Abstract
Immunomodulatory drugs (IMiDs) are effective treatments for patients with multiple myeloma. IMiDs have pleotropic effects including targeting the myeloma cells directly, and improving the anti-myeloma immune response. In the absence of myeloma cells, lenalidomide and pomalidomide induce CD4+ T cell secretion of IL-2 and indirect activation of Natural Killer (NK) cells. In the context of T cell receptor ligation, IMiDs enhance T cell proliferation, cytokine release and Th1 responses, both in vivo and in vitro. Furthermore, combination treatment of IMiDs and myeloma-targeting monoclonal antibodies eg. daratumumab (anti-CD38) and elotuzumab (anti-SLAMF7), checkpoint inhibitors, or bispecific T cell engagers showed synergistic effects, mainly via enhanced T and NK cell dependent cellular toxicity and T cell proliferation. Conversely, the corticosteroid dexamethasone can impair the immune modulatory effects of IMiDs, indicating that careful choice of myeloma drugs in combination with IMiDs is key for the best anti-myeloma therapeutic efficacy. This review presents an overview of the role for T cells in the overall anti-myeloma effects of immunomodulatory drugs.
Highlights
Multiple myeloma (MM) is a plasma B cell malignancy primarily localized to the bone marrow and characterized by immune dysfunction due to the complex interplay between the malignant plasma cells (PC) and immune cells in the tumor microenvironment [1]
Due to its problematic side effects and improved efficacy of the subsequent IMiDs, thalidomide has progressively been replaced by lenalidomide and pomalidomide in the myeloma treatment paradigm; currently IMiDs are used in newly diagnosed MM (NDMM) patients, in maintenance therapy post autologous stem cell transplantation and in patients with relapsed refractory multiple myeloma (RRMM) [4]
Several studies have shown that myeloma cell survival and immune escape is facilitated by impaired endogenous signaling in immune cells [2, 14]
Summary
Multiple myeloma (MM) is a plasma B cell malignancy primarily localized to the bone marrow and characterized by immune dysfunction due to the complex interplay between the malignant plasma cells (PC) and immune cells in the tumor microenvironment [1]. New therapeutic approaches in the last two decades have dramatically improved patient outcomes. These include the incorporation of immunomodulatory drugs (IMiDs) that exert pleiotropic effects including directly acting on the malignant cells and enhancing T and NK cell anti-myeloma properties [2]
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