Mezigdomide and Dexamethasone Combination Demonstrates Promising Efficacy for Patients With R/R Multiple Myeloma

A Phase 1/2 Study

The administration of mezigdomide plus dexamethasone in an oral combination demonstrated promising efficacy among patients with heavily pretreated, relapsed/refractory (R/R) multiple myeloma (MM), according to a phase 1/2 study. 

Paul G Richardson, MD, Dana–Farber Cancer Institute, Boston, Massachusetts, and coauthors stated, “Mezigdomide is a novel cereblon E3 ubiquitin ligase modulator with potent antiproliferative and tumoricidal activity in preclinical models of multiple myeloma, including those resistant to lenalidomide and pomalidomide.” 

To explore the efficacy of this treatment, oral mezigdomide in combination with dexamethasone was administered to patients with R/R MM in a phase 1/2 trial. The primary objectives of the phase 1, dose-escalation cohort were the evaluation of the safety and pharmacokinetics, as well as for the investigators to identify the dose and schedule for phase 2. In the phase 2, dose-expansion cohort, the objectives included the assessment of the overall response (partial response or better), safety, and efficacy of mezigdomide plus dexamethasone at the dose and schedule previously determined in the phase 1 findings.

The study’s phase 1 included 77 patients. The most common dose-limiting toxic effects were neutropenia and febrile neutropenia. Through analysis of the phase 1 findings, investigators determined the recommended phase 2 dose of mezigdomide to be 1.0 mg, administered once daily in combination with dexamethasone for 21 days, followed by 7 days off, in each 28-day cycle. 

In phase 2, 101 patients received the dose identified in phase 1 in the same schedule as identified. All patients in the dose-expansion cohort had triple-class–refractory multiple myeloma. Investigators noted that 30% of patients in this cohort had received previous anti–B-cell maturation antigen (anti-BCMA) therapy, and 40% had plasmacytomas. Study authors noted that an overall response occurred in 41% of the patients (95% confidence interval [CI], 31 to 51). The median duration of response was 7.6 months (95% CI, 5.4 to 9.5; data not yet mature), and the median progression-free survival was 4.4 months (95% CI, 3.0 to 5.5), with a median follow-up of 7.5 months, at a range of 0.5 to 21.9.

As for adverse events, the most prevalent included neutropenia in 77% of the patients and infection in 65%. No unexpected toxic effects were encountered, and almost all of the observed adverse events proved to be reversible, according to study authors. 

“The all-oral combination of mezigdomide plus dexamethasone showed promising efficacy in patients with heavily pretreated multiple myeloma, with treatment-related adverse events consisting mainly of myelotoxic effects,” concluded Dr Richardson and colleagues. 

Source:

Richardson P G, Trudel S, Popat R, et al. Mezigdomide plus dexamethasone in relapsed and refractory multiple myeloma. N Eng J Med. Published online September 14, 2023. doi: 10.1056/nejmoa2303194