
  • Accelerated approval was based on minimal residual disease (MRD)-negative complete response (CR) in the phase 3 EXCALIBER-RRMM trial.
  • MRD-negative CR occurred in 41% of patients receiving the iberdomide regimen compared with 21% receiving daratumumab, bortezomib, and dexamethasone (P < .0001).
  • Boxed warnings address embryo-fetal toxicity and serious venous and arterial thromboembolism.

On August 13, 2026, the FDA granted accelerated approval to iberdomide (Zenbexus (iberdomide; Bristol Myers Squibb) in combination with daratumumab, hyaluronidase-fihj, and dexamethasone for adults with multiple myeloma who received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent. Iberdomide is the first FDA-approved cereblon-modulating protein degrader, or CELMoD, for multiple myeloma. Continued approval may depend on verification and description of clinical benefit in confirmatory trials. Iberdomide was granted Breakthrough Therapy Designation, and the FDA review was conducted under Project Orbis.

Approval was supported by the phase 3, multicenter, randomized, open-label EXCALIBER-RRMM trial, which compared iberdomide plus daratumumab, hyaluronidase-fihj, and dexamethasone with daratumumab, bortezomib, and dexamethasone in patients with relapsed or refractory multiple myeloma. The trial has dual primary endpoints of minimal residual disease (MRD) negativity and progression-free survival. In the primary MRD efficacy population, MRD-negative CR was achieved by 41% of patients receiving the iberdomide regimen (85 of 207; 95% CI, 34%-48%) compared with 21% receiving the comparator regimen (44 of 213; 95% CI, 15%-27%; P < .0001) at a median follow-up of 16 months. The progression-free survival endpoint remains under evaluation.

Among patients receiving the iberdomide regimen, neutropenia occurred in 90.2% and infections in 78.9%. Serious adverse reactions occurred in 58.3% of patients, including pneumonia in 26%, upper respiratory tract infection in 6.4%, second primary malignancy in 5.9%, neutropenia in 4.9%, COVID-19 in 4.4%, febrile neutropenia in 3.9%, and sepsis in 2.9%. Fatal adverse reactions occurred in 4.9% of patients. The prescribing information carries boxed warnings for embryo-fetal toxicity and serious venous and arterial thromboembolism; iberdomide is contraindicated during pregnancy and is available through the ZENBEXUS REMS restricted distribution program.

In EXCALIBER-RRMM, the primary efficacy population received iberdomide 1 mg as part of the combination regimen, with treatment continued until disease progression or unacceptable toxicity.

Reference
Bristol Myers Squibb. U.S. FDA grants accelerated approval to Bristol Myers Squibb's first CELMoD therapy ZENBEXUS™, in combination with daratumumab and hyaluronidase-fihj and dexamethasone (ZDd) for patients with multiple myeloma, as early as first relapse. Published August 13, 2026. Accessed August 17, 2026. https://news.bms.com/news/corporate-financial/2026/U-S--FDA-Grants-Accelerated-Approval-to-Bristol-Myers-Squibbs-First-CELMoD-Therapy-ZENBEXUS-in-Combination-with-Daratumumab-and-Hyaluronidase-fihj-and-Dexamethasone-ZDd-for-Patients-with-Multiple-Myeloma-as-Early-as-First-Relapse/default.aspx