Efficacy and Safety of Daratumumab in Intermediate/High-risk Smoldering Multiple Myeloma: Final Analysis of CENTAURUS

• Daratumumab continued to demonstrate single-agent clinical activity in patients with intermediate- or high-risk smoldering myeloma

• No new safety concerns were observed after extended follow-up of ~7 years, highlighting the tolerability of daratumumab

Early intervention of smoldering multiple myeloma (SMM) may delay progression to multiple myeloma. Here, we present the final analysis of the phase 2 CENTAURUS study (NCT02316106). In total, 123 patients with intermediate/high-risk SMM were randomized to intravenous daratumumab 16 mg/kg following a Long intense (n = 41), Intermediate (n = 41), or Short intense (n = 41) dosing schedule. At a combined median follow-up of 85.2 months, in the Long intense, Intermediate, and Short intense arms complete response or better rates were 4.9%, 9.8%, and 0%; overall response rates were 58.5%, 53.7%, and 37.5%; progressive disease/death rates were 0.096, 0.102, and 0.109 (P <0.0001 for all arms); and median progression-free survival was not reached, 84.4, and 74.1 months, respectively. Median overall survival was not reached in any arm. Thirty-six patients in the Long intense or Intermediate arms continued daratumumab in an optional extension phase after completing 20 cycles of per protocol treatment. Median (range) duration of study treatment was 44.0 (1.0-91.6), 35.2 (1.9-90.6), and 1.6 (0.1-1.9) months in the Long intense, Intermediate, and Short intense arms, respectively. No new safety signals were observed. With extended follow-up (median, ~7 years), these data highlight the tolerability of daratumumab and support ongoing trials investigating daratumumab as an early intervention for SMM. ClinicalTrials.gov Identifier: NCT02316106.