Effect of Bortezomib Regimens and Daratumumab Monotherapy on Cellular Immunity in Multiple Myeloma Patients

Background: Treatment with a proteasome inhibitor (bortezomib) and daratumumab monoclonal anti CD38 antibody are effective in patients with multiple myeloma. However, these drugs impair cellular immunity, which may make the patients more prone to infection. Objective: To investigate the effect of bortezomib-based regimens and daratumumab monotherapy on the lymphocyte subpopulation in MM patients. Methods: Peripheral blood samples were collected from 32 patients, 29 were newly diagnosed and treated with bortezomib regimens and 3 patients were relapsed and refractory MM treated with daratumumab as monotherapy. The immunophenotypic analysis was performed by flow cytometry at baseline and during the third cycle of bortezomib regimen and fourth week of daratumumab treatment. Results: In the third cycle of bortezomib, there was a significant decrease in CD3(+) T cells, CD(+)4 T cells, memory T cells ,and natural killer cells (NK cells). However, CD8(+) T cells increased dramatically, followed by a significant reduction in the CD4/CD8 ratio. On the other hand, daratumumab led to an increase in the T cell population after four weeks of treatment, with a significant increase in CD3(+) T cells as well as CD4(+) T cells, while NK cells were dramatically depleted in all patients. Conclusion: Bortezomib hurt subsets of the T cells, while daratumumab positively affected the T cells subsets. In both treatments, NK cells decreased significantly. These results suggested that DARA is more specific to target myeloma cells than bortezomib. Also, DARA enhanced the T cells to extend especially CD3(+) T cells and CD4(+) T cells.