@article{b2524f1a9fc94a399fb553083c40b063,
title = "Changes in immune cell populations following KappaMab, lenalidomide and low-dose dexamethasone treatment in multiple myeloma",
abstract = "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 = "cytometry, dendritic cell, KappaMab, lenalidomide, myeloma, T cell",
author = "Norton, {Samuel E.} and Tiffany Khong and Malarmathy Ramachandran and Highton, {Andrew J.} and Ward-Hartstonge, {Kirsten A.} and Jake Shortt and Andrew Spencer and Kemp, {Roslyn A.}",
note = "Funding Information: We thank all patients and their families for participating in this study. This work was supported by HaemaLogiX Pty Ltd (formerly Immune System Therapeutics). Medarex (acquired by Bristol‐Myers Squibb) was the manufacturer of KappaMab. Immune System Therapeutics received a Commercial Ready Grant from the Australian Government to assist with funding for this study. The clinical trial and associated correlative studies were funded by a Victorian Cancer Agency Translational Research Project Grant (TRP15024). Open access publishing facilitated by Monash University, as part of the Wiley ‐ Monash University agreement via the Council of Australian University Librarians. Funding Information: We thank all patients and their families for participating in this study. This work was supported by HaemaLogiX Pty Ltd (formerly Immune System Therapeutics). Medarex (acquired by Bristol-Myers Squibb) was the manufacturer of KappaMab. Immune System Therapeutics received a Commercial Ready Grant from the Australian Government to assist with funding for this study. The clinical trial and associated correlative studies were funded by a Victorian Cancer Agency Translational Research Project Grant (TRP15024). Open access publishing facilitated by Monash University, as part of the Wiley - Monash University agreement via the Council of Australian University Librarians. Publisher Copyright: {\textcopyright} 2023 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.",
year = "2023",
doi = "10.1002/cti2.1478",
language = "English",
volume = "12",
journal = "Clinical & Translational Immunology",
issn = "2050-0068",
publisher = "John Wiley & Sons",
number = "12",
}