P-244: EFFECTS OF DARATUMUMAB(DARA), CYCLOPHOSPHAMIDE (C), THALIDOMIDE (T) AND DEXAMETHASONE (D) COMBINATION ON LYMPHOCYTE POPULATIONS OF TRANSPLANT ELIGIBLE NEWLY DIAGNOSE MULTIPLE MYELOMA PATIENTS

Introduction: Multiple Myeloma (MM) is the second most common hematological malignancy, resulting from the proliferation of monoclonal protein-producing plasma cells, predominantly affecting the elderly population. In the last decade, therapeutic advances have led to an increase in the overall survival of patients, however the disease remains incurable. Therapeutic protocols combining alkylating agents, immunomodulators, immunosuppressants, and immunotherapy induce an immunological shift that is still not fully understood.

The aim of this study was to quantify lymphocytes subpopulations and B cells subsets in patients with Newly diagnosed Multiple Myeloma (NDMM) eligible for Autologous Stem Cell Transplant (ASCT) using first-line therapy with cyclophosphamide, thalidomide, dexamethasone combined with daratumumab (Dara-CTd), an anti-CD38 monoclonal antibody.



Methods: Between 2018 and 2022, 23 NDMM patients from the MAXDARA clinical phase 2 trial had their lymphocyte profiles analyzed at five distinct time points: at diagnosis, after induction therapy, after two consolidation cycles post-ASCT, before maintenance therapy, and one year after the start of the maintenance phase. Flow cytometry was used to detect lymphocyte subsets by surface molecules including CD3, CD4, CD5, CD8, CD16, CD19, CD20, CD38, CD45 and CD56 in the scatter plot. B cells were isolated and subpopulations (naïve 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. Statistics was performed using the SPSS® v25.0



Results: The patients median age was 58 (range 37 – 67) years old, and 57% were female. It was observed that the treatment induced significant changes in the lymphocyte profile, with emphasis on the decrease in B cells and NK cells (p≤0,05). The composition of the B cell subsets changed significantly throughout the treatment. T cells had a significant decrease after the induction phase, but recovered soon post-ASCT. Although not statistically significant, higher lymphocyte counts were associated with higher overall free survival and measurable residual disease undetectable by next-generation flow (NGF).



Conclusions: Lymphopenia have been shown with different protocols using Dara as single agent or in combination. The present study confirmed that Dara-CTd induces 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 remains at low levels during treatment, with slow recovery.