Clinical utilization of Chimeric Antigen Receptor T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL)-an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplantation (ASBMT)

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 A Hill³, Saad Kenderian^{19

20}, Partow Kebriaei²¹, Arnon Nagler²², David Maloney³, Hien D Liu²³, Nirali N Shah²⁴, Mohamed A Kharfan-Dabaja²⁵, Elizabeth J Shpall²², Ghulam J Mufti²⁶, Laura Johnston²⁷, Elad Jacoby²³, Ali Bazarbachi²⁸, John F DiPersio¹⁹, Steven Z Pavletic²⁹, David L Porter², Stephan A Grupp³⁰, Michel Sadelain³¹, Mark R Litzow³², Mohamad Mohty³³, Shahrukh K Hashmi^{34

35}

Affiliations

¹ Department of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
² Cell Therapy and Transplant Program, Abramson Cancer Center and the Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA.
³ Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA.
⁴ Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Texas Southwestern Medical Center and Children's Health, Dallas, TX, USA.
⁵ Division of Hematology/Oncology, Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
⁶ Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, TX, USA.
⁷ Center for Cancer and Immunology Research, Children's National Health System, Washington, DC, USA.
⁸ Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL, USA.
⁹ Department of Laboratory Medicine and Pathology, Mayo Clinic, Phoenix, AZ, USA.
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 Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA.
¹² Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.
¹³ Oncology Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
¹⁴ Division of Hematology, Ohio State University Wexner Medical Center, Columbus, OH, USA.
¹⁵ Stem Cell Transplantation and Cellular Therapy Program, GW Cancer Center, George Washington University, Washington, DC, USA.
¹⁶ Division of Hematology/Oncology/Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
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, MO, USA.
¹⁹ Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
²⁰ Department of Immunology, Mayo Clinic, Rochester, MN, USA.
²¹ Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
²² The Chaim Sheba Medical Center, Tel-Hashomer, Affiliated with the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
²³ H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
²⁴ Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
²⁵ Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL, USA.
²⁶ Department of Haematological Medicine, King's College, London, UK.
²⁷ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
²⁸ Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
²⁹ Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
³⁰ Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA.
³¹ Center for Cell Engineering and Immunology Program, Sloan Kettering Institute, New York, NY, USA.
³² Department of Immunology, Mayo Clinic, Rochester, MN, USA. litzow.mark@mayo.edu.
³³ Hôpital Saint-Antoine, APHP, Sorbonne Universite, INSERM UMRs 938, Paris, France. Mohamed.mohty@inserm.fr.
³⁴ Division of Hematology, Ohio State University Wexner Medical Center, Columbus, OH, USA. hashmi.shahrukh@mayo.edu.
³⁵ Department of Immunology, Mayo Clinic, Rochester, MN, USA. hashmi.shahrukh@mayo.edu.

PMID: 31092900
PMCID: PMC8268756
DOI: 10.1038/s41409-019-0451-2

Clinical utilization of Chimeric Antigen Receptor T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL)-an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplantation (ASBMT)

Ankit J Kansagra et al. Bone Marrow Transplant. 2019 Nov.

. 2019 Nov;54(11):1868-1880.

doi: 10.1038/s41409-019-0451-2. Epub 2019 May 15.

Authors

Affiliations

¹ Department of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
² Cell Therapy and Transplant Program, Abramson Cancer Center and the Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA.
³ Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA.
⁴ Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Texas Southwestern Medical Center and Children's Health, Dallas, TX, USA.
⁵ Division of Hematology/Oncology, Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
⁶ Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital, Houston, TX, USA.
⁷ Center for Cancer and Immunology Research, Children's National Health System, Washington, DC, USA.
⁸ Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL, USA.
⁹ Department of Laboratory Medicine and Pathology, Mayo Clinic, Phoenix, AZ, USA.
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 Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA.
¹² Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.
¹³ Oncology Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
¹⁴ Division of Hematology, Ohio State University Wexner Medical Center, Columbus, OH, USA.
¹⁵ Stem Cell Transplantation and Cellular Therapy Program, GW Cancer Center, George Washington University, Washington, DC, USA.
¹⁶ Division of Hematology/Oncology/Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
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, MO, USA.
¹⁹ Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
²⁰ Department of Immunology, Mayo Clinic, Rochester, MN, USA.
²¹ Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
²² The Chaim Sheba Medical Center, Tel-Hashomer, Affiliated with the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
²³ H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
²⁴ Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
²⁵ Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL, USA.
²⁶ Department of Haematological Medicine, King's College, London, UK.
²⁷ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
²⁸ Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
²⁹ Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
³⁰ Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA.
³¹ Center for Cell Engineering and Immunology Program, Sloan Kettering Institute, New York, NY, USA.
³² Department of Immunology, Mayo Clinic, Rochester, MN, USA. litzow.mark@mayo.edu.
³³ Hôpital Saint-Antoine, APHP, Sorbonne Universite, INSERM UMRs 938, Paris, France. Mohamed.mohty@inserm.fr.
³⁴ Division of Hematology, Ohio State University Wexner Medical Center, Columbus, OH, USA. hashmi.shahrukh@mayo.edu.
³⁵ Department of Immunology, Mayo Clinic, Rochester, MN, USA. hashmi.shahrukh@mayo.edu.

PMID: 31092900
PMCID: PMC8268756
DOI: 10.1038/s41409-019-0451-2

Erratum in

Publisher Correction: Publisher correction for multiple articles.
[No authors listed] [No authors listed] Bone Marrow Transplant. 2023 Apr;58(4):469. doi: 10.1038/s41409-022-01891-4. Bone Marrow Transplant. 2023. PMID: 36596883 Free PMC article. No abstract available.

Abstract

On August 30, 2017, the U.S. Food and Drug Administration (US-FDA) 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 (ASBMT), the European Group for Blood and Marrow Transplantation (EBMT), the International Society of Cell and Gene Therapy (ISCT), and the Foundation for the Accreditation of Cellular Therapy (FACT), 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.

PubMed Disclaimer

Conflict of interest statement

AJK: Scientific Advisory Board–Celgene. NVF: Consultant–Novartis, Servier. TWL: Consultant–Novartis CMB: Scientific Advisory Boards: Cellectis. Stock/ownership: Mana Therapeutics, Torque and Neximmune. KK: Scientific Advisory Boards: Kite/Gilead, Novartis, Juno/Celgene, Atara, Takeda; Clinical Research Site: Kite, Iovance, Juno, Atara. CC: Consultant–Gilead, Research Funding: Gilead, Celgene, Speaker: Terumo BCT, Novartis. MAP: Honorarium: Abbvie, Bellicum, Incyte, Merck, Novartis, Nektar Therapeutics, and Takeda. Data Safety Monitoring Board: Servier and Medigene, Scientific Advisory Boards–MolMed and NexImmune. Research Funding–Incyte, Miltenyi Biotec. LA: Board of director/Scientific Advisory Board: HCLF, Consultant: AstraZeneca. VB: Research Funding–Gamida Cell, GT Biopharma, Scientific Advisory Board - Novartis, Kite, Travel funding–Amgen. CB: Research Funding–Intellia Therapeutics, Scientific Advisory Boards - TxCell, MolMed s.p.a., Travel funding–Miltenyi. SAG: Research Funding–Novartis, Servier and Kite. Consultant/Study Steering Committees/Scientific Advisory Boards–Novartis, Adaptimmune, Eureka, TCR2, Juno, GlaxoSmithKline, Cellectis, Vertex, and Roche. JAH: Consultant–Nohla Therapeutics, inc. and Amplyx, Research Funding–Karius and Shire. SK: Research funding: Humanigen, Tolero, Lentigen. Patents and Royalites: Novartis. DM: Scientific Advisory Board: Janssen, Honoraria: Seattle Genetics, Roche/Genentech, Research Funding: Juno Therapeutics, GlaxoSmithKline. MAK: Consultant–Pharmacyclics, Speaker–Incyte Corp, Seattle Genetics and Alexion Pharmaceuticals. EJ: Scientific Advisory Boards–Novartis. Speaker: Medison. AB: Scientific Advisory Boards–Novartis, Roche, Sanofi, Jazz, Adienne, Pfizer, Amgen. Research Funding: Novartis, Amgen, Takeda, Astellas, Celgene, Pfizer. JFD: Ownership/Equity–WUGEN. DLP: Research Funding–Novartis, Scientific Advisory Boards - Novartis, Kite, Patent and Royalty payments–Novartis. SIG: Research Funding–Novartis; Tmunity Therapeutics. Scientific Advisory Boards–Aileron; Fate Therapeutics; Intellia. Patent and Royalties–Novartis. Ownership/equity–Carisma Therapeutics. MS: Research Funding: Fate Theapeutics Inc, Consultant/Board of Director/Scientific Advisory Board/Patents and Royalties/Research Funding: Juno Therapeutics, MM: Lecture honoraria and Consultant- Novartis, Amgen and Pfizer. SKH: Honorarium: Mallinckrodt

Figures

**Fig. 1**
Indications for referral to center performing CAR-T therapy for evaluation of relapsed/refractory ALL

**Fig. 2**
Recommended timing to stop therapies prior to leukapheresis. (GVHD graft versus host disease, CNS central nervous system)

See this image and copyright information in PMC

Republished from

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.
Kansagra AJ, Frey NV, Bar M, Laetsch TW, Carpenter PA, Savani BN, Heslop HE, Bollard CM, Komanduri KV, Gastineau DA, Chabannon C, Perales MA, Hudecek M, Aljurf M, Andritsos L, Barrett JA, Bachanova V, Bonini C, Ghobadi A, Gill SI, Hill J, Kenderian S, Kebriaei P, Nagler A, Maloney D, Liu HD, Shah NN, Kharfan-Dabaja MA, Shpall EJ, Mufti GJ, Johnston L, Jacoby E, Bazarbachi A, DiPersio JF, Pavletic SZ, Porter DL, Grupp SA, Sadelain M, Litzow MR, Mohty M, Hashmi SK. Kansagra AJ, et al. Biol Blood Marrow Transplant. 2019 Mar;25(3):e76-e85. doi: 10.1016/j.bbmt.2018.12.068. Epub 2018 Dec 18. Biol Blood Marrow Transplant. 2019. PMID: 30576834 Free PMC article.

References

1. June CH, Sadelain M. Chimeric antigen receptor therapy. N Engl J Med. 2018;379:64–73. doi: 10.1056/NEJMra1706169. - DOI - PMC - PubMed
1. Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in children and young adults with B-Cell lymphoblastic leukemia. N Engl J Med. 2018;378:439–48. doi: 10.1056/NEJMoa1709866. - DOI - PMC - PubMed
1. Maus MV, Nikiforow S. The why, what, and how of the new FACT standards for immune effector cells. J Immunother Cancer. 2017;5:36. doi: 10.1186/s40425-017-0239-0. - DOI - PMC - PubMed
1. Das Rajat SJ, Barrett D. T cell dysfunction in pediatric cancer patients at diagnosis and after chemotherapy can limit chimeric antigen receptor potential. Cancer Res. 2018;2018(78 (13 suppl)):Abstract nr 1631.
1. Mejstrikova E, Hrusak O, Borowitz MJ, Whitlock JA, Brethon B, Trippett TM, et al. CD19-negative relapse of pediatric B-cell precursor acute lymphoblastic leukemia following blinatumomab treatment. Blood Cancer J. 2017;7:659. doi: 10.1038/s41408-017-0023-x. - DOI - PMC - PubMed

Grants and funding

LinkOut - more resources

Full Text Sources

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Clinical utilization of Chimeric Antigen Receptor T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL)-an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplantation (ASBMT)

Affiliations

Clinical utilization of Chimeric Antigen Receptor T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL)-an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplantation (ASBMT)

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

Republished from

References

Grants and funding

LinkOut - more resources

Full Text Sources