About this Research Topic
Clonal plasma cell (PC) disorders are a spectrum of monoclonal gammopathies characterised by the accumulation of PCs, primarily in the bone marrow (BM) with the capacity to over-produce a monoclonal protein. At one end of this spectrum is the pre-malignant disorder, monoclonal gammopathy of undetermined significance (MGUS), and at the other end are symptomatic malignancies such as multiple myeloma (MM) and Waldenström macroglobulinemia (WM). While the majority of MM patients progress to refractory fatal disease, some survive long term up to 20 years after disease onset. It is unknown why some patients progress from MGUS to MM, or why some treated MM patients relapse early while others stay in remission for many years. The immune system may be the key to disease control, in particular the capacity of T cells to kill malignant PCs, and its regulation by cellular and non-cellular components in the BM microenvironment. When compared to MGUS and MM, T cells in WM are even less understood.
Researchers continue to improve the understanding of the changes in both conventional and unconventional T cells during myeloma evolution from MGUS and those induced by treatment. These alterations are potential targets for checkpoint blockade immunotherapy aiming to reinvigorate T cell functionality. However, checkpoint blockade using PD1/PDL1 inhibitors alone or combined with standard therapy demonstrated limited benefit in MM with trials terminated due to unexpected deaths in checkpoint arm. Some of these deaths may be caused by immune-related adverse events and severe toxicity associated with combination regimens. Understanding how combination regimens involving checkpoint blockade and associated adverse events affect T cell biology is essential to improving patient outcome. CAR T-cell therapy targeting BCMA and other plasma cell antigens, and bispecific T-cell engager AMG 420 that targets BCMA on myeloma and CD3 on T cells show promising results in clinical trials. This raises the possibility that AMG 420 could be used as an off-the-shelf alternative for complicated and expensive CAR T-cell therapy. How these therapies preserve T cell functionality remains to be addressed. There are data-sets on the horizon from a previous Research Topic covering 3D organoid myeloma modelling, which allows for personalized treatment, testing and analysing of T cell and PC interactions within the BM microenvironment. That topic deals with autologous stem cell transplantation (ASCT), which remains the standard treatments for MM patients. This Research Topic seeks to harness T cells within ASCT to induce curative autologous graft-vs-myeloma effects and has the potential to change clinical practice for MM.
In this Research Topic, we welcome Original Research, Review, Mini Review and Opinion articles, addressing T cells in PC disorders using animal models, personalized 3D modelling platform and human samples. Basic research topics on T cells in WM, and Opinions on immunotherapy for MM and WM with focus on T cells are encouraged.
More specifically, topics of interest include, but are not limited to:
• T cells during disease evolution from premalignant MGUS and smouldering myeloma to malignant MM, and WM.
• T cells and associated immune-related adverse events during myeloma combination regimens involving checkpoint blockade immunotherapy.
• How CAR T-cell, bispecific T-cell engagers and other adoptive cellular therapies enhance T cells functionality in MM patients.
• How the bone marrow microenvironment influences T cells during myeloma development and treatment.
• Studies on T cells using personalized 3D organoid myeloma modelling platforms.
• Harnessing T cells within ASCT to induce curative autologous graft-vs-myeloma effects.
• Understanding the role of T-cells in the antimyeloma effect of immunomodulatory drugs
Dr. Kumar has received funding for clinical trials from: Celgene, Takeda, Janssen, BMS, KITE, Merck, Abbvie, Medimmune, Novartis, Roche-Genentech, Amgen, Tenebio, Carsgen. The other Topic Editors declare no conflict of interest with relation to the theme.'
Keywords: plasma cell disorders, T Cells, MGUS, Multiple myeloma, cancer immunotherapy
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