Beyond Chemotherapy: Checkpoint Inhibition and Cell-Based Therapy in Non-Hodgkin Lymphoma.
Am Soc Clin Oncol Educ Book
; 38: 592-603, 2018 May 23.
Article
en En
| MEDLINE
| ID: mdl-30231316
ABSTRACT
Immune-based treatment strategies, such as checkpoint inhibition and chimeric antigen receptor (CAR) T cells, have started a new frontier for treatment in non-Hodgkin lymphoma (NHL). Checkpoint inhibition has been most successful in Hodgkin lymphoma, where higher expression of PD-L1 is correlated with better overall response rate. Combinations of checkpoint inhibition with various chemotherapy or biologics are in clinical trials, with initially promising results and manageable safety profiles. CAR T-cell therapies that target CD19 are a promising and attractive therapy for B-cell NHLs, with a product approved by the US Food and Drug Administration in 2017. Changes in the target, hinge, or costimulatory domain can dramatically alter the persistence and efficacy of the CAR T cells. The ZUMA trials from Kite used CD19-(CD28z) CAR T cells, whereas the TRANSCEND studies from Juno and the JULIET studies from Novartis used CD19-(4-1BBz) CARs. Despite the recent successes with CAR T-cell clinical trials, major concerns associated with this therapy include cytokine release syndrome, potential neurotoxicities, B-cell aplasia, loss of tumor antigen leading to relapse, and cost and accessibility of the treatment. Although first-generation CAR T-cell therapies have failed in solid malignancies, newer second- and third-generation CAR T cells that target antigens other than CD19 (such as mesothelin or B-cell maturation antigen) are being studied in clinical trials for treatment of lung cancer or multiple myeloma. Overall, immune-based treatment strategies have given oncologists and patients hope when there used to be none, as well as a new basket of tools yet to come with further research and development.
Texto completo:
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfoma no Hodgkin
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Inmunoterapia Adoptiva
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Tratamiento Basado en Trasplante de Células y Tejidos
Límite:
Humans
Idioma:
En
Revista:
Am Soc Clin Oncol Educ Book
Año:
2018
Tipo del documento:
Article