CAR T-cell therapy in mature lymphoid malignancies: clinical opportunities and challenges

Abstract

The advent of chimeric antigen receptor T-cell (CAR T-cell) therapy has revolutionized the treatment paradigm of various hematologic malignancies. Ever since its first approval for treatment of acute lymphoblastic leukemia (ALL) in 2017, CAR T-cell therapy has been found to be efficacious in various other lymphoid malignancies, with recent approvals in diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). Although CAR T-cell therapeutics offer a novel immunotherapeutic approach to treat otherwise refractory malignancies, the plethora of studies/products and complexities in manufacturing and administration have led to several challenges for clinicians and the healthcare system as a whole. Some of the areas of unmet need include manufacturing delays, short persistence of CAR T-cells in circulation, lack of predictive biomarkers for efficacy and toxicity, and high cost of therapy. In this review, we evaluate the existing data on the efficacy and safety of CAR T-cell therapies in mature lymphoid malignancies [lymphomas, chronic lymphocytic leukemia (CLL), and multiple myeloma]. We also provide an in-depth review of the challenges posed by CAR T-cell therapeutics and potential strategies to overcome them. With newer CAR T-cell products and incorporation of measures to mitigate toxicities pertaining to cytokine release and neurological syndromes, there is a potential to overcome several of these challenges in the near future.Finally, as CAR T-cell therapy gains regulatory approval for more indications, there is a need to tackle the financial toxicity posed by this modality to sustain patient access.

The Diagnostic and Treatment Challenges of Concomitant Mantle Cell Lymphoma and IgM Myeloma

“…Our patient had an excellent response to the R-KCD regimen with lenalidomide. Various advancements in newer techniques, such as the introduction of chimeric antigen receptor T-cell (CAR T-cell) therapy, show promise for the treatment of refractory cancers including MM and MCL [13] . It will be fascinating to see where the future leads us.…”

Chemoresistance-Related Stem Cell Signaling in Osteosarcoma and Its Plausible Contribution to Poor Therapeutic Response: A Discussion That Still Matters

“…This molecule is described to play a crucial role in T cell function inhibition [ 243 ]. Despite the advantages of CAR T cell therapy and its increasing usage in clinical practice in lymphomas and acute lymphocytic leukemia [ 244 ], its applicability in solid tumors presents multiple challenges [ 245 ]. In terms of production, the viral transduction variation efficiency, as well as the high cost and time-consuming nature of the T cell-manufacturing procedure, is a problem.…”

Clinician and administrator perspectives on outpatient administration of ciltacabtagene autoleucel in relapsed or refractory multiple myeloma

“…Chimeric antigen receptor (CAR) T-cell therapy (CAR T therapy) has transformed treatment paradigms for patients with B-cell malignancies, including leukemia, lymphoma, and multiple myeloma ( 1 , 2 ). CAR T cell therapy involves genetically modifying a patient’s own T-cells ex-vivo to express a CAR, generating specificity of the patients’ T-cells to specific proteins on tumor cells, and has led to a remarkable improvement in treatment outcomes such as overall response and overall survival ( 1 , 3 , 4 ).…”