P-066: Effect of Daratumumab (DARA), Cyclophosphamide (C), T Halidomide (T) and Dexamethasone (D) combination of Lymphocyte populations of transplant eligible newly diagnosed Multiple Myeloma patients

Abstract

<h3>Background</h3> The CTD combination have both an immunomodulatory and immunosuppressive activity on multiple myeloma (MM) patients (pts) treatment. Dara, an antiCD38-antibody, effect on the immune system was already described, but few studies analyzed specifically lymphocytes population. We hypothesized that Dara-CTD combination could impact on lymphocytes subsets during treatment. The primary endpoint was to quantify subpopulations of lymphocytes in TE NDMM pts during Dara-CTD treatment phases. Secondary endpoint was to describe B cells subsets during the same phases. <h3>Methods</h3> Peripheral blood of 14 pts at four different time points was collected: at diagnose, after four cycles of Dara-CTD, after two consolidation cycles post ASCT and before maintenance therapy. Flow cytometry was used to detect lymphocyte surface molecules including CD3, CD4, CD5, CD8, CD16, CD19, CD20, CD38, CD45 and CD56 in the scatter plot. <h3>Results</h3> B cells were isolated and subpopulations (naive B cells, non-class switched memory B cells, class switched memory B cells, IgD-CD27- memory B cells and plasmablasts) were detected by CD20, CD24, CD27, CD38, CD45 and IgD. The median of T, B and NK lymphocytes subsets at diagnosis were 1153×10³/µL, 205×10³/µL and 284×10³/µL cells, respectively. After 4 cycles of Dara-CTD the median of T, B and NK cells dropped significantly to 889×10³/µL, 12×10³/µL and 11×10³/µL, respectively (p<0.05). The number of the cells after two consolidation cycles post-ASCT, showed T cells full recovery (1087×10³/µL) while B and NK cells had weakly reconstitution (15×10³/µL and 34×10³/µL, respectively). Before maintenance therapy, the median of T, B and NK cells were 1456×10³/µL, 24×10³/µL and 33 ×10³/µL, respectively. Regarding B cell population, the median of naive B cell decreased after 4 induction cycles from 32×10³/µL to 1×10³/µL. Then, after two consolidation cycles post-ASCT the number of B cell increased to 14×10³/µL and to 18×10³/µL before maintenance. The present study confirmed that there is a decrease in the number of different lymphocytes populations (T, B and NK) after induction therapy with Dara-CTD. The T cells number recovery after two consolidation cycles post-ASCT, but B and NK cells remain low after the same period. There was a slowly but continuously recovering of B and NK cells, suggesting that Dara-CTD combination allows lymphocytes reconstitution. Analyzing the B cells subpopulations, the naive B cell was the first to show a more significant recovery, although it was below the reference range (33–259). This is the first study that report the lymphocyte profile during Dara-CTD treatment. <h3>Conclusions</h3> This preliminary data suggest that Dara-CTD induces general lymphopenia on (T, B and NK) populations after induction phase. It was identified that T cells recovery was complete after two consolidations cycles while the recovery of B and NK cells was slowly but continuously.