Caracterização de subpopulações linfocitárias e marcadores prognósticos em pacientes recém diagnosticados com mieloma múltiplo submetidos à terapia de primeira linha com ciclofosfamida, talidomida, dexametasona e daratumumabe.

Abstract

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 characterize lymphocyte subsets in patients with Multiple Myeloma eligible for Autologous Stem Cell Transplant (ASCT) using first-line therapy with cyclophosphamide, thalidomide, dexamethasone combined with daratumumab (CTd-Dara), an anti-CD38 monoclonal antibody. Between 2018 and 2022, 23 newly-diagnosed MM patients had their lymphocyte profiles analyzed at five distinct time points, and the therapeutic response was monitored by Next-Generation Flow (NGF), through the detection of measurable residual disease (MRD). It was observed that the treatment induced significant changes in the lymphocyte profile, with emphasis on the decrease in B cells and NK cells. The composition of the B cell subsets changed significantly throughout the treatment. When evaluating prognostic variables, the expression of the CD38 molecule on the surface of plasma cells emerged as a promising marker, correlating with lower MRD levels for this therapy and the R-ISS system. Although the lymphocyte subpopulations and Circulating Tumor Cells (CTCs) did not achieve statistical significance in prognostic terms, they indicate a pattern warranting further investigation. These findings enhance our understanding of the immunomodulatory effects of therapies in MM and signal ways to optimize treatments and patient monitoring.