Objectives: Lenalidomide (LEN) is used to treat multiple myeloma (MM) and shows in vitro synergy with KappaMab (KM), a chimeric antibody specific for Kappa Myeloma antigen, an antigen exclusively expressed on the surface of kappa-restricted MM cells. Lenalidomide, dexamethasone (DEX) and KM control MM via multiple immunomodulatory mechanisms; however, there are several additional effects of the drug combination on immune cells. Lenalidomide can increase T cell and NKT cell cytotoxicity and dendritic cell (DC) activation in vitro. We investigated the immune cell populations in bone marrow of patients treated with KM, LEN and low-dose DEX in kappa-restricted relapsed/refractory MM ex vivo and assessed association of those changes with patient outcome.
Methods: A cohort (n = 40) of patients with kappa-restricted relapsed/refractory MM, treated with KM, LEN and low-dose DEX, was analysed using a mass cytometry panel that allowed identification of immune cell subsets. Clustering analyses were used to determine significant changes in immune cell populations at time periods after treatment.
Results: We found changes in five DC and 17 T-cell populations throughout treatment. We showed an increase in activated conventional DC populations, a decrease in immature/precursor DC populations, a decrease in activated CD4 T cells and an increase in effector-memory CD4 T cells and effector CD8 T cells, indicating an activated immune response.
Conclusion: These data characterise the effects of LEN, DEX, and KM treatment on non-target immune cells in MM. Treatment may support destruction of MM cells by both direct action and indirect mechanisms via immune cells.
Keywords: KappaMab; T cell; cytometry; dendritic cell; lenalidomide; myeloma.
© 2023 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.