Evaluating the real-world value of Daratumumab addition to multiple myeloma induction therapy by real-world minimal residual disease assessment and extended genetic profiling.

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.

Citation

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. Evaluating the Real-World Value of Daratumumab Addition to Multiple Myeloma Induction Therapy by Real-World Minimal Residual Disease Assessment and Extended Genetic Profiling. Clin Lymphoma Myeloma Leuk. 2025 Nov 10:S2152-2650(25)04284-3. doi: 10.1016/j.clml.2025.11.003.

Type

Article