Review Articles
Vol. 15 No. 1 (2023): Review Articles, Original Article, Scientific Letter, Case Reports Letter to the Editor
CAR-T CELL THERAPY IN LARGE B CELL LYMPHOMA
CAR-T; Large B Cell Lymphoma; Salvage Therapy,
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Received: October 9, 2023
Accepted: October 10, 2023
Accepted: October 10, 2023
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Large B-cell lymphomas (LBCLs) are among the most frequent (about 30%) non-Hodgkin’s lymphoma. Despite the aggressive behavior of these lymphomas, more than 60% of patients can be cured with first-line chemoimmunotherapy using the R-CHOP regimen. Patients with refractory or relapsing disease show a poor outcome even when treated with second-line therapies.
CD19-targeted chimeric antigen receptor (CAR) T-cells are emerging as an efficacious second-line treatment strategy for patients with LBCL. Three CD19-CAR-T-cell products received FDA and EMA approval. The use of CAR-T cell therapy has also been explored for the treatment of high-risk LBCL patients in the first-line setting and for patients with central nervous system involvement.
Although CD19-CAR-T therapy has transformed the care of refractory/relapsed LBCL, about 60% of these patients will ultimately progress or relapse following CD19-CAR-T: therefore, it is fundamental to identify predictive criteria of response to CAR-T therapy and to develop salvage therapies for patients relapsing after CD19-CAR-T therapies. Moreover, ongoing clinical trials are evaluating bispecific CAR-T cells targeting both CD19 and CD20 or CD19 and CD22 as a tool to improve the therapeutic efficacy and to reduce the number of refractory/relapsing patients.
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Fig.1 Schematic representation of CD19-CAR constructs currently available commercially and used for the therapy of DLBCL patients. All these products have a second-generation CAR construct, consisting of an antigen-binding domain, a hinge region, a transmembrane region, a co-stimulatory domain and a T-cell activation domain.
Fig. 2: Patients DCBL Disease-free Survival and Overall Survival of the three randomized trials of 19-CAR T-cell vs. Standard Care: BELINDA, Engl J Med 2022, 386(7): 629-639; ZUMA-7, N Engl J Med 2023, 2023 Jul 13;389(2):148-157; TRANSFORM, Blood 2023; 141(14): 1675-1684. No differences in the Belinda trial; significant differences in the two other trials, mostly evident for Disease free survival.
How to Cite
“CAR-T CELL THERAPY IN LARGE B CELL LYMPHOMA: CAR-T; Large B Cell Lymphoma; Salvage Therapy”, (2023) Mediterranean Journal of Hematology and Infectious Diseases, 15(1), p. e2023066. doi:10.4084/MJHID.2023.066.
Copyright (c) 2023 Ugo Testa, Dr. Germana Castelli, Giuseppe Leone, Elvira Pelosi, Dr. Germana Castelli, Prof. Hohaus
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