The Food and Drug Administration (FDA) has granted approval to three new drugs for the treatment of multiple myeloma that has relapsed following previous therapies. These approvals mark a significant advancement in the treatment landscape for this challenging cancer.
On November 16, the FDA approved daratumumab (Darzalex®) for patients who have received at least three prior lines of treatment. Daratumumab's approval was based on two single-arm trials demonstrating complete or partial tumor reduction in 29% and 36% of patients, respectively. The median duration of response was 7.4 months in the first trial.
Oral Proteasome Inhibitor Approved
On November 20, ixazomib (Ninlaro®), an oral proteasome inhibitor, was approved for patients with relapsed multiple myeloma who have received at least one prior treatment. A randomized clinical trial involving 722 patients showed that ixazomib, when combined with lenalidomide and dexamethasone, significantly improved median progression-free survival compared to lenalidomide and dexamethasone alone (20.6 months vs. 14.7 months).
Elotuzumab Extends Progression-Free Survival
On November 30, elotuzumab (Empliciti®) was approved for patients who have received one to three prior therapies. The approval was based on a randomized clinical trial of 646 participants whose myeloma did not respond to or had relapsed after previous treatment. Patients treated with elotuzumab in combination with lenalidomide and dexamethasone had a longer median progression-free survival than patients who received only lenalidomide and dexamethasone: 19.4 months versus 14.9 months.
Clinical Significance
According to Mark Roschewski, M.D., of the Lymphoid Malignancies Branch in NCI’s Center for Cancer Research, relapse is almost universal with myeloma. While some patients experience long remissions after initial treatment, very few are cured. These new approvals offer additional options for patients with relapsed disease.
"The most exciting of the three drugs is daratumumab, because it showed single-agent activity," Dr. Roschewski said. "It is not, by itself, going to cure multiple myeloma, and the duration of remission is relatively short, but it certainly provides some meaningful benefit, particularly if a patient doesn’t have any other treatment options."
Safety and Side Effects
Common side effects associated with these drugs include fatigue, diarrhea, peripheral neuropathy, and fever. Daratumumab may also cause a decrease in white blood cells. Elotuzumab and daratumumab, both monoclonal antibodies, target proteins on myeloma cells that have yet to be part of other FDA-approved therapies for this cancer type.
Future Directions
"Any time you can get three new medicines in your armamentarium, that opens up many new research opportunities that now need to be explored," Dr. Roschewski concluded. The introduction of these therapies opens avenues for further research and combination strategies to improve outcomes for patients with multiple myeloma.
