P-239: The burden of circulating tumor plasma cells is associated with the quantity of mesenchymal stromal cells and CXCR4-expressing plasma cells in bone marrow of newly diagnosed multiple myeloma.

Introduction: Bone marrow mesenchymal stromal cells (BMMSC) are known to influence the homing, survival, proliferation, and exit of tumor plasma cells (TPC) in plasma cell neoplasms (PCN) including multiple myeloma (MM). The dynamic interaction between CXCR4 expressed on bone marrow TPC (BMTPC) and its ligand CXCL12, secreted by the BMMSC, is important for homing followed by egress of plasma cells into the peripheral blood circulation. The load of circulating TPC (CTPC) at the time of diagnosis is likely to be associated with quantity of CXCR4-expressing-BMTPC (CXCR4⁺BMTPC) and BMMSC in patients with newly diagnosed MM (NDMM).

Methods: The study prospectively enrolled NDMM-patients over a duration of one year. Multicolour flow cytometry (MFC) was used to quantify CTPC from 6ml EDTA-anticoagulated peripheral blood, and percentages of BMMSC & CXCR4⁺BMTPC from bone marrow aspirate sample. CTPC were enumerated using CD19, CD27, CD38, CD45, CD56, CD81, CD117/CD200, CD138, and cytoplasmic-kappa & lambda expression. BMMSC were gated based on CD105, CD73, CD90, and CD271 expression with negativity for CD45 and lineage-markers. The samples were processed & acquired on Navios-Ex flow cytometer and analyzed using Kaluza 2.2 software (Beckman Coulter, USA). The percentage of CTPC, and the percentages of BMMSC & CXCR4⁺BMTPC were statistically analyzed to evaluate their association with each other.

Results: Sixty-six patients of NDMM were enrolled. The median % of CTPC was 0.0345 (IQR 0.0016 to 0.3)%. The median BMMSC and CXCR4⁺BMTPC were 0.0034 (IQR 0.0015 to 0.01248)% and 84.87 (IQR 55.54 to 95.16)%, respectively. There was a trend toward an inverse correlation between CTPC% and BMMSC% (r = -0.056, P = 0.6). Conversely, a trend toward a positive correlation was noted between CTPC% and CXCR4⁺BMTPC% (r = 0.064, P = 0.6). Also, CXCR4⁺BMTPC% was higher in the patient group with a BMMSC% ≥ 0.024% when compared to the group with BMMSC% < 0.024% (P = 0.03). CTPC% showed a significant positive correlation with BMPC% on light microscopy (P = 0.001). In addition, the median BMMSC% was lower in patients with TP53 deletion (P = 0.03).

Conclusions: The load of CTPC in patients of NDMM showed a trend towards inverse correlation with quantity of BMMSC and conversely a positive correlation with quantity of CXCR4-expressing-BMTPC. Interestingly, BMMSC% was lower in patients with TP53 deletion. The quantity of BMMSC may influence the load of CTPC and may also be associated with other prognostic markers in patients of NDMM. Data from larger cohorts may yield corroborative evidence and have implications in understanding disease biology as well as proposing alternate therapeutic intervention strategies.