Axicabtagene ciloleucel (YESCARTA; Kite Pharma, a Gilead Company, Los Angeles CA) and tisagenlecleucel (KYMRIAH; Novartis Pharmaceuticals Corp., Basel, Switzerland) are two CD19-directed chimeric antigen receptor (CAR) T cell products currently approved by the US Food and Drug Administration; the European Medicines Agency; Health Canada; Ministry of Health, Labor and Welfare (Japan); and Therapeutic Goods Administration (Australia) for treatment of specific subtypes of relapsed/refractory aggressive B cell non-Hodgkin lymphoma (NHL). Although this approval has been transformative in the use of cellular immunotherapy in lymphoma, there are concerns regarding appropriate use of this novel therapy and of short- and long-term toxicities. To address these issues, representatives of the American Society of Transplantation and Cellular Therapy convened to recognize and address key issues surrounding the clinical application of CD19 CAR T cell therapy in B cell lymphomas, in collaboration with worldwide experts. The aim of this article is to provide consensus opinion from experts in the fields of hematopoietic cell transplantation, cellular immunotherapy, and lymphoma regarding key clinical questions pertinent to the use of CD19 CAR T cell products for the treatment of NHL. As the clinical practice using CAR T cells grows worldwide, we anticipate that this guidance will be relevant for hematology/oncology physicians who care for patients with lymphomas.
Bibliographical noteFunding Information:
Financial disclosure: The authors have nothing to disclose. Conflict of interest statement: A.J.K.: Advisory board?Jansen, Celgene. E.A.C.: Consulting?Novartis, Tessa. S.K.H.: Educational honorarium?Pfizer, Janssen, Novartis, Mallinckrodt. S.S.N.: Research support?Kite/Gilead, Merck, BMS, Cellectis, Poseida, Karus, Acerta, and Unum Therapeutics; Advisory board member/consultant?Kite/Gilead, Merck, Celgene, Novartis, Unum Therapeutics, Pfizer, Precision Biosciences, Cell Medica, Allogene, and Incyte. E.J.: Advisory board?Novartis. A.L.: Scientific advisory board?EUSA Pharma. C.A.J.: Consultancy?Kite, Novartis, Celgene, Humanigen, Pfizer, and Precision Biosciences; research funding?Pfizer. F.T.A.: Consultant?Pharmacyclics, Abbvie, AstraZeneca, Genentech, Sunesis, Blueprint Bio, Janssen, Gilead, Celgene; speakers bureau?Astrazeneca and Abbvie. V.B.: Funding?Novartis, UNUM therapeutics, Gamida Cell, Incyte, Cellgene; advisory board?Kite, Seattle Genetics. C.M.B.: Consulting or advisory role?Cellectis, Mana Therapeutics; stock options or other ownership?Mana Therapeutics, Torque, Neximmune, Cabaletta Bio. J.F.D.: Consulting/advisory committees?Cellworks, Tioma, Rivervest, Bioline, Amphivena and Bluebird, Celgene, Incyte, NeoImuneTech, Macrogenics; employment/salary?Washington University; ownership investment?Magenta, WUGEN. M.H.: Research support/funding?Takeda Pharmaceutical Company, Otsuka Pharmaceutical, Spectrum Pharmaceuticals, Astellas Pharma; Consultancy?Janssen, Incyte Corporation, ADC Therapeutics, Celgene Corporation, Pharmacyclics; speaker's bureau?Sanofi Genzyme. H.E.H.: Ownership equity?Allovir, Marker Therapeutics; advisory board?Gilead Biosciences, Cytosen, Tessa Therapeutics, Marker Therapeutics; research support?Cell Medica, Marker Therapeutics. J.A.H.: Consultant -Nohla Therapeutics and Amplyx; research support?Nohla Therapeutics, Shire, and Karius; DSMB member?HIV Vaccines Trials Network. K.V.K.: Ad hoc consultant?Kite/Gilead, Novartis, Celgene, Atara, Autolus, Kiadis, Helocyte. MM: lecture honoraria?Novartis. D.M.: Consultancy?Kite/Gilead, Juno/Celgene, Novartis, Miltenyi; research?Kite/Gilead, Miltenyi. SJS: Grants (to the University of Pennsylvania) and personal fees?Novartis, Celgene, Genentech, Merck, Pharmacyclics, Novartis, and Gilead; personal fees?Nordic Nanovector, Acerta, and Pfizer; patent?combination therapies of CAR and PD-1 inhibitors with royalties paid to Novartis. Other nonrelated conflicts of interests?Consultancy for Pharmacyclics and Daiichi Sankyo. M.A.P.: Honoraria?Abbvie, Bellicum, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda. D.S.M.B.?Servier and Medigene; scientific advisory boards?MolMed and NexImmune; research support?Incyte, Kite/Gilead, Miltenyi Biotec. Serves in a volunteer capacity as a member of the Board of Directors of the ASTCT and Be The Match (National Marrow Donor Program) and on the Center for International Blood and Marrow Transplant Research Cellular Immunotherapy Data Resource Committee. Y.L.: No personal compensation, funds to Mayo. Funding as PI for clinical trials?Kite/Gilead, Bluebird Bio, Celgene, Merck, Takeda, Janssen; funding for research ? Janssen; Advisory board?Kite/Gilead, Janssen, Celgene, Bluebird Bio, Novartis, JUNO; DSMB board?Sorrento. Authorship statement: T.J. M.B. A.J.K. and E.A.C. contributed equally to this work and wrote the first draft and subsequent revisions of the manuscript. M.A.K.D. M.A.P. and Y.L. contributed equally to this work. All authors contributed substantially to writing, critical review, and approval of the final draft of the manuscript. Financial disclosure: See Acknowledgments on page 14.
- Chimeric antigen receptor T cell therapy
- Diffuse large B cell lymphoma
- Non-Hodgkin lymphoma