P-080: Clinical implication of MRD measurement by DuraClone in patients with transplant-eligible, real-world-based study, CAREMM-2104

Introduction: Because the DuraClone has benefits of shorter time and lower cost to generate minimal residual disease (MRD) measurement compared to EuroFlow which is regarded as standard multiparameter flow cytometry (MFC) method, we explored whether the MRD detection by DuraClone method could be reliable for real-world practice for multiple myeloma (MM).

Methods: We included 166 patients as the cohort of current study based on following inclusion criteria: (i) patients who have available MRD data at 3±2 months post-autologous stem cell transplantation (ASCT) (ii) Patient who received ASCT as a part of the front-line treatment. Fresh EDTA anticoagulated bone marrow aspirate samples were collected from treated patients with MM. Red blood cells were lysed using Versafix solution (VersaLyse supplemented with 0.25% IOTest Fixative Solution, Beckman Coulter) and cell suspensions containing 5×10^6 nucleated cells were transferred to DuraClone RE PC tubes. DuraClone RE PC antibody panel was composed of CD81-FITC, CD27-PE, CD19-PC5.5, CD200-PC7, CD138-APC, CD56-APC-A750, CD38-Pacific Blue, CD45-Krome Orange.

Results: Of 166 patients in our study, there were 113 patients (68.1%) showed MRD-negative (MRD- group) while 53 cases (31.9%) presented MRD-positivity (MRD+ group). With median follow-up of 24.4 months from ASCT, MRD+ group showed poorer survival outcomes compared to MRD- group: 24-months progression-free survival (PFS) rate, 50.6 vs. 72.3%, p< 0.001; 24-months cumulative incidence of MM progression, 46.7 vs. 26.7%, p=0.002. The multivariable analysis showed that MRD status at 3 months was significantly associated with both PFS (Hazard ratio= 2.35, p=0.008) and cumulative incidence of MM progression (Hazard ratio=2.45, p=0.004), even after adjustment for other potential factors. Of MRD- group (n=113), we further analyzed with 67 patients who have data of secondarily measured MRD after 1 year from first measurement of MRD. Patients with conversion of MRD to positivity (n = 24) showed significantly lower outcomes compared to patients achieving sustained MRD negativity (n=43): 24 months-PFS rate, 69.7 vs. 91.9%, p=0.01; 24-months cumulative incidence of MM progression, 30.3% vs. 5.7%, p=0.004. Among 53 patients of MRD+ group, A 24 months-PFS rate in patients who received no further treatment (n=11) showed significantly lower compared to that in patients with subsequent therapy (20.5 vs. 59.8%, p=0.019), we also observed a poor trend of 24 months-cumulative incidence of MM progression in patients who received no further treatment rather than in patients with subsequent therapy (69.3 vs. 40.2%, p=0.07)

Conclusions: Our data revealed that MRD measurement using DuraClone panel could be applicable with a sensitivity of 1/10^5 which value is the prerequisite by IMWG recommendation. DuraClone panel-used MRD could be a useful approach regarding both prognostic impact and predictive power for MRD-adopted treatment.