Daratumumab treatment shows promise for high-risk smoldering multiple myeloma in phase 3 trial

Mayo ClinicDec 10 2024

A new treatment is showing promise for people with high-risk smoldering multiple myeloma (SMM). This precancerous condition can progress to active multiple myeloma, a type of blood cancer. High-risk SMM carries a higher likelihood of progression.

Results from a phase 3 clinical trial, published in the New England Journal of Medicine and presented at this week's American Society of Hematology meeting, demonstrated that daratumumab, a monoclonal antibody that targets CD38, a protein found on the surface of myeloma cells, significantly reduces the risk of progression to active multiple myeloma and improves overall survival compared to active monitoring.

Smoldering multiple myeloma is a condition in which abnormal plasma cells accumulate in the bone marrow but do not display symptoms of active multiple myeloma. High-risk SMM, however, carries a significant risk of progressing to active disease. Until now, there has been no approved treatment for this high-risk group.

The multicenter, international AQUILA study randomly assigned 390 patients with high-risk SMM to receive either daratumumab or active monitoring. After a median follow-up of 65.2 months, the study demonstrated a 51% reduction in the risk of disease progression or death for those receiving daratumumab. At five years, 63.1% of patients in the daratumumab group remained progression-free, compared to 40.8% in the active monitoring group. Survival at five years was also significantly higher in the daratumumab group (93% vs. 86.9%).

These results are a major advancement in the treatment of high-risk smoldering multiple myeloma. For the first time, we have a treatment option that can significantly delay or prevent the progression to active disease, improving the lives of patients and offering them a chance at a longer, healthier future."

S. Vincent Rajkumar, M.D., hematologist, Mayo Clinic Comprehensive Cancer Center and lead investigator of the trial

While hypertension was the most common side effect, occurring in a small percentage of patients in both groups, no new safety concerns were identified with daratumumab.

"This study provides strong evidence for the use of daratumumab as a treatment for high-risk smoldering multiple myeloma," says Dr. Rajkumar, the Edward W. and Betty Knight Scripps Professor of Medicine in honor of Edward C. Rosenow III, M.D.

Patients should discuss this new treatment option with their healthcare team to determine if it is appropriate for their individual circumstances.