P-196: B-Cell Profile in Bone Marrow and Peripheral Blood of Multiple Myeloma Patients After Autologous Stem Cell Transplantation

Introduction: Multiple myeloma (MM) is a clonal plasma cell (cPC) malignancy associated with an impairment of the B cell compartment. Previously, B-cell recovery during therapy has been reported as a prognostic factor in MM and a unique feature of MM patients who attain long-term disease control. The kinetics of B-cell reconstitution in bone marrow (BM) from MM patients during treatment was described. Still, detailed recovery of peripheral blood (PB) B-cell subsets after therapy remains to be investigated. This study aimed to describe B-cell subsets in PB vs. BM of MM patients at D+100 after autologous stem cell transplantation (ASCT) and their potential relationship with minimal residual disease (MRD).

Methods: A total of 152 paired BM and PB samples were studied from 76 MM patients – 54% males; median age of 61 y (40-70 y) – collected at D+100 post-ASCT. All patients received induction triplet regimens, including immunomodulatory drugs and/or proteasome inhibitors, followed by high-dose melphalan before ASCT. Age-matched healthy donors (HD) were studied as controls. Samples were obtained at two different centers (UFRJ, n= 88; USAL, n= 64) and analyzed by flow cytometry stained with EuroFlow NGF MM MRD two-8 color antibody combinations.

Results: BM clonal PC (MRD+) was detected in 50/76 (66%) of MM patients, and 7/50 (14%) also presented circulating tumor plasma cells (CTPC+) in PB. All MM BM samples presented B-cell precursors (BCPs) percentage above normal levels, while memory B-cells and normal PC (nPC) were under average percentage (vs. HD). MRD+CTPC+ patients had significantly lower frequencies of nPC CD19- (long-lived plasma cells) on BM compared to MRD+or- patients. In PB, memory B-cell counts were significantly reduced in all groups of MM patients vs. normal. PB nPC CD19+ (plasmablasts) significantly decreased in CTPC+ patients compared to other MM patients (MRD+ and MRD-), which reached average counts. From 38% (29/76) relapsed MM patients, 72% (21/29) were MRD+ compared to 62% (29/47) of MRD+ in non-relapsed ones. Among MRD+ patients, 14% (4/29) of the relapsed group had CTPC+ vs. 6% (3/47) of non-relapsed patients. MRD+CTPC+ patients had a significantly shorter PFS, being 9m vs. 28m in MRD+CTPC- and not reached in MRD-CTPC- patients (p=0.02). Overall, mortality was 14% (11/76), being 8/11 (72%) of MRD+ (6 CTPC- and 2 CTPC+) and 3/11 (27%) in MRD-CTPC- cases. Overall survival was 18m in MRD+CTPC+, 36m in MRD+CTPC- and 50m in MRD-CTPC- patients.

Conclusions: The presence of CTPC at D+100 post-ASCT was associated with lower recovery of nPC PB counts and worse PFS. Such findings reinforce that CTPC clearance post-ASCT would increase the availability of BM niches for nPC and potentially for BCPs, leading to normal B cell maturation recovery. Further studies with larger cohorts and longer follow-up times are necessary to understand better the effects of B cell recovery on MM survival.