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Dose-Expansion Results of Mezigdomide-Based Therapy for Advanced Multiple Myeloma

By: Vanessa A. Carter, BS
Posted: Tuesday, January 24, 2023

The phase I/II CC-92480-MM-001 trial, performed by Paul G. Richardson, MD, of Dana-Farber Cancer Institute, Boston, and colleagues, evaluated mezigdomide—a novel cereblon E3 ligase modulator—combined with dexamethasone in patients with relapsed or refractory multiple myeloma. The dose-expansion results of this trial, which indicated this regimen demonstrated manageable safety and “promising” efficacy in this population, were presented during the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 568).

The study authors focused on 101 patients with relapsed or refractory multiple myeloma who had received more than three prior therapy lines or experienced disease progression within 60 days of their last therapy. Participants were administered 1 mg of oral mezigdomide on days 1 to 21 of each 28-day cycle, plus weekly doses of 20 mg or 40 mg of dexamethasone, depending on their age. The median number of prior therapies was six, with all patients’ disease refractory to their last myeloma regimen and triple-class–refractory to an immunomodulatory drug, proteasome inhibitor, and anti-CD38 monoclonal antibody.

At the median follow-up of 5.8 months, 23 patients remained on treatment. The overall response rate was 39.6%, which included 18 very good partial responses, 17 partial responses, 3 complete responses, and 2 stringent complete responses.

With 90 patients experiencing treatment-emergent adverse events, the most common grade 3 or 4 hematologic events were neutropenia (74.3%), anemia (32.7%), and thrombocytopenia (25.7%). Infections of grade 3 or 4, such as pneumonia (9.9%) and COVID-19 (5.0%), were reported in 32.7% of patients; the frequency of other grade 3 or 4 nonhematologic events was low. Dose interruptions and reductions of mezigdomide because of treatment-emergent adverse events were observed in 71.3% and 28.7% of participants, respectively. Consequently, mezigdomide therapy was discontinued in six patients.

Disclosure: For full disclosures of the study authors, visit ash.confex.com.


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