BACKGROUND: Daratumumab, an anti-CD38 monoclonal antibody, has been approved for the treatment of multiple myeloma. Data are needed regarding the use of daratumumab for high-risk smoldering multiple myeloma, a precursor disease of active multiple myeloma for which no treatments have been approved. METHODS: In this phase 3 trial, we randomly assigned patients with high-risk smoldering multiple myeloma to receive either subcutaneous daratumumab monotherapy or active monitoring. Treatment was continued for 39 cycles, for 36 months, or until confirmation of disease progression, whichever occurred first. The primary end point was progression-free survival; progression to active multiple myeloma was assessed by an independent review committee in accordance with International Myeloma Working Group diagnostic criteria. RESULTS: Among the 390 enrolled patients, 194 were assigned to the daratumumab group and 196 to the active-monitoring group. With a median follow-up of 65.2 months, the risk of disease progression or death was 51% lower with daratumumab than with active monitoring (hazard ratio, 0.49; 95% confidence interval [CI], 0.36 to 0.67; P<0.001). Progression-free survival at 5 years was 63.1% with daratumumab and 40.8% with active monitoring. A total of 15 patients (7.7%) in the daratumumab group and 26 patients (13.3%) in the active-monitoring group died (hazard ratio, 0.52; 95% CI, 0.27 to 0.98). Overall survival at 5 years was 93.0% with daratumumab and 86.9% with active monitoring. The most common grade 3 or 4 adverse event was hypertension, which occurred in 5.7% and 4.6% of the patients in the daratumumab group and the active-monitoring group, respectively. Adverse events led to treatment discontinuation in 5.7% of the patients in the daratumumab group, and no new safety concerns were identified. CONCLUSIONS: Among patients with high-risk smoldering multiple myeloma, subcutaneous daratumumab monotherapy was associated with a significantly lower risk of progression to active multiple myeloma or death and with higher overall survival than active monitoring. No unexpected safety concerns were identified. (Funded by Janssen Research and Development; AQUILA ClinicalTrials.gov number, NCT03301220.).

Albert Schweitzer Hospital Dordrecht the Netherlands

Alexandra General Hospital National and Kapodistrian University of Athens Athens

Ankara University Ankara Turkey

Charles University and General Hospital Prague Czech Republic

Clínica Medica São Germano São Paulo

Cross Cancer Institute University of Alberta Edmonton Canada

Genmab US Plainsboro NJ

GMMG Study Group at University Hospital Heidelberg Internal Medicine 5 Heidelberg Germany

Hospital Alemán Buenos Aires

Institut Català d'Oncologia and Institut Josep Carreras Hospital Germans Trias i Pujol Barcelona

Institute of Hematology and Transfusion Medicine Warsaw Poland

Janssen Research and Development Beerse Belgium

Janssen Research and Development Raritan NJ

Janssen Research and Development Shanghai China

Janssen Research and Development Spring House PA

Janssen Scientific Affairs Horsham PA

Japanese Red Cross Medical Center Tokyo

Jessa Hospital Hasselt Belgium

Kent and Canterbury Hospital Canterbury United Kingdom

Knight Cancer Institute Oregon Health and Science University Portland

Levine Cancer Institute Atrium Health Wake Forest University School of Medicine Charlotte NC

Mayo Clinic Rochester MN

Medical Unit Hematology Karolinska University Hospital Stockholm

Ogaki Municipal Hospital Ogaki City Japan

Oslo Myeloma Center Department of Hematology Oslo University Hospital Oslo

Perth Blood Institute Murdoch University Perth WA Australia

Rigshospitalet University of Copenhagen Copenhagen

South Pest Central Hospital National Institute for Hematology and Infectious Diseases Budapest Hungary

SSD Clinical Trials in Oncol ematologia e Mieloma Multiplo AOU Città della Salute e della Scienza di Torino Turin Italy

Tel Aviv Sourasky Medical Center and Tel Aviv University Tel Aviv Israel

University Hospital Hôtel Dieu Nantes France

University Hospital of Salamanca IBSAL and Cancer Research Center IBMCC Salamanca Spain

University of Washington and Fred Hutchinson Cancer Center Seattle

Washington University School of Medicine St Louis

References provided by Crossref.org

EHA-EMN Evidence-Based Guidelines for diagnosis, treatment and follow-up of patients with multiple myeloma

See more in PubMed

ClinicalTrials.gov
NCT03301220