BMS’s First CELMoD Therapy ZENBEXUS™ Receives Accelerated FDA Approval in Combination with Daratumumab for Multiple Myeloma, Including Early Relapse Patients

August 17, 2026

Bristol Myers Squibb USA

Overview

The U.S. FDA granted accelerated approval to Bristol Myers Squibb’s first Cereblon E3 ligase modulator (CELMoD) therapy, ZENBEXUS™ (iberdomide), in combination with daratumumab, hyaluronidase-fihj, and dexamethasone (ZDd), for adult patients with multiple myeloma, including those in early first relapse. ZENBEXUS, which also holds Breakthrough Therapy Designation, was evaluated for efficacy based on the minimal residual disease (MRD)-negative complete response (CR) rate in the Phase 3 EXCALIBER-RRMM study. This represents a groundbreaking advance in the treatment paradigm for multiple myeloma, offering new hope for deep and durable responses.

In Depth

Key Findings

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to Bristol Myers Squibb’s (BMS) first Cereblon E3 ligase modulator (CELMoD) therapy, ZENBEXUS™ (iberdomide), in combination with daratumumab, hyaluronidase-fihj, and dexamethasone (ZDd). This approval targets adult patients with multiple myeloma, particularly those experiencing early relapse after initial treatment. ZENBEXUS has also received Breakthrough Therapy Designation, acknowledging its innovative potential. This marks a significant advancement in expanding treatment options for relapsed/refractory multiple myeloma, providing a new class of oral therapy to this challenging patient population.

Technical / Clinical Details

ZENBEXUS (iberdomide) is a small molecule drug that targets the Cereblon (CRBN) E3 ligase, promoting the degradation of specific proteins. In multiple myeloma treatment, this mechanism is expected to inhibit cancer cell proliferation and induce apoptosis. The combination therapy with daratumumab (a CD38-targeting antibody) and dexamethasone (a steroid) leverages established standard approaches in multiple myeloma treatment, creating synergistic anti-tumor effects. This accelerated approval was based on the minimal residual disease (MRD)-negative complete response (CR) rate, a surrogate endpoint from the Phase 3 EXCALIBER-RRMM study. An MRD-negative CR indicates a deep remission of the disease and is strongly associated with improved long-term outcomes for patients.

Background & Context

Multiple myeloma is an intractable blood cancer characterized by the recurrent relapse of plasma cell cancer. Despite advancements in therapeutic options, many patients eventually develop treatment resistance, necessitating a continuous need for new therapeutic alternatives. Providing effective treatments in earlier relapse stages is particularly crucial for improving patient prognosis. CELMoD drugs offer a new therapeutic strategy against multiple myeloma cells with a distinct mechanism of action compared to conventional immunomodulatory drugs (IMiDs). The review under the FDA’s Project Orbis initiative reflects international regulatory collaboration aimed at rapidly delivering innovative cancer treatments to patients worldwide.

Strategic Significance & Outlook

The accelerated approval of ZENBEXUS holds profound significance for patients with multiple myeloma, especially those in early relapse. This drug is expected to offer new hope to patients who are resistant to existing therapies or those striving for deeper remissions. As an accelerated approval, BMS is required to provide results from confirmatory trials, which will validate the long-term clinical benefits. The success of this CELMoD therapy could further accelerate the development of targeted protein degraders in other hematological cancers and solid tumors. Moving forward, the inclusion of ZENBEXUS in multiple myeloma treatment guidelines is anticipated to allow more patients to benefit from this innovative therapeutic approach, potentially altering the treatment landscape and improving global patient outcomes.

Source: 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

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