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Additional possibilities of chimeric antigen receptor T-cells in B-cell lymphoma: combination therapy

ABSTRACT: B-cell non-Hodgkin’s lymphoma (B-NHL) is a lymphoproliferative disorder that affects B lymphocytes. Chimeric antigen receptor (CAR) T-cell immunotherapy is a new type of immunotherapy that uses genetic engineering techniques to modify and expand the patient’s autoimmune cells in vitro, after which these cells are reinfused into the patient. CAR-T cell immunotherapy has the potential to treat different types of B-cell lymphoma. Many clinical studies have shown that CAR-T cell therapy has significant antitumor effects on B-cell lymphoma. Although much work has been carried out to improve the efficacy of CAR-T cell therapy and to reduce associated side effects, there are still many issues to address. CAR-T cell therapy shows significant promise in treating B-NHL, but some patients still have a poor initial response to this therapy where the infused CAR-T cells show insufficient persistence. With the rapid development of immunological therapy, combination therapy has been certified to improve the efficacy of CAR-T cell therapy. Targeted drugs such as programmed death-1 (PD-1) inhibitors, programmed cell death-ligand 1 (PD-L1) inhibitors, and Bruton’s tyrosine kinase (BTK) inhibitors may further enhance the efficacy and reduce the side effects of CAR-T cell treatment. This article reviews the rationale and relevant clinical research on combination therapy based on CAR-T cell therapy for B-cell lymphoma treatment.

SUBMITTER: Yang Y

PROVIDER: S-EPMC8798430 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionGeographic access to novel oncology therapies, and the extent to which it may vary by potential sites of care, regions, and population characteristics, is poorly understood. We examined how expanding access to chimeric antigen receptor (CAR) T cell therapy administration sites impacts patient travel distances and time.MethodsWe used geographic information system techniques to calculate shortest travel distance and time between patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) and the nearest CAR T cell therapy administration site in three scenarios: academic hospitals; academic and community multispecialty hospitals; and academic and community multispecialty hospitals plus nonacademic specialty oncology network centers. Main outcome measures were differences in travel distance and time among the scenarios and the relationship between travel time and socioeconomic status, race, rural-urban areas, and non-Hodgkin lymphoma clusters. Non-Hodgkin lymphoma incidence, socioeconomic status, and administration centers were derived from governmental/publicly available data sources.ResultsOf 3922 patients eligible for CAR T cell therapy, more than 37% had to travel more than 1 h to the nearest academic hospital. Average travel time and distance were significantly reduced by 23% and 30% (P < 0.001), respectively, when access was expanded to include community hospitals plus a broader range of oncology specialty treatment centers. Compared to academic hospitals alone, increasing access to include community hospitals decreased time and distance by 7% and 8% (P < 0.01), respectively. In addition, there would be a lower proportion of sites operating as the only care provider within 25 miles if access was expanded outside of academic hospitals only. Longer travel time was associated with lower socioeconomic status.ConclusionMany patients with DLBCL have long travel times to an academic hospital that administers CAR T cell therapy. Expanding access to care through site-of-care planning will help address regional, rural-urban, and sociodemographic equity in the geographic allocation of CAR T cell therapy.

Project description:B-cell non-Hodgkin lymphoma (B-NHL) is a group of heterogeneous disease which remains incurable despite developments of standard chemotherapy regimens and new therapeutic agents in decades. Some individuals could have promising response to standard therapy while others are unresponsive to standard chemotherapy or relapse after autologous hematopoietic stem-cell transplantation (ASCT), which indicates the necessity to develop novel therapies for refractory or relapsed B-NHLs. In recent years, a novel cell therapy, chimeric antigen receptor T-cell therapy (CAR-T), was invented to overcome the limitation of traditional treatments. Patients with aggressive B-NHL are considered for CAR-T cell therapy when they have progressive lymphoma after second-line chemotherapy, relapse after ASCT, or require a third-line therapy. Clinical trials of anti-CD19 CAR-T cell therapy have manifested encouraging efficacy in refractory or relapsed B-NHL. However, adverse effects of this cellular therapy including cytokine release syndrome, neurotoxicity, tumor lysis syndrome and on-target, off-tumor toxicities should attract our enough attention despite the great anti-tumor effects of CAR-T cell therapy. Although CAR-T cell therapy has shown remarkable results in patients with B-NHL, the outcomes of patients with B-NHL were inferior to patients with acute lymphoblastic leukemia. The inferior response rate may be associated with physical barrier of lymphoma, tumor microenvironment and low quality of CAR-T cells manufactured from B-NHL patients. Besides, some patients relapsed after anti-CD19 CAR-T cell therapy, which possibly were due to limited CAR-T cells persistence, CD19 antigen escape or antigen down-regulation. Quite a few new antigen-targeted CAR-T products and new-generation CAR-T, for example, CD20-targeted CAR-T, CD79b-targeted CAR-T, CD37-targeted CAR-T, multi-antigen-targeted CAR-T, armored CAR-T and four-generation CAR-T are developing rapidly to figure out these deficiencies.

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Additional possibilities of chimeric antigen receptor T-cells in B-cell lymphoma: combination therapy

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