• Paolo Strati, Shabnum Patel, Loretta Nastoupil, Michelle A Fanale, Catherine M Bollard, Adam Y Lin, and Leo I Gordon.
• From the Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX; Children's National Health System and The George Washington University, Washington, DC; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX; Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL.
• Am Soc Clin Oncol Educ Book. 2018 May 23; 38: 592-603.

AbstractImmune-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.

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