Daratumumab Active, Tolerable for Patients With Smoldering MM

In a phase 2 study of patients with intermediate- or high-risk smoldering multiple myeloma (SMM), daratumumab therapy was active and demonstrated acceptable tolerability (Leukemia. 2020 Feb 5. Epub ahead of print).

“Current guidelines for…SMM…recommend active monitoring until the onset of multiple myeloma (MM) before initiating treatment or enrollment in a clinical trial. Earlier intervention may delay progression to MM,” explained C. Ola Landgren, MD, PhD, Department of Medicine, Myeloma Service, Memorial Sloan Kettering Cancer Center, New York, and colleagues.

In the CENTAURUS clinical trial, Dr Landgren et al randomized 123 patients with intermediate- or high-risk SMM to receive intravenous daratumumab 16 mg/kg as part of an extended intense (intense), extended intermediate (intermediate), or short dosing schedule.

The co-primary end points of the study included complete response (CR) rate and progressive disease (PD)/death rate per patient-year. 

After a median follow-up of 15.8 months, the CR rates for intense, intermediate, and short dosing were 2.4%, 4.9%, and 0%, respectively. The PD/death rates for intense, intermediate, and short dosing were 0.055 (80% CI, 0.014-0.096), 0.102 (80% CI, 0.044-0.160), and 0.206 (80% CI, 0.118-0.295), respectively.

According to Dr Landgren and co-investigators, these results translated to a median progression-free survival of ≥24 months in all arms (P < .0001, P < .0001, and P = .0213, respectively).

After a longer median follow-up of 25.9 months, CR rates were 4.9%, 9.8%, and 0% for intense, intermediate, and short dosing, respectively, and PD/death rates for were 0.059 (80% CI, 0.025-0.092), 0.107 (80% CI, 0.058-0.155), and 0.150 (80% CI, 0.089-0.211), respectively.

These results also translated to a median PFS ≥24 months in all arms according to the investigators (P <.0001 for all arms).

At 24 months, the PFS rates were 89.9% (90% CI, 78.5-95.4%), 82.0% (90% CI, 69.0-89.9%), and 75.3% (90% CI, 61.1-85.0%) for intense, intermediate, and short dosing, respectively.

In most patients, intense dosing sustained target-saturating trough throughout dosing periods that were weekly, every 2 weeks, and every 4 weeks, according to pharmacokinetic analyses. There were no new safety signals observed.

“In conclusion, the findings of this study suggest that daratumumab has single-agent activity and demonstrates acceptable tolerability in intermediate-risk and high-risk SMM,” Dr Landgren and colleagues concluded.—Hina Porcelli