P-083: The role of minimal residual disease evaluation for patients with multiple myeloma

Introduction: A new treatment goal for multiple myeloma (MM) is the achievement of minimal residual disease (MRD) negativity, indicating a profound response to therapy. In this study, we present the findings of MRD assessment conducted over three years at our institute, shedding light on its role in managing newly diagnosed (NDMM) or relapsed/refractory MM (RRMM).

Methods: Since 2019, the institute has initiated a minimal residual disease (MRD) evaluation using next-generation flow (NGF) technology. A minimum of 10^7 cells per sample were acquired to ensure high sensitivity. In addition, the detection limit was set at 20 cells among the total nucleated cells, enabling a sensitivity of 10^5 or higher for all samples. The initial MRD assessment (MRD1) was performed upon achieving VGPR or CR. Subsequently, the second MRD assessment (MRD2) was conducted 12 months after the initial assessment. The progression-free survival 1 (PFS1) was defined from the initiation of front-line chemotherapy until disease progression, death from any cause, or the last follow-up. The PFS2 was determined from the start of second-line chemotherapy. The overall survival (OS) was defined as the period from the commencement of front-line chemotherapy until death or the last follow-up. Statistical analyses were conducted using the IBM PASW version 25.0.

Results: MRD1 was evaluated in 138 NDMM and 60 RRMM, followed by MRD2 in 53 NDMM and 27 RRMM. The NDMM patients with MRD1-negative seemed to show superior median PFS1 to those without MRD1-negative (67.9 vs. 34.3 months, P=0.123). Although the difference was not statistically significant, patients with MRD2-negative results tended to exhibit a slightly better median PFS1 in a Kaplan-Myer graph than those without MRD2-negative results (not reached vs. not reached, P=0.258). Furthermore, the patients who achieved sustained MRD-negative or converted from MRD1-positive to MRD2-negative seemed to present better PFS than those who did not achieve final MRD2-negative (P=0.337). OS seemed superior in patients with MRD1-negative (P=0.069) but not MRD2-negative (P=0.910).
PFS2 between RRMM with MRD1-negative and MRD1-positive was not statistically different (46.0 vs. 34.9 months, P=0.169). Moreover, the patients with MRD2-negative seemed somewhat to present longer median PFS2 than those with MRD2-positive (NR vs. 35.1 months, P=0.058), but not statistically. Moreover, the RRMM patients with sequential MRD-negative or converted from MRD1-positive to MRD2-negative did not show differences in PFS2 compared to other groups (P=0.185).

Conclusions: We discussed the significance of MRD in the context of both NDMM and RRMM. While the results did not fully demonstrate the critical impact of the sequential acquisition of MRD-negativity following MRD1 due to the small number of patients in each group and short-term follow-up duration, it appeared that patients who maintained MRD-negativity had a notable survival advantage compared to those who tested positive for MRD1 or MRD2 at least once.