Daratumumab or active monitoring for high-risk smoldering multiple myeloma

Among patients with smoldering multiple myeloma at high risk for progression, progression-free survival at 5 years was 63.1% with daratumumab monotherapy, as compared with 40.8% with active monitoring.

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Bibliographic Details
Main Authors:	Dimopoulos, Meletios A. (Author) , Voorhees, Peter M. (Author) , Schjesvold, Fredrik (Author) , Cohen, Yael C. (Author) , Hungria, Vania (Author) , Sandhu, Irwindeep (Author) , Lindsay, Jindriska (Author) , Baker, Ross I. (Author) , Suzuki, Kenshi (Author) , Kosugi, Hiroshi (Author) , Levin, Mark-David (Author) , Beksac, Meral (Author) , Stockerl-Goldstein, Keith (Author) , Oriol, Albert (Author) , Mikala, Gabor (Author) , Garate, Gonzalo (Author) , Theunissen, Koen (Author) , Spicka, Ivan (Author) , Mylin, Anne K. (Author) , Bringhen, Sara (Author) , Uttervall, Katarina (Author) , Pula, Bartosz (Author) , Medvedova, Eva (Author) , Cowan, Andrew J. (Author) , Moreau, Philippe (Author) , Mateos, Maria-Victoria (Author) , Goldschmidt, Hartmut (Author) , Ahmadi, Tahamtan (Author) , Sha, Linlin (Author) , Cortoos, Annelore (Author) , Katz, Eva G. (Author) , Rousseau, Els (Author) , Li, Liang (Author) , Dennis, Robyn M. (Author) , Carson, Robin (Author) , Rajkumar, S. Vincent (Author)
Format:	Article (Journal)
Language:	English
Published:	May 8, 2025
In:	The New England journal of medicine Year: 2025, Volume: 392, Issue: 18, Pages: 1777-1788
ISSN:	1533-4406
DOI:	10.1056/NEJMoa2409029
Online Access:	Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1056/NEJMoa2409029 Verlag, lizenzpflichtig, Volltext: https://www.nejm.org/doi/full/10.1056/NEJMoa2409029
Author Notes:	M.A. Dimopoulos, P.M. Voorhees, F. Schjesvold, Y.C. Cohen, V. Hungria, I. Sandhu, J. Lindsay, R.I. Baker, K. Suzuki, H. Kosugi, M.-D. Levin, M. Beksac, K. Stockerl‑Goldstein, A. Oriol, G. Mikala, G. Garate, K. Theunissen, I. Spicka, A.K. Mylin, S. Bringhen, K. Uttervall, B. Pula, E. Medvedova, A.J. Cowan, P. Moreau, M.-V. Mateos, H. Goldschmidt, T. Ahmadi, L. Sha, A. Cortoos, E.G. Katz, E. Rousseau, L. Li, R.M. Dennis, R. Carson, and S.V. Rajkumar, for the AQUILA Investigators

Description
Summary:	Among patients with smoldering multiple myeloma at high risk for progression, progression-free survival at 5 years was 63.1% with daratumumab monotherapy, as compared with 40.8% with active monitoring. 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.)
Item Description:	Veröffentlicht: 09. Dezember 2024 Gesehen am 28.11.2025
Physical Description:	Online Resource
ISSN:	1533-4406
DOI:	10.1056/NEJMoa2409029