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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

Lookup NU author(s): Professor Graham Jackson

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Abstract

© 2025 The Author(s)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.

Publication metadata

Author(s): 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

Publication type: Article

Publication status: Published

Journal: Clinical Lymphoma, Myeloma and Leukemia

Year: 2025

Pages: epub ahead of print

Online publication date: 10/11/2025

Acceptance date: 05/11/2025

ISSN (print): 2152-2650

ISSN (electronic): 2152-2669

Publisher: Elsevier Inc.

URL: https://doi.org/10.1016/j.clml.2025.11.003

DOI: 10.1016/j.clml.2025.11.003

PubMed id: 41318255

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