Clinical Utilization of Chimeric Antigen Receptor T Cells in B Cell Acute Lymphoblastic Leukemia: An Expert Opinion from the European Society for Blood and Marrow Transplantation and the American Society for Blood and Marrow Transplantation

Ankit J Kansagra; Noelle V Frey; Merav Bar; Theodore W Laetsch; Paul A Carpenter; Bipin N Savani; Helen E Heslop; Catherine M Bollard; Krishna V Komanduri; Dennis A Gastineau; Christian Chabannon; Miguel A Perales; Michael Hudecek; Mahmoud Aljurf; Leslie Andritsos; John A Barrett; Veronika Bachanova; Chiara Bonini; Armin Ghobadi; Saar I Gill; Joshua Hill; Saad Kenderian; Partow Kebriaei; Arnon Nagler; David Maloney; Hien D Liu; Nirali N Shah; Mohamed A Kharfan-Dabaja; Elizabeth J Shpall; Ghulam J Mufti; Laura Johnston; Elad Jacoby; Ali Bazarbachi; John F DiPersio; Steven Z Pavletic; David L Porter; Stephan A Grupp; Michel Sadelain; Mark R Litzow; Mohamad Mohty; Shahrukh K Hashmi

doi:10.1016/j.bbmt.2018.12.068

Clinical Utilization of Chimeric Antigen Receptor T Cells in B Cell Acute Lymphoblastic Leukemia: An Expert Opinion from the European Society for Blood and Marrow Transplantation and the American Society for Blood and Marrow Transplantation

Biol Blood Marrow Transplant. 2019 Mar;25(3):e76-e85. doi: 10.1016/j.bbmt.2018.12.068. Epub 2018 Dec 18.

Authors

Ankit J Kansagra¹, Noelle V Frey², Merav Bar³, Theodore W Laetsch⁴, Paul A Carpenter³, Bipin N Savani⁵, Helen E Heslop⁶, Catherine M Bollard⁷, Krishna V Komanduri⁸, Dennis A Gastineau⁹, Christian Chabannon¹⁰, Miguel A Perales¹¹, Michael Hudecek¹², Mahmoud Aljurf¹³, Leslie Andritsos¹⁴, John A Barrett¹⁵, Veronika Bachanova¹⁶, Chiara Bonini¹⁷, Armin Ghobadi¹⁸, Saar I Gill², Joshua Hill³, Saad Kenderian¹⁹, Partow Kebriaei²⁰, Arnon Nagler²¹, David Maloney³, Hien D Liu²², Nirali N Shah²³, Mohamed A Kharfan-Dabaja²⁴, Elizabeth J Shpall²⁰, Ghulam J Mufti²⁵, Laura Johnston²⁶, Elad Jacoby²¹, Ali Bazarbachi²⁷, John F DiPersio¹⁸, Steven Z Pavletic²⁸, David L Porter², Stephan A Grupp²⁹, Michel Sadelain³⁰, Mark R Litzow³¹, Mohamad Mohty³², Shahrukh K Hashmi³³

Affiliations

¹ Department of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
² Cell Therapy and Transplant Program, Abramson Cancer Center and the Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, Pennsylvania.
³ Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington.
⁴ Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Texas Southwestern Medical Center and Children's Health, Dallas, Texas.
⁵ Division of Hematology/Oncology, Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
⁶ Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, Texas.
⁷ Center for Cancer and Immunology Research, Children's National Health System, Washington, DC.
⁸ Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, Florida.
⁹ Department of Laboratory Medicine and Pathology, Mayo Clinic, Phoenix, Arizona.
¹⁰ Institut Paoli-Calmettes, Centre de Lutte Contre le Cancer; Centre d'Investigations Cliniques en Biothérapie, Université d'Aix-Marseille, Inserm CBT 1409, Marseille, France.
¹¹ Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
¹² Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.
¹³ Oncology Centre, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
¹⁴ Division of Hematology, Ohio State University Wexner Medical Center, Columbus, Ohio.
¹⁵ Stem Cell Transplantation and Cellular Therapy Program, GW Cancer Center, George Washington University, Washington, DC.
¹⁶ Division of Hematology/Oncology/Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
¹⁷ Experimental Hematology Unit, University Vita-Salute San Raffaele and Ospedale San Raffaele, Milano, Italy.
¹⁸ Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
¹⁹ Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota; Department of Immunology, Mayo Clinic, Rochester, Minnesota.
²⁰ Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
²¹ The Chaim Sheba Medical Center, Tel-Hashomer, Affiliated with the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
²² H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
²³ Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
²⁴ Division of Hematology-Oncology, Mayo Clinic, Jacksonville, Florida.
²⁵ Department of Haematological Medicine, King's College, London, United Kingdom.
²⁶ Department of Medicine, Stanford University School of Medicine, Stanford, California.
²⁷ Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
²⁸ Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
²⁹ Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania.
³⁰ Center for Cell Engineering and Immunology Program, Sloan Kettering Institute, New York, New York.
³¹ Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
³² Hôpital Saint-Antoine, APHP, Sorbonne Universite, INSERM UMRs 938, Paris, France.
³³ Oncology Centre, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia; Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota. Electronic address: [email protected].

Abstract

On August 30, 2017 the US Food and Drug Administration approved tisagenlecleucel (Kymriah; Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present, ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring, and disease assessments. To address these issues experts representing the American Society for Blood and Marrow Transplant, the European Society for Blood and Marrow Transplantation, the International Society of Cell and Gene Therapy, and the Foundation for the Accreditation of Cellular Therapy formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved.

Keywords: Chimeric antigen receptor; Leukemia; T cell.

MeSH terms

Antigens, CD19 / immunology
Child
Critical Pathways
Drug Approval
Expert Testimony*
Humans
Immunotherapy, Adoptive / methods*
Practice Patterns, Physicians'
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / therapy*
Receptors, Antigen, T-Cell / therapeutic use*
Societies, Medical
Vereinigte Staaten
Young Adult

Substances

Antigens, CD19
Receptors, Antigen, T-Cell
tisagenlecleucel

Grants and funding

Z99 CA999999/ImNIH/Intramural NIH HHS/United States