Mezigdomide - a CELMoD in Clinical Trials

What Is Mezigdomide?

Mezigdomide is a CELMoD agent that is being studied in many clinical trials with different drug combinations and in different myeloma patient populations.

What Are CELMoDs?

Cereblon (CRBN) E3 ligase modulators (CELMoDs) are a new drug class in myeloma. The emergence of CELMoDs is building on the well-established platform of immunomodulatory agents. CELMoDs are oral (taken by mouth) medications that have many similarities to immunomodulatory agents. Yet, CELMoDs can be used even in patients who have relapsed after treatment with immunomodulatory agents.

How Is Mezigdomide Used in Multiple Myeloma?

While still in clinical trials, mezigdomide has demonstrated some positive results. Combination therapy with mezigdomide and dexamethasone (also called “MEZI-dex”) has also shown to be very effective in patients with at least 3 prior lines of therapy. This includes some patients who have been treated with a B-cell maturation antigen (BCMA)-directed therapy. The overall response rates (ORRs) have been mostly in the 40% to 50% range. Note: A line of therapy is 1 or more complete. Cycles of a treatment regimen that can consist of a single agent, a combination of several drugs, or a planned sequential therapy of various regimens.

Mezigdomide has also been tested in combination with other agents earlier in the disease course, especially with proteasome inhibitors in patients who have had at least one prior line of therapy. ORR data were very encouraging, from 60% to 80%.

Also, results from the CC-92480-MM-002 clinical trial of mezigdomide and dexamethasone in combination with either Darzalex or Empliciti showed promising efficacy and a manageable safety profile in patients with

• relapsed or refractory myeloma and
• 2 to 4 prior lines of therapy.

By making schedule and dose adjustments, safety and efficacy can be improved.

How Is Mezigdomide Administered?

Mezigdomide is taken by mouth. It can be combined with other myeloma therapies, such as proteasome inhibitors and monoclonal antibodies.

What Are Potential Side Effects of Mezigdomide?

A side effect, also called an adverse event (AE), is an unwanted or unexpected effect caused by a drug. Key risks of mezigdomide include the following:

• Low blood counts (especially neutrophils). This increases the risk of infection.
• Blood clots. Patients taking iberdomide should be given medication to prevent blood clots.

Patients may also experience low-grade fatigue and diarrhea. The risk of peripheral neuropathy and cardiac complications is low.

Mezigdomide has been shown to be associated with cytopenias, including:

• Grade 3 or 4 neutropenia,
• thrombocytopenia, or
• anemia.

Non-hematologic side effects included the following:

• infections
• Grade 3 insomnia
• Grade 3 gastrointestinal (GI) events such as diarrhea