FDA Approves New Type of Treatment for People With Multiple Myeloma

People with multiple myeloma whose cancer has returned after treatment now have a new option. The U.S. Food and Drug Administration recently approved iberdomide (Zenbexus) in combination with daratumumab and dexamethasone, making it the first approved medicine in a new class known as CELMoDs, or cereblon E3 ligase modulators.

The treatment is approved for adults who have received at least one prior line of therapy that included a proteasome inhibitor and an immunomodulatory drug.

The approval is notable because multiple myeloma, a cancer of plasma cells in the bone marrow, often becomes more challenging to treat over time as patients cycle through different therapies.

Melissa Alsina, MD

"While outcomes for patients with multiple myeloma have improved significantly over the last two decades, most patients will eventually experience a relapse and require additional treatment," said Melissa Alsina, MD, a myeloma specialist in the Blood and Marrow Transplant and Cellular Immunotherapy Department at Moffitt Cancer Center. "The approval of iberdomide introduces a new class of therapy and expands the options available for patients whose disease has returned after prior treatment."

A New Approach to Treatment

What sets iberdomide apart is how it works.

CELMoDs are designed to harness the cell's natural protein disposal system, helping identify and eliminate proteins that myeloma cells depend on to grow and survive. Researchers believe the drugs may also help stimulate the immune system's ability to recognize and attack cancer cells.

"CELMoDs build upon decades of research into therapies that target cereblon, a protein that plays an important role in myeloma cells survival," Alsina said. "Iberdomide is a more potent cereblon modulator than immunomodulatory drugs like lenalidomide, that can degrade key proteins myeloma cells rely on to survive while also enhancing immune activity. That dual effect makes it a particularly interesting addition to our treatment arsenal."

The approval marks the first time a CELMoD has become available to patients with multiple myeloma, opening the door to a new category of therapy for the disease.

Results From a Phase 3 Study

The FDA's decision was based on results from the phase 3 EXCALIBER-RRMM clinical trial, which evaluated the iberdomide combination in patients with relapsed or refractory multiple myeloma.

Patients who received the iberdomide regimen achieved deeper responses to treatment than those receiving a standard therapy. In the study, 41% of patients receiving the iberdomide combination achieved a complete response with no detectable evidence of disease, compared with 21% of patients receiving standard treatment.

The findings supported the FDA's accelerated approval of the drug. Additional studies are underway to further evaluate long-term outcomes, including disease progression and survival.

Iberdomide is taken orally as part of a three-drug regimen that also includes daratumumab and dexamethasone.

"Every new treatment class gives us another opportunity to personalize therapy and sequence treatments more effectively over the course of a patient's disease," Alsina said. "For patients whose myeloma has returned, having access to a new mechanism of action is important because it gives us another way to target the disease, particularly when resistance to prior therapies develops. Other studies are currently evaluating the efficacy of iberdomide in other disease states, like newly diagnosed myeloma and maintenance.