Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma

Area of Science:

• Hematology
• Oncology
• Clinical Trials

Background:

• Daratumumab, an anti-CD38 monoclonal antibody, is approved for multiple myeloma treatment.
• High-risk smoldering multiple myeloma (SMM) is a precursor to active disease, with no current approved treatments.
• There is a need for data on daratumumab's efficacy in high-risk SMM.

Purpose of the Study:

• To evaluate the efficacy and safety of subcutaneous daratumumab monotherapy compared to active monitoring in patients with high-risk smoldering multiple myeloma.
• To assess the impact of daratumumab on progression-free survival and overall survival.

Main Methods:

• A phase 3 randomized trial assigned patients with high-risk SMM to subcutaneous daratumumab or active monitoring.
• Treatment duration was up to 39 cycles (36 months) or until disease progression.
• The primary endpoint was progression-free survival, with progression assessed by an independent review committee.

Main Results:

• The risk of disease progression or death was 51% lower with daratumumab (HR, 0.49; P<0.001).
• Five-year progression-free survival was 63.1% with daratumumab versus 40.8% with active monitoring.
• Five-year overall survival was 93.0% with daratumumab compared to 86.9% with active monitoring; hypertension was the most common grade 3/4 adverse event.

Conclusions:

• Subcutaneous daratumumab monotherapy significantly reduces the risk of progression to active multiple myeloma or death in high-risk SMM patients.
• Daratumumab monotherapy is associated with improved overall survival compared to active monitoring.
• No new safety concerns were identified with daratumumab treatment in this patient population.