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Published in: Clinical and Translational Oncology 10/2019

01-10-2019 | Multiple Sclerosis | Research Article

Multiple sclerosis outcomes after cancer immunotherapy

Authors: Catherine R. Garcia, Rani Jayswal, Val Adams, Lowell B. Anthony, John L. Villano

Published in: Clinical and Translational Oncology | Issue 10/2019

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Abstract

Introduction

Neurological immune-related adverse events are a rare but potentially deadly complication after immune checkpoint inhibitor (ICI) treatment. As multiple sclerosis (MS) is an immune-mediated disease, it is unknown how ICI treatment may affect outcomes.

Methods

We analyzed the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, ipilimumab, avelumab, and durvalumab 2 years prior their FDA approval until December 31, 2017, to include all cases with confirmed diagnosis/relapse of MS. We also included cases reported in the literature and a patient from our institution.

Results

We identified 14 cases of MS with median age of presentation of 52 years. Indications for ICI included melanoma in 7 (36.36%) cases, non-small cell lung carcinoma in 2 (18.18%) cases, 1 case (9.09%) each of pleural mesothelioma, renal cell carcinoma, and colorectal cancer, and unreported in 2 (18.18%) cases. History of MS was confirmed in 8 (57.1%) cases. Median time to beginning of symptoms was 29 days with rapid disease progression; two patients died due to their relapse. Median time for symptom resolution was 8 weeks. Outcomes did not vary by comparing CTLA-4 and PD-1/PD-L1 inhibitors.

Conclusions

Reported MS relapses after ICI are rare, but the adverse events described include rapid neurologic progression and death. Larger and prospective studies are warranted to assess disability and long-term outcomes and outweigh the risks of starting immunotherapy in patients with MS.
Literature
1.
go back to reference Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015;372:311–9.CrossRefPubMed Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015;372:311–9.CrossRefPubMed
2.
go back to reference Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627–39.CrossRefPubMedPubMedCentral Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627–39.CrossRefPubMedPubMedCentral
3.
go back to reference Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:123–35.CrossRefPubMedPubMedCentral Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:123–35.CrossRefPubMedPubMedCentral
4.
go back to reference Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372:2018–28.CrossRefPubMed Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372:2018–28.CrossRefPubMed
5.
go back to reference Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387:1540–50.CrossRefPubMed Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387:1540–50.CrossRefPubMed
6.
go back to reference Larkin J, Hodi FS, Wolchok JD. Combined Nivolumab and Ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:1270–1.CrossRefPubMed Larkin J, Hodi FS, Wolchok JD. Combined Nivolumab and Ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:1270–1.CrossRefPubMed
8.
go back to reference Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372:320–30.CrossRefPubMed Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372:320–30.CrossRefPubMed
9.
go back to reference Robert C, Schachter J, Long GV, et al. Pembrolizumab versus Ipilimumab in advanced melanoma. N Engl J Med. 2015;372:2521–32.CrossRefPubMed Robert C, Schachter J, Long GV, et al. Pembrolizumab versus Ipilimumab in advanced melanoma. N Engl J Med. 2015;372:2521–32.CrossRefPubMed
10.
go back to reference Gulley JL, Madan RA, Pachynski R et al. (2017) Role of antigen spread and distinctive characteristics of immunotherapy in cancer treatment. J Natl Cancer Institute 109 Gulley JL, Madan RA, Pachynski R et al. (2017) Role of antigen spread and distinctive characteristics of immunotherapy in cancer treatment. J Natl Cancer Institute 109
11.
go back to reference Khoury SJ, Sayegh MH. The roles of the new negative T cell costimulatory pathways in regulating autoimmunity. Immunity. 2004;20:529–38.CrossRefPubMed Khoury SJ, Sayegh MH. The roles of the new negative T cell costimulatory pathways in regulating autoimmunity. Immunity. 2004;20:529–38.CrossRefPubMed
12.
13.
14.
go back to reference Anonymous. Global, regional, and national burden of neurological disorders during 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. The Lancet. Neurology. 2017;16:877–97.CrossRef Anonymous. Global, regional, and national burden of neurological disorders during 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. The Lancet. Neurology. 2017;16:877–97.CrossRef
15.
16.
go back to reference Weiner HL. Multiple sclerosis is an inflammatory T-cell-mediated autoimmune disease. Arch Neurol. 2004;61:1613–5.CrossRefPubMed Weiner HL. Multiple sclerosis is an inflammatory T-cell-mediated autoimmune disease. Arch Neurol. 2004;61:1613–5.CrossRefPubMed
17.
go back to reference Ascherio A, Munger KL. Epidemiology of multiple sclerosis: from risk factors to prevention—an update. Semin Neurol. 2016;36:103–14.CrossRefPubMed Ascherio A, Munger KL. Epidemiology of multiple sclerosis: from risk factors to prevention—an update. Semin Neurol. 2016;36:103–14.CrossRefPubMed
18.
go back to reference Kwek SS, Dao V, Roy R et al. (2012) Diversity of antigen-specific responses induced in vivo with CTLA-4 blockade in prostate cancer patients. J Immunol 189:3759–3766 Kwek SS, Dao V, Roy R et al. (2012) Diversity of antigen-specific responses induced in vivo with CTLA-4 blockade in prostate cancer patients. J Immunol 189:3759–3766
19.
20.
go back to reference Numico G, Cristofano A, Mozzicafreddo A, et al. Hospital admission of cancer patients: avoidable practice or necessary care? PLoS ONE. 2015;10:e0120827.CrossRefPubMedPubMedCentral Numico G, Cristofano A, Mozzicafreddo A, et al. Hospital admission of cancer patients: avoidable practice or necessary care? PLoS ONE. 2015;10:e0120827.CrossRefPubMedPubMedCentral
21.
go back to reference Larkin J, Chmielowski B, Lao CD, et al. Neurologic serious adverse events associated with nivolumab plus ipilimumab or nivolumab alone in advanced melanoma, including a case series of encephalitis. Oncologist. 2017;22:709–18.CrossRefPubMedPubMedCentral Larkin J, Chmielowski B, Lao CD, et al. Neurologic serious adverse events associated with nivolumab plus ipilimumab or nivolumab alone in advanced melanoma, including a case series of encephalitis. Oncologist. 2017;22:709–18.CrossRefPubMedPubMedCentral
22.
go back to reference Spain L, Walls G, Julve M, et al. Neurotoxicity from immune-checkpoint inhibition in the treatment of melanoma: a single centre experience and review of the literature. Ann Oncol. 2017;28:377–85.PubMed Spain L, Walls G, Julve M, et al. Neurotoxicity from immune-checkpoint inhibition in the treatment of melanoma: a single centre experience and review of the literature. Ann Oncol. 2017;28:377–85.PubMed
23.
go back to reference Voskens CJ, Goldinger SM, Loquai C, et al. The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network. PLoS ONE. 2013;8:e53745.CrossRefPubMedPubMedCentral Voskens CJ, Goldinger SM, Loquai C, et al. The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network. PLoS ONE. 2013;8:e53745.CrossRefPubMedPubMedCentral
24.
go back to reference Zimmer L, Goldinger SM, Hofmann L et al. (2016) Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy. Eur J Cancer (Oxford, England 1990) 60:210–225 Zimmer L, Goldinger SM, Hofmann L et al. (2016) Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy. Eur J Cancer (Oxford, England 1990) 60:210–225
25.
go back to reference Fellner A, Makranz C, Lotem M et al. (2018) Neurologic complications of immune checkpoint inhibitors. J Neurooncol Fellner A, Makranz C, Lotem M et al. (2018) Neurologic complications of immune checkpoint inhibitors. J Neurooncol
26.
go back to reference Liao B, Shroff S, Kamiya-Matsuoka C, et al. Atypical neurological complications of ipilimumab therapy in patients with metastatic melanoma. Neuro-oncology. 2014;16:589–93.CrossRefPubMedPubMedCentral Liao B, Shroff S, Kamiya-Matsuoka C, et al. Atypical neurological complications of ipilimumab therapy in patients with metastatic melanoma. Neuro-oncology. 2014;16:589–93.CrossRefPubMedPubMedCentral
27.
go back to reference Noseworthy JH, Lucchinetti C, Rodriguez M, et al. Multiple sclerosis. N Engl J Med. 2000;343:938–52.CrossRefPubMed Noseworthy JH, Lucchinetti C, Rodriguez M, et al. Multiple sclerosis. N Engl J Med. 2000;343:938–52.CrossRefPubMed
28.
29.
30.
go back to reference Sarangdhar M, Tabar S, Schmidt C, et al. Data mining differential clinical outcomes associated with drug regimens using adverse event reporting data. Nat Biotechnol. 2016;34:697–700.CrossRefPubMed Sarangdhar M, Tabar S, Schmidt C, et al. Data mining differential clinical outcomes associated with drug regimens using adverse event reporting data. Nat Biotechnol. 2016;34:697–700.CrossRefPubMed
31.
go back to reference Harinstein L, Wu E, Brinker A. Postmarketing cases of eluxadoline-associated pancreatitis in patients with or without a gallbladder. Aliment Pharmacol Ther. 2018;47:809–15.CrossRefPubMed Harinstein L, Wu E, Brinker A. Postmarketing cases of eluxadoline-associated pancreatitis in patients with or without a gallbladder. Aliment Pharmacol Ther. 2018;47:809–15.CrossRefPubMed
32.
go back to reference Gettings EJ, Hackett CT, Scott TF. Severe relapse in a multiple sclerosis patient associated with ipilimumab treatment of melanoma. Multiple sclerosis (Houndmills, Basingstoke, England). 2015;21:670.CrossRef Gettings EJ, Hackett CT, Scott TF. Severe relapse in a multiple sclerosis patient associated with ipilimumab treatment of melanoma. Multiple sclerosis (Houndmills, Basingstoke, England). 2015;21:670.CrossRef
33.
go back to reference Gómez Vicente L, Rubio Viqueira B, Jimenez De Las Peñas M et al. (2016) P04.07 Relapse in a paucisymptomatic form of multiple sclerosis in a patient treated with nivolumab. Neuro-oncology 18:iv25–iv25 Gómez Vicente L, Rubio Viqueira B, Jimenez De Las Peñas M et al. (2016) P04.07 Relapse in a paucisymptomatic form of multiple sclerosis in a patient treated with nivolumab. Neuro-oncology 18:iv25–iv25
34.
go back to reference Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239–45.CrossRef Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239–45.CrossRef
35.
go back to reference Zehou O, Leibler C, Arnault JP et al. (2018) Ipilimumab for the treatment of advanced melanoma in six kidney transplant patients. Am J Transpl Zehou O, Leibler C, Arnault JP et al. (2018) Ipilimumab for the treatment of advanced melanoma in six kidney transplant patients. Am J Transpl
36.
go back to reference Cuzzubbo S, Javeri F, Tissier M et al. (2017) Neurological adverse events associated with immune checkpoint inhibitors: review of the literature. Eur J Cancer (Oxford, England 1990) 73:1–8 Cuzzubbo S, Javeri F, Tissier M et al. (2017) Neurological adverse events associated with immune checkpoint inhibitors: review of the literature. Eur J Cancer (Oxford, England 1990) 73:1–8
38.
go back to reference Zukas AM, Schiff D. Neurological complications of new chemotherapy agents. Neuro-oncology. 2018;20:24–36.CrossRefPubMed Zukas AM, Schiff D. Neurological complications of new chemotherapy agents. Neuro-oncology. 2018;20:24–36.CrossRefPubMed
37.
go back to reference Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378:158–68.CrossRefPubMed Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378:158–68.CrossRefPubMed
39.
go back to reference Kao JC, Liao B, Markovic SN, et al. Neurological complications associated with anti-programmed death 1 (PD-1) Antibodies. JAMA Neurol. 2017;74:1216–22.CrossRefPubMedPubMedCentral Kao JC, Liao B, Markovic SN, et al. Neurological complications associated with anti-programmed death 1 (PD-1) Antibodies. JAMA Neurol. 2017;74:1216–22.CrossRefPubMedPubMedCentral
40.
go back to reference Haanen J, Carbonnel F, Robert C et al. (2017) Management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 28:iv119–iv142 Haanen J, Carbonnel F, Robert C et al. (2017) Management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 28:iv119–iv142
41.
go back to reference Tobin WO, Pittock SJ (2017) autoimmune neurology of the central nervous system. Continuum (Minneapolis, Minn.) 23:627–653 Tobin WO, Pittock SJ (2017) autoimmune neurology of the central nervous system. Continuum (Minneapolis, Minn.) 23:627–653
42.
go back to reference Johnson DB, Sullivan RJ, Ott PA, et al. Ipilimumab therapy in patients with advanced melanoma and preexisting autoimmune disorders. JAMA Oncol. 2016;2:234–40.CrossRefPubMed Johnson DB, Sullivan RJ, Ott PA, et al. Ipilimumab therapy in patients with advanced melanoma and preexisting autoimmune disorders. JAMA Oncol. 2016;2:234–40.CrossRefPubMed
43.
go back to reference Menzies AM, Johnson DB, Ramanujam S, et al. Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Ann Oncol. 2017;28:368–76.CrossRefPubMed Menzies AM, Johnson DB, Ramanujam S, et al. Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Ann Oncol. 2017;28:368–76.CrossRefPubMed
44.
go back to reference Kuo JC, Lilly LB, Hogg D. Immune checkpoint inhibitor therapy in a liver transplant recipient with a rare subtype of melanoma: a case report and literature review. Melanoma Res. 2018;28:61–4.CrossRef Kuo JC, Lilly LB, Hogg D. Immune checkpoint inhibitor therapy in a liver transplant recipient with a rare subtype of melanoma: a case report and literature review. Melanoma Res. 2018;28:61–4.CrossRef
45.
go back to reference Kwatra V, Karanth NV, Priyadarshana K, et al. Pembrolizumab for metastatic melanoma in a renal allograft recipient with subsequent graft rejection and treatment response failure: a case report. J Med Case Rep. 2017;11:73.CrossRefPubMedPubMedCentral Kwatra V, Karanth NV, Priyadarshana K, et al. Pembrolizumab for metastatic melanoma in a renal allograft recipient with subsequent graft rejection and treatment response failure: a case report. J Med Case Rep. 2017;11:73.CrossRefPubMedPubMedCentral
46.
go back to reference Shoenfeld Y, Agmon-Levin N. 'ASIA'—autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun. 2011;36:4–8.CrossRefPubMed Shoenfeld Y, Agmon-Levin N. 'ASIA'—autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun. 2011;36:4–8.CrossRefPubMed
Metadata
Title
Multiple sclerosis outcomes after cancer immunotherapy
Authors
Catherine R. Garcia
Rani Jayswal
Val Adams
Lowell B. Anthony
John L. Villano
Publication date
01-10-2019
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology / Issue 10/2019
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-019-02060-8

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