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.