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A Review of Chimeric Antigen Receptor T-Cell Therapy for Myeloma and Lymphoma.

ABSTRACT: Collectively, hematological malignancies account for the fourth most common malignancy. Myeloma and lymphoma are the most common types of hematological malignancies. Unfortunately, the management of refractory myeloma and lymphoma remains challenging. The discovery of new immunological therapies, namely chimeric antigen receptors T cells (CAR-T), outlined unprecedented B cell malignancies results. In this context, the CAR-T-based approach has led to the proliferation of many clinical studies. In this review, we will deal with the CAR-T structure, and we will summarize the primary clinical studies assessing the risks and benefits of CAR-T cell therapy. We will also deal with the adverse events and management of cytokine release syndromes/immune effector cell-associated neurotoxicity syndrome (ICANS). Subsequently, we will review potential future improvements to overcome refractoriness and improve expansion while decreasing CAR-T's off-target effects. The advances in the CAR-T platform represent a step forward with promising unlimited future possibilities that made it a paradigm-shifting for the management of B cell malignancies.

SUBMITTER: Atrash S

PROVIDER: S-EPMC8009535 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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A Review of Chimeric Antigen Receptor T-Cell Therapy for Myeloma and Lymphoma.

Atrash Shebli S Moyo Tamara K TK

OncoTargets and therapy 20210326

Collectively, hematological malignancies account for the fourth most common malignancy. Myeloma and lymphoma are the most common types of hematological malignancies. Unfortunately, the management of refractory myeloma and lymphoma remains challenging. The discovery of new immunological therapies, namely chimeric antigen receptors T cells (CAR-T), outlined unprecedented B cell malignancies results. In this context, the CAR-T-based approach has led to the proliferation of many clinical studies. In ...[more]

PMID: 33814917

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Project description:Multiple myeloma (MM) remains an incurable disease regardless of recent advances in the field. Therefore, a substantial unmet need exists to treat patients with relapsed/refractory myeloma. The use of novel agents such as daratumumab, elotuzumab, carfilzomib, or pomalidomide, among others, usually cannot completely eradicate myeloma cells. Although these new drugs have had a significant impact on the prognosis of MM patients, the vast majority ultimately become refractory or can no longer be treated due to toxicity of prior treatment, and thus succumb to the disease. Cellular therapies represent a novel approach with a unique mechanism of action against myeloma with the potential to defeat drug resistance and achieve long-term remissions. Genetic modification of cells to express a novel receptor with tumor antigen specificity is currently being explored in myeloma. Chimeric antigen receptor gene-modified T-cells (CAR T-cells) have shown to be the most promising approach so far. CAR T-cells have shown to induce durable complete remissions in other advanced hematologic malignancies like acute lymphocytic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). With this background, significant efforts are underway to develop CAR-based therapies for MM. Currently, several antigen targets, including CD138, CD19, immunoglobulin kappa (Ig-Kappa) and B-cell maturation antigen (BCMA), are being used in clinical trials to treat myeloma patients. Some of these trials have shown promising results, especially in terms of response rates. However, the absence of a plateau is observed in most studies which correlates with the absence of durable remissions. Therefore, several potential limitations such as lack of effectiveness, off-tumor toxicities, and antigen loss or interference with soluble proteins could hamper the efficacy of CAR T-cells in myeloma. In this review, we will focus on clinical outcomes reported with CAR T-cells in myeloma, as well as on CAR T-cell limitations and how to overcome them with next generation of CAR T-cells.

Dataset Information

A Review of Chimeric Antigen Receptor T-Cell Therapy for Myeloma and Lymphoma.

Publications

A Review of Chimeric Antigen Receptor T-Cell Therapy for Myeloma and Lymphoma.

Similar Datasets

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