The New England Journal of MedicineMezigdomide plus Dexamethasone in Relapsed and Refractory Multiple Myeloma

Mezigdomide’s Promising Efficacy in Heavily Pretreated Patients

The landscape of multiple myeloma treatment may be changing with the introduction of mezigdomide, a novel cereblon E3 ubiquitin ligase modulator. This phase 1-2 study aimed to evaluate its safety, pharmacokinetics, and efficacy when used in combination with dexamethasone in patients with relapsed and refractory multiple myeloma.

HCN Medical Memo
Physicians should consider the potential of mezigdomide, in combination with dexamethasone, as a future option for patients with relapsed and refractory multiple myeloma, especially those who have failed previous treatments. The study reports a 41% overall response rate with manageable myelotoxic side effects, making it a promising avenue in the future for heavily pretreated patients.

Study Design:

• Phase 1: 77 patients were administered oral mezigdomide combined with dexamethasone. The study aimed to assess safety and pharmacokinetics and to determine the dose and schedule for Phase 2.
• Phase 2: 101 patients received mezigdomide at the Phase 1 determined dose, focusing on overall response, safety, and efficacy. All of these patients had triple-class–refractory multiple myeloma.

Key Findings:

• Dose-Limiting Toxic Effects: Most common were neutropenia and febrile neutropenia.
• Recommended Phase 2 Dose: 1.0 mg of mezigdomide, daily, in combination with dexamethasone for 21 days, then 7 days off.
• Adverse Events: Neutropenia in 77%, and infections in 65% of patients (grade 3: 29%, grade 4: 6%).
• Overall Response: 41% of patients had partial response or better.
• Duration of Response: Median was 7.6 months.
• Progression-Free Survival: Median was 4.4 months with a median follow-up of 7.5 months.

Approximately 1 in 132 people will be diagnosed with multiple myeloma in their lifetime.

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