Bristol Myers Squibb’s Molecular Glue Mezigdomide Shows Promising Clinical Data in Heavily Pretreated Multiple Myeloma, Published in The New England Journal of Medicine

▎WuXi

Edited by Kant Content Team

Recently, the phase 1/2 clinical trial data of mezigdomide, an investigational molecular glue developed by Bristol-Myers Squibb, was published in The New England Journal of Medicine. The results showed,In heavily pretreated multiple myeloma (MM) patients, the all-oral combination therapy of mezigdomide plus dexamethasone demonstrated favorable efficacy.

Multiple Myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow. In multiple myeloma, these plasma cells undergo changes, spread rapidly, and form tumors that replace normal cells in the bone marrow. Multiple myeloma is the third most common blood cancer, with a 5-year relative survival rate of 59.8% for patients. While some individuals diagnosed with multiple myeloma may initially have no symptoms, most patients present with symptoms that can include fractures or pain, low red blood cell count, fatigue, high calcium levels, and kidney problems or infections.

Mezigdomide is a novel E3 ubiquitin ligase cereblon modulator with potent anti-proliferative and tumoricidal activity in preclinical models of multiple myeloma, including tumor models resistant to lenalidomide and pomalidomide.

In this phase 1-2 trial, patients with relapsed and refractory myeloma received oral mezigdomide combined with dexamethasone.

In the phase 1 trial, a total of 77 patients were enrolled. The most common dose-limiting toxicities were neutropenia and febrile neutropenia.Based on the phase 1 study results, the researchers determined that the recommended phase 2 trial dose of mezigdomide is 1.0 mg, administered once daily in combination with dexamethasone for 21 days, followed by a 7-day rest period.。

In the phase 2 trial, a total of 101 patients received the recommended dose on the same schedule. All patients in the dose-expansion cohort had triple-class–refractory multiple myeloma (including immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies), with 30 patients (30%) having previously received treatment targeting B-cell maturation antigen (BCMA) and 40 patients (40%) having plasmacytoma.

The analysis shows,The overall response rate was 41% (95% CI: 31-51), with a median duration of response of 7.6 months (95% CI: 5.4-9.5; data not yet mature), a median progression-free survival of 4.4 months (95% CI: 3.0-5.5), and a median follow-up of 7.5 months (0.5-21.9).The most common adverse events (almost all of which were confirmed to be reversible) included neutropenia (77%) and infection (65%; Grade 3, 29%; Grade 4, 6%). Treatment-related adverse events mainly consisted of bone marrow toxicity, and no unexpected toxicities were observed.

The author of the paper believes that,This result shows that the all-oral combination therapy of mezigdomide plus dexamethasone demonstrates good efficacy in heavily pretreated multiple myeloma patients.。