Associate Professor University Hospital Ostrava and University of Ostrava, Ostrava, Czech Republic, Czech Republic
Introduction: Minimal residual disease (MRD) is a sensitive measure of tumor plasma cells in the bone marrow that reflects remission status. The strong prognostic value of MRD negativity which may act as clinically valid surrogate biomarker for progression-free (PFS) and overall survival (OS) in multiple myeloma (MM) has been demonstrated in many clinical trials including meta-analysis (Munshi et al., Blood Advances, 2020). However, large and reliable data with long follow-up from real-world practice are still missing.
Methods: Newly diagnosed transplant eligible MM patients (pts) who reached at least partial response (PR) on Day +100 (D+100) after autologous stem cell transplantation (ASCT) underwent MRD assessment of the bone marrow using multiparameter flow cytometry (MFC) with sensitivity reaching at least to 10e-5. Patients were treated in the real-world (RW) setting and clinical analysis was performed retrospectively based on data from the Czech Registry of Monoclonal Gammopathies (RMG, https://rmg.healthregistry.org/). Median PFS and OS intervals were calculated since MRD evaluation.
Results: In total, 342 MM pts treated across 6 Czech hematological centers between 2014 and 2022 underwent MRD assessment on D+100 after ASCT using MFC. The most common induction regimen was VTD (bortezomib, thalidomide, dexamethasone) in 70% of pts, the median limit of detection of MFC technique was 0.001%, and the median follow-up was 30.2 months. Overall, 158 (46%) of 342 pts were considered MRD negative which was associated with significantly improved PFS (HR=0.37; 95% CI 0.26 – 0.52; p< 0.001) and OS (HR=0.49; 95% CI 0.3 – 0.81; p=0.004). Median PFS was 49.2 months for pts who were MRD negative vs. 19.0 months for MRD positive pts; median OS was not reached vs. 71.9 months, respectively. In subgroup analysis, MRD negativity was associated with prolonged survival in both high-risk and standard-risk pts by cytogenetics as well as in patients reaching complete remission or better (CR or better) and very good partial response or better (VGPR or better). Finally, in multivariate analysis only MRD positivity and high-risk cytogenetics emerged as independent adverse prognostic factors (HR=2.57; p< 0.001).
Conclusions: Up to our knowledge, this is the largest real-world study confirming the strong prognostic value of MRD negativity assessed by MFC with median limit of detection to 10e-5 in newly diagnosed transplant-eligible MM. MRD negativity was associated with improved PFS (HR=0.37) and OS (HR=0.49) resembling the results from clinical trials setting. This real-world experience might represent the missing piece of evidence for final approval of MRD as a surrogate for PFS and OS by regulatory authorities.
