Neurologic adverse events of cancer immunotherapy

Marcelo Houat de Brito

doi:10.1590/0004-282X-ANP-2022-S116

Arquivos de Neuro-Psiquiatria, Inhaltsverzeichnis

CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2022; 80(S 05): 270-280
DOI: 10.1590/0004-282X-ANP-2022-S116

NEURO-ONCOLOGY

Neurologic adverse events of cancer immunotherapy

Eventos adversos neurológicos da imunoterapia contra o câncer

Marcelo Houat de Brito

¹Universidade de São Paulo, Hospital das Clinicas, Departamento de Neurologia, São Paulo SP, Brazil.

²Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, Departamento de Neurologia, Sao Paulo SP, Brazil.

› Institutsangaben

Abstract

ABSTRACT

Cancer immunotherapy encompasses a wide range of treatment modalities that harness the anti-tumor effects of the immune system and have revolutionized oncological treatment in recent years, with approval for its use in more and more cancers. However, it is not without side effects. Several neurological adverse events have been recognized associated with immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T-cell therapy, the two main classes of cancer immunotherapy. With the increase in the prevalence of oncological diseases and this type of therapy, it is improbable that neurologists, oncologists, hematologists, and other healthcare professionals who deal with cancer patients will not encounter this type of neurologic complication in their practice in the following years. This article aims to review the epidemiology, clinical manifestations, diagnosis, and management of neurological complications associated with ICI and CAR T-cell therapy.

RESUMO

A imunoterapia contra o câncer engloba uma gama de modalidades de tratamento que aumentam os efeitos antitumorais do próprio sistema imunológico do paciente e revolucionaram o tratamento oncológico nos últimos anos, com aprovação para seu uso em cada vez mais neoplasias. No entanto, não é sem efeitos colaterais. Vários eventos adversos neurológicos foram reconhecidos associados aos inibidores de checkpoint imunológico (ICI) e à terapia de células T com receptor de antígeno quimérico (CAR-T), as duas principais classes de imunoterapia contra o câncer. Com o aumento da prevalência de doenças oncológicas e desse tipo de terapia, é improvável que neurologistas, oncologistas, hematologistas e demais profissionais de saúde que lidam com pacientes com câncer não encontrem esse tipo de complicação neurológica em sua prática nos próximos anos. Este artigo tem como objetivo revisar a epidemiologia, as manifestações clínicas, o diagnóstico e o manejo das complicações neurológicas associadas à terapia com ICI e células CAR-T

Keywords:

Immune Checkpoint Inhibitors - Immunotherapy, Adoptive - Drug-Related Side Effects and Adverse Reactions - Neurologic Manifestations - Neuromuscular Diseases

Palavras-chave:

Inibidores de Checkpoint Imunológico - Imunoterapia Adotiva - Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos - Manifestações Neurológicas - Doenças Neuromusculares

Volltext

Referenzen

References
1 GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392 10159 1789-1858 https://doi.org/10.1016/S0140-6736(18)32279-7
2 Alatrash G, Jakher H, Stafford PD, Mittendorf EA. Cancer immunotherapies, their safety and toxicity. Expert Opin Drug Saf 2013; 12 (05) 631-645 https://doi.org/10.1517/14740338.2013.795944
3 Roth P, Winklhofer S, Müller AMS, Dummer R, Mair MJ, Gramatzki D. et al. Neurological complications of cancer immunotherapy. Cancer Treat Rev 2021; 97: 102189-102189 https://doi.org/10.1517/14740338.2013.795944
4 Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science 2018; 359 6382 1350-1355 https://doi.org/10.1126/science.aar4060
5 Graus F, Dalmau J. Paraneoplastic neurological syndromes in the era of immune-checkpoint inhibitors. Nat Rev Clin Oncol 2019; 16 (09) 535-548 https://doi.org/10.1038/s41571-019-0194-4
6 Twomey JD, Zhang B. Cancer immunotherapy update: FDA-Approved checkpoint inhibitors and companion diagnostics. AAPS J 2021; 23 (02) 39-39 https://doi.org/10.1208/s12248-021-00574-0
7 Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med 2018; 378 (02) 158-168 https://doi.org/10.1056/NEJMra1703481
8 Haanen JBAG, Carbonnel F, Robert C, Kerr KM, Peters S, Larkin J. et al. Management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017; 28 (Suppl. 04) iv119-iv142 https://doi.org/10.1093/annonc/mdx225
9 Cuzzubbo S, Javeri F, Tissier M, Roumi A, Barlog C, Doridam J. et al. Neurological adverse events associated with immune checkpoint inhibitors: review of the literature. Eur J Cancer 2017; 73: P1-8 https://doi.org/10.1016/j.ejca.2016.12.001
10 Marini A, Bernardini A, Gigli GL, Valente M, Muñiz-Castrillo S, Honnorat J. et al. Neurologic Adverse Events of Immune Checkpoint Inhibitors. Neurology 2021; 96 (16) 754-766 https://doi.org/10.1212/WNL.2022s1160000011795
11 Sato K, Mano T, Iwata A, Toda T. Neurological and related adverse events in immune checkpoint inhibitors: a pharmacovigilance study from the Japanese Adverse Drug Event Report database. J Neurooncol 2019; 145 (01) 1-9 https://doi.org/10.1007/s11060-019-03273-1
12 Dubey D, David WS, Reynolds KL, Chute DF, Clement NF, Cohen JV. et al. Severe neurological toxicity of immune checkpoint inhibitors: growing spectrum. Ann Neurol 2020; 87 (05) 659-669 https://doi.org/10.1002/ana.25708
13 Martins F, Sofiya L, Sykiotis GP, Lamine F, Maillard M, Fraga M. et al. Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Nat Rev Clin Oncol 2019; 16 (09) 563-580 https://doi.org/10.1038/s41571-019-0218-0
14 Guo C-Y, Jiang S-C, Kuang Y-K, Hu H. Incidence of ipilimumab-related serious adverse events in patients with advanced cancer: a meta-analysis. J Cancer 2019; 10 (01) 120-130 https://doi.org/10.7150/jca.28120
15 Shi S, Jaoube JA, Kanwar R, Jin MC, Amorin A, Varanasi V. et al. Neurological adverse effects due to programmed death 1 (PD-1) inhibitors. J Neurooncol 2020; 148 (02) 291-297 https://doi.org/10.1007/s11060-020-03514-8
16 Oliveira MCB, de Brito MH, Simabukuro MM. Central nervous system demyelination associated with immune checkpoint inhibitors: review of the literature. Front Neurol 2020; 11: 538695-538695 https://doi.org/10.3389/fneur.2020.538695
17 Moreira A, Loquai C, Pföhler C, Kähler KC, Knauss S, Heppt MV. et al. Myositis and neuromuscular side-effects induced by immune checkpoint inhibitors. Eur J Cancer 2019; 106: P12-P23 https://doi.org/10.1016/j.ejca.2018.09.033
18 Johansen A, Christensen SJ, Scheie D, Højgaard JLS, Kondziella D. Neuromuscular adverse events associated with anti-PD-1 monoclonal antibodies. Neurology 2019; 92 (14) 663-674 https://doi.org/10.1212/WNL.2022s1162022s1167235
19 Bruna J, Argyriou AA, Anastopoulou GG, Alemany M, Nadal E, Kalofonou F. et al. Incidence and characteristics of neurotoxicity in immune checkpoint inhibitors with focus on neuromuscular events: experience beyond the clinical trials. J Peripher Nerv Syst 2020; 25 (02) 171-177 https://doi.org/10.1111/jns.12371
20 Lazaridis K, Tzartos SJ. Autoantibody Specificities in myasthenia gravis; Implications for improved diagnostics and therapeutics. Front Immunol 2020; 11: 212-212 https://doi.org/10.3389/fimmu.2020.00212
21 Nakatani Y, Tanaka N, Enami T, Minami S, Okazaki T, Komuta K. Lambert-eaton myasthenic syndrome caused by nivolumab in a patient with squamous cell lung cancer. Case Rep Neurol 2018; 10 (03) 346-352 https://doi.org/10.1159/000494078
22 Golnik KC, Pena R, Lee AG, Eggenberger ER. An ice test for the diagnosis of myasthenia gravis. Ophthalmology 1999; 106 (07) P1282-P1286 https://doi.org/10.1016/S0161-6420(99)00709-5
23 Jordan B, Benesova K, Hassel JC, Wick W, Jordan K. How we identify and treat neuromuscular toxicity induced by immune checkpoint inhibitors. ESMO Open 2021; 6 (06) 100317-100317 https://doi.org/10.1016/j.esmoop.2021.100317
24 Wu WK, Broman KK, Brownie ER, Kauffmann RM. Ipilimumab-induced guillain-barré syndrome presenting as dysautonomia: an unusual presentation of a rare complication of immunotherapy. J Immunother 2017; 40 (05) 196-199 https://doi.org/10.1097/CJI.2022s1162022s1160167
25 Gaudy-Marqueste C, Monestier S, Franques J, Cantais E, Richard M-A, Grob J-J. A severe case of ipilimumab-induced guillain-barré syndrome revealed by an occlusive enteric neuropathy: a differential diagnosis for ipilimumab-induced colitis. J Immunother 2013; 36 (01) 77-78 https://doi.org/10.1097/CJI.0b013e31827807dd
26 Hughes RA, Brassington R, Gunn AA, van Doorn PA. Corticosteroids for Guillain-Barré syndrome. Cochrane Database Syst Rev 2016; 10 (10) CD001446-CD001446 https://doi.org/10.1002/14651858.CD001446.pub5
27 Harrison RA, Tummala S, de Groot J. Neurologic toxicities of cancer immunotherapies: a review. Curr Neurol Neurosci Rep 2020; 20 (07) 27-27 https://doi.org/10.1007/s11910-020-01038-2
28 Kolb NA, Trevino CR, Waheed W, Sobhani F, Landry KK, Thomas AA. et al. Neuromuscular complications of immune checkpoint inhibitor therapy. Muscle Nerve 2018; 58 (01) 10-22 https://doi.org/10.1002/mus.26070
29 Abboud H, Probasco JC, Irani S, Ances B, Benavides DR, Bradshaw M. et al. Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management. J Neurol Neurosurg Psychiatry 2021; 92 (07) 757-768 https://doi.org/10.1136/jnnp-2020-325300
30 Shibaki R, Murakami S, Oki K, Ohe Y. Nivolumab-induced autoimmune encephalitis in an anti-neuronal autoantibody-positive patient. Jpn J Clin Oncol 2019; 49 (08) 793-794 https://doi.org/10.1093/jjco/hyz087
31 Vogrig A, Fouret M, Joubert B, Picard G, Rogemond V, Pinto A-L. et al. Increased frequency of anti-Ma2 encephalitis associated with immune checkpoint inhibitors. Neurol Neuroimmunol Neuroinflamm 2019; 6 (06) e604 https://doi.org/10.1212/NXI.2022s1162022s1160604
32 Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T. et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016; 15 (04) 391-404 https://doi.org/10.1016/S1474-4422(15)00401-9
33 Soror NN, Hemrock L, Shah P, Loges RJ, Tharu B. Brain stem encephalitis in a patient with recurrent small cell lung cancer treated with immune checkpoint inhibitor: case presentation and review of the literature. Cureus 2021; 13 (01) e13034 https://doi.org/10.7759/cureus.13034
34 Abboud H, Probasco J, Irani SR, Ances B, Benavides DR, Bradshaw M. et al. Autoimmune encephalitis: proposed recommendations for symptomatic and long-term management. J Neurol Neurosurg Psychiatry 2021; 92 (08) 897-907 https://doi.org/10.1136/jnnp-2020-325302
35 Yamout B, Al Khawajah M. Radiologically isolated syndrome and multiple sclerosis. Mult Scler Relat Disord 2017; 17: P234-P237 https://doi.org/10.1016/j.msard.2017.08.016
36 Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G. et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 2018; 17 (02) 162-173 https://doi.org/10.1016/S1474-4422(17)30470-2
37 Narumi Y, Yoshida R, Minami Y, Yamamoto Y, Takeguch S, Kano K. et al. Neuromyelitis optica spectrum disorder secondary to treatment with anti-PD-1 antibody nivolumab: the first report. BMC Cancer 2018; 18 (01) 95-95 https://doi.org/10.1186/s12885-018-3997-2
38 Shimada T, Hoshino Y, Tsunemi T, Hattori A, Nakagawa E, Yokoyama K. et al. Neuromyelitis optica spectrum disorder after treatment with pembrolizumab. Mult Scler Relat Disord 2020; 37: 101447-101447 https://doi.org/10.1016/j.msard.2019.101447
39 Kemanetzoglou E, Andreadou E. CNS Demyelination with TNF-α Blockers. Curr Neurol Neurosci Rep 2017; 17 (04) 36-36 https://doi.org/10.1007/s11910-017-0742-1
40 Lesage C, Longvert C, Prey S, Maanaoui S, Dréno B, Machet L. et al. Incidence and clinical impact of Anti-TNFα treatment of severe immune checkpoint inhibitor-induced colitis in advanced melanoma: the mecolit survey. J Immunother 2019; 42 (05) 175-179 https://doi.org/10.1097/CJI.2022s1162022s1160268
41 Dalmau J, Rosenfeld MR. Paraneoplastic syndromes of the CNS. Lancet Neurol 2008; 7 (04) 327-340 https://doi.org/10.1016/S1474-4422(08)70060-7
42 Sznol M, Postow MA, Davies MJ, Pavlick AC, Plimack ER, Shaheen M. et al. Endocrine-related adverse events associated with immune checkpoint blockade and expert insights on their management. Cancer Treat Rev 2017; 58: P70-P76 https://doi.org/10.1016/j.ctrv.2017.06.002
43 Min L, Hodi FS, Giobbie-Hurder A, Ott PA, Luke JJ, Donahue H. et al. Systemic high-dose corticosteroid treatment does not improve the outcome of ipilimumab-related hypophysitis: a retrospective cohort study. Clin Cancer Res 2015; 21 (04) 749-755 https://doi.org/10.1158/1078-0432.CCR-14-2353
44 Puzanov I, Diab A, Abdallah K, Bingham CO, Brogdon C, Dadu R. et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer 2017; 5 (01) 95-95 https://doi.org/10.1186/s40425-017-0300-z
45 June CH, Sadelain M. Chimeric antigen receptor therapy. N Engl J Med 2018; 379 (01) 64-73 https://doi.org/10.1056/NEJMra1706169
46 Santomasso BD. Anticancer drugs and the nervous system. Continuum (Minneap Minn). 2020; 26 (03) 732-764 https://doi.org/10.1212/CON.2022s1162022s1160873
47 First-ever CAR T-cell Therapy Approved in U.S.. Cancer Discov. 2017 Oct 1;7(10):OF1. https://doi.org/10.1158/2159-8290.CD-NB2017-126
48 National Cancer Institute. CAR T Cells: Engineering patients’ immune cells to treat their cancers [Internet]. 2022. modified 2022 Mar 10 2022 Mar 13 Available from: https://www.cancer.gov/about-cancer/treatment/research/car-t-cells#:~:text=Since%202017%2C%20six%20CAR%20T,%2C%20most%20recently%2C%20multiple%20myeloma
49 Santomasso B, Bachier C, Westin J, Rezvani K, Shpall EJ. The Other Side of CAR T-Cell Therapy: Cytokine Release Syndrome, Neurologic Toxicity, and Financial Burden. Am Soc Clin Oncol Educ Book 2019; 39: 433-444 https://doi.org/10.1200/EDBK_238691
50 Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN. et al. ASTCT Consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant 2019; 25 (04) P625-P638 https://doi.org/10.1016/j.bbmt.2018.12.758
51 Shimabukuro-Vornhagen A, Gödel P, Subklewe M, Stemmler HJ, Schlößer HA, Schlaak M. et al. Cytokine release syndrome. J Immunother Cancer 2018; 6 (01) 56-56 https://doi.org/10.1186/s40425-018-0343-9
52 Sievers S, Watson G, Johncy S, Adkins S. Recognizing and grading CAR T-Cell toxicities: an advanced practitioner perspective. Front Oncol 2020; 10: 885-885 https://doi.org/10.3389/fonc.2020.00885
53 Zhou X, Rasche L, Kortüm KM, Danhof S, Hudecek M, Einsele H. Toxicities of chimeric antigen receptor T Cell therapy in multiple myeloma: an overview of experience from clinical trials, pathophysiology, and management strategies. Front Immunol 2020; 11: 620312-620312 https://doi.org/10.3389/fimmu.2020.620312
54 Topp MS, Gökbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC. et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol 2015; 16 (01) P57-P66 https://doi.org/10.1016/S1470-2045(14)71170-2
55 Rubin DB, Danish HH, Ali AB, Li K, LaRose S, Monk AD. et al. Neurological toxicities associated with chimeric antigen receptor T-cell therapy. Brain 2019; 142 (05) 1334-1348 https://doi.org/10.1093/brain/awz053
56 Gust J, Hay KA, Hanafi L-A, 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; 7 (12) 1404-1419 https://doi.org/10.1158/2159-8290.CD-17-0698
57 Santomasso BD, Park JH, Salloum D, Riviere I, Flynn J, Mead E. et al. Clinical and biological correlates of neurotoxicity associated with CAR T-cell therapy in patients with B-cell acute lymphoblastic leukemia. Cancer Discov 2018; 8 (08) 958-971 https://doi.org/10.1158/2159-8290.CD-17-1319
58 Norelli M, Camisa B, Barbiera G, Falcone L, Purevdorj A, Genua M. et al. Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells. Nat Med 2018; 24 (06) 739-748 https://doi.org/10.1038/s41591-018-0036-4
59 Johnsrud A, Craig J, Baird J, Spiegel J, Muffly L, Zehnder J. et al. Incidence and risk factors associated with bleeding and thrombosis following chimeric antigen receptor T-cell therapy. Blood Adv 2021; 5( (21) 4465-4475 https://doi.org/10.1182/bloodadvances.2021004716
60 Neill L, Rees J, Roddie C. Neurotoxicity-CAR T-cell therapy: what the neurologist needs to know. Pract Neurol 2020; 20 (04) 285-293 https://doi.org/10.1136/practneurol-2020-002550
61 Yoon JG, Smith DA, Tirumani SH, Caimi PF, Ramaiya NH. CAR T-Cell therapy: an update for radiologists. AJR Am J Roentgenol 2021; 217 (06) 1461-1474 https://doi.org/10.2214/AJR.21.26091
62 Yakoub-Agha I, Chabannon C, Bader P, Basak GW, Bonig H, Ciceri F. et al. Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE). Haematologica 2020; 105 (02) 297-316 https://doi.org/10.3324/haematol.2019.229781