Clinical and biological correlates of neurotoxicity associated with car t-cell therapy in patients with B-cell acute lymphoblastic leukemia

Cancer Discovery

Volumn 8, Issue 8, 2018, Pages 958-971

  Santomasso, Bianca D ^a,b   Park, Jae H ^a,c   Salloum, Darin ^a   Riviere, Isabelle ^a   Flynn, Jessica ^a   Mead, Elena ^a   Halton, Elizabeth ^a   Wang, Xiuyan ^a   Senechal, Brigitte ^a   Purdon, Terence ^a   Cross, Justin R ^a   Liu, Hui ^a   Vachha, Behroze ^a   Chen, Xi ^a   Deangelis, Lisa M ^a   Li, Daniel ^d   Bernal, Yvette ^a   Gonen, Mithat ^a   Wendel, Hans Guido ^a   Sadelain, Michel ^a   Brentjens, Renier J ^a,c   more..

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b PARKER INSTITUTE FOR CANCER IMMUNOTHERAPY   (United States)

^c WEILL CORNELL MEDICAL COLLEGE   (United States)

^d Juno Therapeutics   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD19 ANTIGEN; CORTICOSTEROID; CYCLOPHOSPHAMIDE; FLUDARABINE; GAMMA INTERFERON INDUCIBLE PROTEIN 10; INTERLEUKIN 6; INTERLEUKIN 8; MONOCYTE CHEMOTACTIC PROTEIN 1; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; TOCILIZUMAB; CD19 MOLECULE, HUMAN; CYTOKINE; LYMPHOCYTE ANTIGEN RECEPTOR; MONOCLONAL ANTIBODY;

ACUTE BRAIN DISEASE; ACUTE LYMPHOBLASTIC LEUKEMIA; ADULT; ARTICLE; ATAXIC APHASIA; BLOOD CEREBROSPINAL FLUID BARRIER; BODY MASS; BODY WEIGHT; CHIMERIC ANTIGEN RECEPTOR T-CELL IMMUNOTHERAPY; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CYTOKINE RELEASE; DISEASE BURDEN; DISEASE SEVERITY; ELECTROENCEPHALOGRAPHY; FEMALE; HEADACHE; HUMAN; IMMUNE RESPONSE; INFLAMMATION; LEUKOCYTE COUNT; LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY; MAJOR CLINICAL STUDY; MALE; MYOCLONUS; NEUROIMAGING; NEUROTOXICITY; NUCLEAR MAGNETIC RESONANCE IMAGING; PHASE 1 CLINICAL TRIAL; SEIZURE; ADOPTIVE TRANSFER; ADVERSE EVENT; BLOOD; CEREBROSPINAL FLUID; CLINICAL TRIAL; DIAGNOSTIC IMAGING; IMMUNOLOGY; METABOLISM; MIDDLE AGED; PATHOLOGY; PROCEDURES; T LYMPHOCYTE; TOXICITY AND INTOXICATION; TRANSPLANTATION; TUMOR VOLUME; YOUNG ADULT;

ADOPTIVE TRANSFER; ADRENAL CORTEX HORMONES; ADULT; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTIGENS, CD19; CYTOKINES; FEMALE; HUMANS; MAGNETIC RESONANCE IMAGING; MALE; MIDDLE AGED; NEUROIMAGING; NEUROTOXICITY SYNDROMES; PRECURSOR B-CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; RECEPTORS, ANTIGEN, T-CELL; T-LYMPHOCYTES; TUMOR BURDEN; YOUNG ADULT;

EID: 85052999490     PISSN: 21598274     EISSN: 21598290     Source Type: Journal    
DOI: 10.1158/2159-8290.CD-17-1319     Document Type: Article

References (49)

1. Brentjens RJ, Davila ML, Riviere I, Park J, Wang X, Cowell LG, et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med 2013;5:177ra38.
2. Park JH, Geyer MB, Brentjens RJ. CD19-targeted CAR T-cell therapeutics for hematologic malignancies: interpreting clinical outcomes to date. Blood 2016;127:3312–20.
3. Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 2014;371:1507–17.
4. + composition in adult B cell ALL patients. J Clin Invest 2016;126:2123–38.
5. Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet 2015;385:517–28.
6. Gardner RA, Finney O, Annesley C, Brakke H, Summers C, Leger K, et al. Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood 2017;129:3322–31.
7. Kochenderfer JN, Somerville RPT, Lu T, Shi V, Bot A, Rossi J, et al. Lymphoma remissions caused by anti-CD19 chimeric antigen receptor T cells are associated with high serum interleukin-15 levels. J Clin Oncol 2017;35:1803–13.
8. Park JH, Riviere I, Gonen M, Wang X, Senechal B, Curran KJ, et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med 2018;378:449–59.
9. Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med 2017;377:2531–44.
10. Mueller KT, Maude SL, Porter DL, Frey N, Wood P, Han X, et al. Cellular kinetics of CTL019 in relapsed/refractory B-cell acute lymphoblastic leukemia and chronic lymphocytic leukemia. Blood 2017;130:2317–25.
11. Gust J, Hay KA, Hanafi LA, Li D, Myerson D, Gonzalez-Cuyar LF, et al. Endothelial activation and blood-brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 CAR-T cells. Cancer Discov 2017.
12. Frey NV, Levine BL, Lacey SF, Grupp SA, Maude SL, Schuster SJ, et al. Refractory cytokine release syndrome in recipients of chimeric antigen receptor (CAR) T cells. Blood 2014;124:2296.
13. Brudno JN, Kochenderfer JN. Toxicities of chimeric antigen receptor T cells: recognition and management. Blood 2016;127:3321–30.
14. Gilbert MJ. Severe neurotoxicity in the phase 2 trial of JCAR015 in adult B-ALL (ROCKET Study): analyses of patient, protocol and product attributes. Presented at 2017 SITC Annual Meeting, Session 102, 2017.
15. Locke FL, Neelapu SS, Bartlett NL, Lekakis LJ, Jacobson CA, Braun-schweig I, et al. Preliminary results of prophylactic tocilizumab after axicabtageneciloleucel (axi-cel; KTE-C19) treatment for patients with refractory, aggressive non-Hodgkin lymphoma (NHL). Blood (ASH Abstract) 2017;130:1547.
16. Taraseviciute A, Tkachev V, Ponce R, Turtle CJ, Snyder JM, Liggitt HD, et al. Chimeric antigen receptor T cell-mediated neurotoxicity in non-human primates. Cancer Discov 2018;8:750–63.
17. Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, et al. Chimeric antigen receptor T-cell therapy – assessment and management of toxicities. Nat Rev Clin Oncol 2018;15:47–62.
18. Ben-Ezra J, Sheibani K, Hwang DL, Lev-Ran A. Megakaryocyte synthesis is the source of epidermal growth factor in human platelets. Am J Pathol 1990;137:755–9.
19. Hay KA, Hanafi LA, Li D, Gust J, Liles WC, Wurfel MM, et al. Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy. Blood 2017;130:2295–306.
20. Higgins SJ, Purcell LA, Silver KL, Tran V, Crowley V, Hawkes M, et al. Dysregulation of angiopoietin-1 plays a mechanistic role in the pathogenesis of cerebral malaria. Sci Transl Med 2016;8:358ra128.
21. Reiber H. Flow rate of cerebrospinal fluid (CSF)–a concept common to normal blood-CSF barrier function and to dysfunction in neurological diseases. J Neurol Sci 1994;122:189–203.
22. Fry TJ, Shah NN, Orentas RJ, Stetler-Stevenson M, Yuan CM, Ramakrishna S, et al. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat Med 2018;24:20–8.
23. Cooley S, He F, Bachanova V, Vercellotti GM, DeFor TE, Curtsinger J, et al. Neurological consequences of cytokine release syndrome following subcutaneous recombinant IL-15 and haploidentical donor natural killer cell therapy for advanced acute myeloid leukemia. Blood (ASH Abstract) 2017;130:2649.
24. Wassmann S, Stumpf M, Strehlow K, Schmid A, Schieffer B, Bohm M, et al. Interleukin-6 induces oxidative stress and endothelial dysfunction by overexpression of the angiotensin II type 1 receptor. Circ Res 2004;94:534–41.
25. Esteve E, Castro A, Lopez-Bermejo A, Vendrell J, Ricart W, Fernandez-Real JM. Serum interleukin-6 correlates with endothelial dysfunction in healthy men independently of insulin sensitivity. Diabetes Care 2007;30:939–45.
26. Gardner R, Leger KJ, Annesley CE, Summers C, Rivers J, Gust J, et al. Decreased rates of severe CRS seen with early intervention strategies for CD19 CAR-T cell toxicity management. Blood (ASH Abstract) 2016;128:586.
27. Nishimoto N, Terao K, Mima T, Nakahara H, Takagi N, Kakehi T. Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood 2008;112:3959–64.
28. Brouwers J, Noviyanti R, Fijnheer R, de Groot PG, Trianty L, Mudaliana S, et al. Platelet activation determines angiopoietin-1 and VEGF levels in malaria: implications for their use as biomarkers. PLoS One 2014;8:e64850.
29. Granata G, Greco A, Iannella G, Granata M, Manno A, Savastano E, et al. Posterior reversible encephalopathy syndrome–Insight into pathogenesis, clinical variants and treatment approaches. Autoimmun Rev 2015;14:830–6.
30. Morishima T, Togashi T, Yokota S, Okuno Y, Miyazaki C, Tashiro M, et al. Encephalitis and encephalopathy associated with an influenza epidemic in Japan. Clin Infect Dis 2002;35:512–7.
31. McKinney AM, Jagadeesan BD, Truwit CL. Central-variant posterior reversible encephalopathy syndrome: brainstem or basal ganglia involvement lacking cortical or subcortical cerebral edema. AJR Am J Roentgenol 2013;201:631–8.
32. Alvarenga RM, Neri VC, Mendonca T, Camargo S. Acute encephalopathy with bilateral thalamotegmental involvement and a benign course: a case report from Brazil. BMJ Case Rep 2011;2011.
33. Ishii N, Mochizuki H, Moriguchi-Goto S, Shintaku M, Asada Y, Taniguchi A, et al. An autopsy case of elderly-onset acute necrotiz-ing encephalopathy secondary to influenza. J Neurol Sci 2015;354: 129–30.
34. Brown CE, Alizadeh D, Starr R, Weng L, Wagner JR, Naranjo A, et al. Regression of glioblastoma after chimeric antigen receptor T-cell therapy. N Engl J Med 2016;375:2561–9.
35. Fuentes ME, Durham SK, Swerdel MR, Lewin AC, Barton DS, Megill JR, et al. Controlled recruitment of monocytes and macrophages to specific organs through transgenic expression of monocyte chemoattractant protein-1. J Immunol 1995;155:5769–76.
36. McManus CM, Weidenheim K, Woodman SE, Nunez J, Hesselgesser J, Nath A, et al. Chemokine and chemokine-receptor expression in human glial elements: induction by the HIV protein, Tat, and chemokine autoregulation. Am J Pathol 2000;156:1441–53.
37. Ehrlich LC, Hu S, Sheng WS, Sutton RL, Rockswold GL, Peterson PK, et al. Cytokine regulation of human microglial cell IL-8 production. J Immunol 1998;160:1944–8.
38. Zink MC, Coleman GD, Mankowski JL, Adams RJ, Tarwater PM, Fox K, et al. Increased macrophage chemoattractant protein-1 in cerebrospinal fluid precedes and predicts simian immunodeficiency virus encephalitis. J Infect Dis 2001;184:1015–21.
39. Heyes MP, Saito K, Major EO, Milstien S, Markey SP, Vickers JH. A mechanism of quinolinic acid formation by brain in inflammatory neurological disease. Attenuation of synthesis from L-tryptophan by 6-chlorotryptophan and 4-chloro-3-hydroxyanthranilate. Brain 1993;116:1425–50.
40. Pemberton LA, Kerr SJ, Smythe G, Brew BJ. Quinolinic acid production by macrophages stimulated with IFN-gamma, TNF-alpha, and IFN-alpha. J Interferon Cytokine Res 1997;17:589–95.
41. Schwarcz R, Brush GS, Foster AC, French ED. Seizure activity and lesions after intrahippocampal quinolinic acid injection. Exp Neurol 1984;84:1–17.
42. Lugo-Huitron R, Ugalde Muniz P, Pineda B, Pedraza-Chaverri J, Rios C, Perez-de la Cruz V. Quinolinic acid: an endogenous neu-rotoxin with multiple targets. Oxid Med Cell Longev 2013;2013: 104024.
43. Schiefer J, Topper R, Schmidt W, Block F, Heinrich PC, Noth J, et al. Expression of interleukin 6 in the rat striatum following stereotaxic injection of quinolinic acid. J Neuroimmunol 1998;89:168–76.
44. Guillemin GJ, Croitoru-Lamoury J, Dormont D, Armati PJ, Brew BJ. Quinolinic acid upregulates chemokine production and chemokine receptor expression in astrocytes. Glia 2003;41:371–81.
45. Tavares RG, Tasca CI, Santos CE, Alves LB, Porciuncula LO, Ema-nuelli T, et al. Quinolinic acid stimulates synaptosomal glutamate release and inhibits glutamate uptake into astrocytes. Neurochem Int 2002;40:621–7.
46. St’astny F, Skultetyova I, Pliss L, Jezova D. Quinolinic acid enhances permeability of rat brain microvessels to plasma albumin. Brain Res Bull 2000;53:415–20.
47. Marti-Masso JF, Bergareche A, Makarov V, Ruiz-Martinez J, Gorostidi A, Lopez de Munain A, et al. The ACMSD gene, involved in tryptophan metabolism, is mutated in a family with cortical myoclonus, epilepsy, and parkinsonism. J Mol Med (Berl) 2013;91:1399–406.
48. Clark IA, Vissel B. Excess cerebral TNF causing glutamate excito-toxicity rationalizes treatment of neurodegenerative diseases and neurogenic pain by anti-TNF agents. J Neuroinflammation 2016; 13:236.
49. Brentjens RJ, Riviere I, Park JH, Davila ML, Wang X, Stefanski J, et al. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood 2011;118:4817–28.