Immune Effector Cell associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS).

Mar 13, 2023

Experts: Melissa R Hines,Tristan E Knight,Kevin O McNerney,Mark B Leick,Tania Jain,Sairah Ahmed,Matthew J Frigault,Joshua A Hill,Michael D Jain,William T Johnson,Yi Lin,Kris M Mahadeo,Gabriela M Maron,Rebecca A Marsh,Sattva S Neelapu,Sarah Nikiforow,Amanda K Ombrello,Nirav N Shah,Aimee C Talleur,David Turicek,Anant Vatsayan,Sandy W Wong,Marcela V Maus,Krishna V Komanduri,Nancy Berliner,Jan-Inge Henter,Miguel-Angel Perales,Noelle V Frey,David T Teachey,Matthew J Frank,Nirali N Shah

T cell mediated hyperinflammatory responses such as cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) are now well-established toxicities of chimeric antigen receptor (CAR) T cells. As the field of CAR T cells advances, however, there is increasing recognition that hemophagocytic lymphohistiocytosis (HLH)-like toxicities following CAR T cell infusions are occurring broadly across patient populations and CAR T cell constructs. Importantly, these HLH-like toxicities are often not as directly associated with CRS and/or its severity as initially described. This emergent toxicity, however ill-defined, is associated with life-threatening complications, creating an urgent need for improved identification and optimal management.
With the goal to improve patient outcomes and formulate a framework to characterize and study this HLH-like syndrome, we established an American Society for Transplantation and Cellular Therapy (ASTCT) panel comprised of experts in primary and secondary HLH, pediatric and adult HLH, infectious disease, rheumatology and hematology, oncology, and cellular therapy.
Through this effort, we provide an overview of the underlying biology of classical primary and secondary HLH, its relationship with similar manifestations following CAR T cell infusions and propose the term “immune effector cell (IEC) associated HLH-like syndrome (IEC-HS)” to describe this emergent toxicity. Further, we delineate a framework for identification of IEC-HS and put forward a grading schema which can be used to assess severity and facilitate cross-trial comparisons. Additionally, given the critical need to optimize outcomes for patients experiencing IEC-HS, we provide insights into potential treatment approaches, strategies to optimize supportive care and delineate alternate etiologies which should be considered in a patient presenting with IEC-HS.
By collectively defining IEC-HS as a hyperinflammatory toxicity we can now embark on further study of the pathophysiology underlying this toxicity profile and make strides towards a more comprehensive assessment and treatment approach.

Copyright © 2023. Published by Elsevier Inc.

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ABOUT THE EXPERTS

Melissa R Hines,Tristan E Knight,Kevin O McNerney,Mark B Leick,Tania Jain,Sairah Ahmed,Matthew J Frigault,Joshua A Hill,Michael D Jain,William T Johnson,Yi Lin,Kris M Mahadeo,Gabriela M Maron,Rebecca A Marsh,Sattva S Neelapu,Sarah Nikiforow,Amanda K Ombrello,Nirav N Shah,Aimee C Talleur,David Turicek,Anant Vatsayan,Sandy W Wong,Marcela V Maus,Krishna V Komanduri,Nancy Berliner,Jan-Inge Henter,Miguel-Angel Perales,Noelle V Frey,David T Teachey,Matthew J Frank,Nirali N Shah

Melissa R Hines

Department of Pediatric Medicine, Division of Critical Care, St Jude Children’s Research Hospital, Memphis, TN.

Tristan E Knight

Pediatric Hematology and Oncology, Seattle Children’s Hospital and the University of Washington School of Medicine, Seattle, WA.

Kevin O McNerney

Cancer and Blood Disorders Institute, Johns Hopkins All Children’s Hospital, St. Petersburg, FL.

Mark B Leick

Cellular Immunotherapy Program and Blood and Marrow Transplant Program, Cancer Center, Massachusetts General Hospital, Boston, MA.

Tania Jain

Division of Hematological Malignancies and Bone Marrow Transplantation, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD.

Sairah Ahmed

Departments of Lymphoma and Myeloma and Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX.

Matthew J Frigault

Cellular Immunotherapy Program and Blood and Marrow Transplant Program, Cancer Center, Massachusetts General Hospital, Boston, MA.

Joshua A Hill

Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Center, Seattle, WA.

Michael D Jain

Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL.

William T Johnson

Department of Medicine, Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY.

Yi Lin

Division Hematology-Oncology and Blood and Marrow Transplantation Program, Mayo Clinic, Rochester, MN.

Kris M Mahadeo

Pediatric Transplantation and Cellular Therapy, Duke University, Durham, NC.

Gabriela M Maron

Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN, and Department of Pediatrics, University of Tennessee Health Science Center College of Medicine.

Rebecca A Marsh

University of Cincinnati, and Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH.

Sattva S Neelapu

Departments of Lymphoma and Myeloma and Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX.

Sarah Nikiforow

Division of Hematologic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.

Amanda K Ombrello

Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD.

Nirav N Shah

Bone Marrow Transplant and Cellular Therapy Program, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI.

Aimee C Talleur

Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children’s Research Hospital, Memphis, TN and Department of Pediatrics, University of Tennessee Health Science Center College of Medicine.

David Turicek

Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Anant Vatsayan

Division of Blood and Marrow Transplantation, Children’s National Health System, Washington, DC.

Sandy W Wong

UCSF Health Division of Hematology and Oncology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.

Marcela V Maus

Cellular Immunotherapy Program and Blood and Marrow Transplant Program, Cancer Center, Massachusetts General Hospital, Boston, MA.

Krishna V Komanduri

UCSF Health Division of Hematology and Oncology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.

Nancy Berliner

Brigham and Women’s Hospital, Boston, MA.

Jan-Inge Henter

Division of Pediatric Oncology and Surgery, Department of Women’s and Children’s Health, Karolinska Institute, and Department of Paediatric Oncology, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden.

Miguel-Angel Perales

Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY.

Noelle V Frey

Division of Hematology-Oncology, Abramson Cancer Center and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.

David T Teachey

Division of Oncology, The Children’s Hospital of Philadelphia, Philadelphia, PA.

Matthew J Frank

Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA.

Nirali N Shah

Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD. Electronic address: Nirali.Shah@nih.gov.