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Evaluating the Real-World Value of Daratumumab Addition to Multiple Myeloma Induction Therapy by Real-World Minimal Residual Disease Assessment and Extended Genetic Profiling.

Title: Evaluating the Real-World Value of Daratumumab Addition to Multiple Myeloma Induction Therapy by Real-World Minimal Residual Disease Assessment and Extended Genetic Profiling.
Authors: Bertuglia, G; Seneca, E; Corbett, T; Croft, J; Kaczmarek, P; Ellis, L; Neoh, C; Renaudon-Smith, E; Vanhinsbergh, L; Lindsay, J; Bonetto, S; Kristinsson, SY; Spence, D; Pratt, G; Jackson, G; Ethell, M; Nicholson, E; Messiou, C; Brown, T; Conneely, L; Thornton, T; Fuller, L; Petrizan, MV; Dunlop, A; Smith, K; Gay, F; Pawlyn, C; Boyd, KD; Kaiser, MF
Contributors: Messiou, Christina; Pawlyn, Charlotte; Kaiser, Martin
Publisher Information: CIG MEDIA GROUP, LP
Publication Year: 2026
Collection: The Institute of Cancer Research (ICR): Publications Repository
Subject Terms: Cytogenetics; Flow cytometry; Genetic markers; Outcome; Prognostication
Subject Geographic: United States
Description: BACKGROUND: Daratumumab, bortezomib, thalidomide, and dexamethasone (Dara-VTd) is the current standard of care in Europe based on the CASSIOPEIA study, which demonstrated improved depth of response and progression-free survival when daratumumab is added to VTd. PATIENTS AND METHODS: We conducted a retrospective analysis of patients treated with VTd or Dara-VTd at the Royal Marsden Hospital (RMH). Post-transplant response was assessed by biochemical response and minimal residual disease (MRD) using flow cytometry (sensitivity 10⁻⁵), with additional stratification by cytogenetic risk. RESULTS: A total of 173 patients (103 Dara-VTd, 70 VTd) with balanced baseline characteristics were included; 150 patients (87%) had a full cytogenetic panel. Median follow-up was 18.6 months. Post-transplant overall response rate was higher with Dara-VTd than VTd (97.1% vs. 87.1%), as was MRD negativity (78.6% vs. 55.7%). While Dara-VTd consistently outperformed VTd, the benefit decreased in patients with multiple high-risk cytogenetic abnormalities. Twenty-four-month progression-free survival was 97.3%, 94.1%, and 63.9% for patients with 0, 1, and ≥ 2 abnormalities treated with Dara-VTd, compared with 82.6%, 61.9%, and 55.6% for VTd, respectively. CONCLUSION: Adding daratumumab to VTd improves post-transplant response and MRD negativity in real-world practice. The magnitude of benefit diminishes with increasing numbers of high-risk cytogenetic abnormalities, supporting the value of risk-adapted strategies and real-world MRD assessment in treatment evaluation.
Document Type: article in journal/newspaper
File Description: Print-Electronic; S2152-2650(25)04284-3 -; application/pdf
Language: English
ISSN: 2152-2669; 2152-2650
Relation: S2152-2650(25)04284-3; Clinical Lymphoma, Myeloma and Leukemia, 2025, pp. S2152-2650(25)04284-3 -; https://repository.icr.ac.uk/handle/internal/7386
DOI: 10.1016/j.clml.2025.11.003
Availability: https://doi.org/10.1016/j.clml.2025.11.003; https://repository.icr.ac.uk/handle/internal/7386
Rights: http://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.F6338E5F
Database: BASE