Clinical presentation, management, and biomarkers of neurotoxicity after adoptive immunotherapy with CAR T cells.

Blood
Philipp KarschniaJorg Dietrich

Abstract

Chimeric antigen receptor (CAR) T cells have emerged as a promising class of cell-based immunotherapy in refractory malignancies. Neurotoxicity represents a common and potentially life-threatening adverse effect of CAR T cells, and clinical experience is limited. Here, we describe the clinical presentation and management of 25 adult patients who presented with neurotoxic syndromes after CAR T-cell therapy at the Massachusetts General Hospital. This cohort includes 24 patients treated with CD19-directed CAR T cells for non-Hodgkin lymphoma (n = 23) and acute lymphoblastic leukemia (n = 1), and 1 patient treated with α-fetoprotein-directed CAR T cells for hepatocellular carcinoma (n = 1). Twelve of the 25 patients (48%) developed grade 1-2 neurotoxicity and 13 patients (52%) presented with grade 3-4 neurotoxicity. We found that lower platelet counts at time of CAR T-cell infusion were associated with more severe neurotoxicity (P = .030). Cytokine release syndrome occurred in 24 of 25 patients (96%). Serum levels of ferritin peaked with onset of neurologic symptoms, and higher ferritin levels were associated with higher neurotoxicity grade. Grade 3-4 neurotoxicity correlated negatively with overall survival (OS) (P = .013). Median...Continue Reading

References

Aug 13, 2011·The New England Journal of Medicine·David L PorterCarl H June
Mar 27, 2013·The New England Journal of Medicine·Stephan A GruppCarl H June
Feb 21, 2014·Science Translational Medicine·Marco L DavilaRenier Brentjens
Aug 27, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·James N KochenderferSteven A Rosenberg
Oct 16, 2014·The New England Journal of Medicine·Shannon L MaudeStephan A Grupp
May 22, 2016·Blood·Jennifer N Brudno, James N Kochenderfer
May 26, 2017·Nature·Michel SadelainStanley Riddell
Sep 20, 2017·Nature Reviews. Clinical Oncology·Sattva S NeelapuElizabeth J Shpall
Dec 7, 2017·Cancer Discovery·Crystal L Mackall, David B Miklos
Dec 12, 2017·The New England Journal of Medicine·Sattva S NeelapuWilliam Y Go
Jan 13, 2018·Scientific Reports·Christopher DalySamuel Davis
Feb 1, 2018·The New England Journal of Medicine·Jae H ParkMichel Sadelain
Feb 13, 2018·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Hongfei JiQingyuan Zhang
Feb 13, 2018·Nature Reviews. Clinical Oncology·David T TeacheyStephan A Grupp
Mar 23, 2018·Cancer Discovery·Agne TaraseviciuteMichael C Jensen
Jul 1, 2018·Neurology·Aline HerlopianMichael B Westover
Jul 5, 2018·The New England Journal of Medicine·Carl H June, Michel Sadelain
Sep 5, 2018·Annals of Neurology·Jacqueline S GofshteynJennifer L McGuire

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Citations

Jul 30, 2019·Immunological Reviews·Joseph H OvedDavid T Teachey
Jul 20, 2019·Blood·Matthew J FrigaultMarcela V Maus
Nov 22, 2019·Leukemia & Lymphoma·Kirk E CahillPeter A Riedell
Aug 27, 2019·Current Opinion in Oncology·Erin M Gibson, Michelle Monje
Jan 23, 2020·Cancer·L Nicolas Gonzalez Castro, Tracey A Milligan
Feb 23, 2020·Critical Care Nursing Quarterly·Amanda M RiveraMegan E Barra
Apr 10, 2020·Blood Advances·Adrian H J TanDario Campana
Dec 18, 2019·Briefings in Functional Genomics·Guillermo Ureña-BailénMarkus Mezger
May 10, 2020·Pharmacotherapy·Craig W Freyer, David L Porter
Aug 11, 2020·JAMA Neurology·Daniel B RubinHenrikas Vaitkevicius
Aug 19, 2020·Immunotherapy·Ajeet GajraBruce A Feinberg
Apr 9, 2020·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Á Rodríguez PérezD Benítez-Ribas
Jul 2, 2020·Current Oncology Reports·Kara Landry, Alissa A Thomas
Apr 3, 2020·The Journal of Clinical Investigation·Matthew J Frigault, Marcela V Maus
Dec 31, 2019·Journal of Hematology & Oncology·Lauren C FleischerSunil S Raikar
Jul 17, 2020·Frontiers in Oncology·Savannah SieversSherry Adkins
Oct 23, 2019·Signal Transduction and Targeted Therapy·Dan LiWei Wang
Apr 26, 2020·Clinical and Experimental Medicine·Stefan LundhJoseph A Fraietta
Jun 7, 2020·Practical Neurology·Lorna NeillClaire Roddie
Sep 18, 2020·Current Opinion in Neurology·Sebastian F WinterJorg Dietrich
Dec 19, 2020·Journal for Immunotherapy of Cancer·Marcela V MausStephan A Grupp
Jan 13, 2021·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Patrick M Reagan, Sattva S Neelapu
Aug 11, 2020·Annual Review of Medicine·Andrea SchmidtsMarcela V Maus
Nov 2, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Mark B LeickMatthew J Frigault
Dec 5, 2020·Continuum : Lifelong Learning in Neurology·Jorg Dietrich
Nov 6, 2020·Scientific Reports·Catherine BelinAntoine F Carpentier
Jan 23, 2021·Transfusion and Apheresis Science : Official Journal of the World Apheresis Association : Official Journal of the European Society for Haemapheresis·Joseph M GrimesPawel Muranski
Dec 19, 2019·Journal of Clinical Neurophysiology : Official Publication of the American Electroencephalographic Society·Juliane GustXiuhua Bozarth
Mar 9, 2021·BMJ Neurology Open·Elisaveta SokolovJorg Dietrich

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