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Chimeric antigen receptor T cell therapy for non-Hodgkin lymphoma.

ABSTRACT: Non-Hodgkin Lymphoma (NHL) is the most common hematologic malignancy. More than 20,000 people in United States, more than 37,000 people in Europe and more than 199,000 people worldwide die of NHL every year. Recent advances in immunotherapeutic approaches for cancer have resulted in development of new classes of very effective immunotherapeutic approaches including chimeric antigen receptor T (CAR-T) cell therapy that are designed to bypass cancer immune evasion. Here, we review recent advances in CAR-T cell therapy for NHL. US food and drug administration (FDA) recently approved axicabtagene ciloleucel (Yescarta) a CD19 CAR T cell therapy for treatment of relapsed refractory diffuse large B cell lymphoma (DLBCL), high grade lymphoma, and primary mediastinal B cell lymphoma (PMBCL). Approval of Yescarta and rapid development of other CAR T cell therapies at various stages of development are opening up the door for a new wave of CAR T cell therapies that will dramatically change the way we treat NHL and hopefully other malignancies in the near future.

SUBMITTER: Ghobadi A

PROVIDER: S-EPMC5990429 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Chimeric antigen receptor T cell therapy for non-Hodgkin lymphoma.

Ghobadi Armin A

Current research in translational medicine 20180411 2

Non-Hodgkin Lymphoma (NHL) is the most common hematologic malignancy. More than 20,000 people in United States, more than 37,000 people in Europe and more than 199,000 people worldwide die of NHL every year. Recent advances in immunotherapeutic approaches for cancer have resulted in development of new classes of very effective immunotherapeutic approaches including chimeric antigen receptor T (CAR-T) cell therapy that are designed to bypass cancer immune evasion. Here, we review recent advances ...[more]

PMID: 29655961

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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.

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.

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Chimeric antigen receptor T cell therapy for non-Hodgkin lymphoma.

Publications

Chimeric antigen receptor T cell therapy for non-Hodgkin lymphoma.

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