CD19-directed CAR T-cell therapy in B-cell NHL

Abstract

Purpose of review CD19-directed chimeric antigen receptor (CAR) T-cell therapy is a valuable new treatment option for patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma. The aim of this review is to give an overview of the pivotal phase I/II trials, emerging real-world evidence and ongoing trials. Recent findings For decades, attempts at improvement of the poor prognosis of patients with R/R large B-cell lymphoma with new treatment regimens have been disappointing. Since the first report of CD19-directed CAR-T-cell therapy in 2010, three constructs have been tested in large phase I/II trials and resulted in 30–40% durable responses. This has led to Food and Drug Administration and European Medicines Agency approval for axicabtagene ciloleucel and tisagenlecleucel and filing of the biologics license application for lisocabtagene maraleucel. Emerging real-world evidence seems to confirm the promising results. However, considerable toxicity, mainly cytokine release syndrome and neurotoxicity limits their general applicability and not all patients intended to be treated can be bridged during the manufacturing period due to kinetics of the disease. Randomized phase III clinical trials are being conducted to test anti-CD19 CAR-T-cell therapy in the second-line and several phase II trials are aiming to improve efficacy and decrease toxicity. Summary CD19-directed CAR-T-cell therapy has become standard of care for aggressive R/R diffuse large B-cell non-Hodgkin lymphoma (DLBCL), but challenges still remain.

CAR-T cells microscopic and phenotypic identification in the peripheral blood

“… 4 After being transduced, the CAR-T cells are reinjected by intravenous infusion. 5 The morphologic and immunophenotypic description of CAR-T cells observed in residual cells of CAR-T cells infusion bag has just been described by Galli et al in this journal. 6 Here we confirm their findings in the peripheral blood (PB) and report about our experience of CAR-T cells automated and microscopic detection and immune monitoring.…”

Cells to the Rescue: Emerging Cell-Based Treatment Approaches for NMOSD and MOGAD

“…B cell targeting using CAR-T cell therapy focuses on B cell markers CD19, CD20 and B cell maturation antigen (BCMA) as antigenic targets, for instance, in the field of B cell leukaemia [ 85 ], B cell lymphoma [ 86 , 87 ] and multiple myeloma [ 88 ]. Next to the oncological field, B cell overactivation has also been implicated in the field of autoimmunity, where dysregulated B cell activation leads to an antibody-mediated targeting of healthy own body tissue.…”

In-Vivo Induced CAR-T Cell for the Potential Breakthrough to Overcome the Barriers of Current CAR-T Cell Therapy

“…CAR-T cell therapy has demonstrated unprecedented response rates in patients with B cell lymphoma since the first approval of CD19-targeted CAR-T cells in the USA (1,(3)(4)(5). However, along with the remarkable achievements of CAR-T cell therapy, many systemic toxicities, such as cytokine release syndrome (CRS) and neurotoxicity, have also been frequently reported (2,(6)(7)(8). Additionally, the complex manufacturing process of CAR-T cells limits the broader applications of this therapeutic method as a standard clinical treatment (2,(9)(10)(11).…”