Testing A New Drug Combination For Relapsed/Refractory Multiple Myeloma

Mezigdomide is a new immunomodulatory agent in a novel therapeutic family called CELMoDs (Cereblon E3 ligase modulatory drugs). It could be considered the “next generation” drug to pomalidomide and lenalidomide. 

These CELMoDs are primarily being used as a treatment for people with myeloma who progressed or stopped responding to treatment with lenalidomide or pomalidomide. 

In the following interview, Dr. Luciano Costa from the University of Alabama-Birmingham shares details about the CA057-003 trial, in which mezigdomide (MEZI), tazemetostat (TAZ), and dexamethasone (dex) are combined to treat relapsed/refractory multiple myeloma patients. 

MEZI is a new type of drug designed to fight cancer cells more effectively than older drugs like lenalidomide and pomalidomide. It destroys certain proteins in cancer cells, making them die off faster. This also helps your immune system recognize and attack the cancer more efficiently. 

TAZ is another drug that specifically targets a problem area in the cancer cells, known as the PRC2 complex, which is often dysregulated in certain cancers like multiple myeloma. If PRC2 remains dysregulated, it may turn off genes that normally prevent uncontrolled cell growth, making drugs like TAZ crucial for cancer cell suppression. 

When MEZI and TAZ work together, they attack the cancer from different angles, making the treatment more powerful. Dexamethasone helps synergize and strengthen the combination. 

You can watch the video here and learn more from the interview below. 

Study Details

This was a Phase 1 and 2 Clinical Trial (NCT05372354). Its primary purpose was to establish a recommended dose of the combination therapy, determine dosing schedules, and evaluate safety (identify side effects and their severity). 

12 patients were treated in this study. Their median age was 68 years old. Although a small sample size, this group represented a hard-to-treat population because of the following details: 

• Many of these patients had myeloma in pockets of the body outside of the blood and bone marrow (extramedullary disease).
• More than half had received T-cell redirecting therapy.
• All had relapsed or refractory disease, with 83.3% being triple-class refractory (unresponsive to three different categories of treatment).

Study Results

The overall response rate (ORR) was 60%, including one stringent complete response (sCR), two very good partial responses (VGPR), and three partial responses (PR).

It took patients around 1.8 months to start responding to the treatment. 

66.7% of patients experienced serious side effects, with neutropenia (low neutrophil/white cell blood count) and anemia (low red cell blood count) being the most common hematologic side effects. Infections also occurred in 16.7% of patients. 

There were no dose-limiting toxicities or treatment-related deaths. Patients were given the highest dose of the combination without any significant changes to the side effect profile, which is significant because that means a more potent treatment doesn’t lower the quality of life of the person receiving it. 

Conclusion

This study showed successful efficacy and tolerability of the combination treatment options of mezigdomide (MEZI), tazemetostat (TAZ), and dexamethasone in people with heavily pre-treated multiple myeloma.

This is proving to be an effective, all-oral therapy for relapsed/refractory multiple myeloma patients who have previously received multiple unsuccessful lines of treatment. We look forward to more clinical trial data in a Phase III trial. 

If you want to learn more about multiple myeloma treatment advances, read our news articles on the subject here: Myeloma Treatment Advances 

Sources: 

• MEZIGDOMIDE (MEZI), TAZEMETOSTAT (TAZ), AND DEXAMETHASONE(DEX) IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA(RRMM): PRELIMINARY RESULTS FROM THE CA057-003 TRIAL