Advertisement

Immune checkpoint inhibition in patients with inactive pre-existing neuromuscular autoimmune diseases

      Abstract

      Objectives

      To evaluate the safety of immune checkpoint inhibitor use in patients with pre-existing neurological autoimmune diseases.

      Methods

      In this retrospective case-series, we examined exacerbations of underlying disease and the occurrence of immune-related adverse events in 5 patients who had been diagnosed with a neurological autoimmune disease prior to receiving immune checkpoint inhibitor therapy for advanced malignancy.

      Results

      Two patients had a prior diagnosis of myasthenia gravis, two had Guillain-Barré syndrome, and one had chronic idiopathic demyelinating polyneuropathy. Only one patient experienced a flare of neurological autoimmune disease. Four of the five patients experienced immune-related adverse events unrelated to their neurological disease.

      Conclusions

      In this case-series, exacerbations of neurological autoimmune disease were less common and less severe than expected. Further research is needed to determine which individuals are at greatest risk of neurological autoimmune disease complication while receiving immune checkpoint inhibitor therapy.

      Keywords

      Abbreviations:

      ICI (Immune checkpoint inhibitor), irAE (immune-related adverse event), AID (autoimmune disease), MG (myasthenia gravis), GBS (Guillian-Barré syndrome), nAID (neurological autoimmune disease), CIDP (chronic inflammatory demyelinating polyneuropathy), CTCAE (Common Terminology Criteria for Adverse Events), SBRT (stereotactic body radiation therapy), IVIG (intravenous immunoglobulin)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of the Neurological Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Haslam A.
        • Gill J.
        • Prasad V.
        Estimation of the percentage of US patients with Cancer who are eligible for immune checkpoint inhibitor drugs.
        JAMA Netw. Open. 2020; 3
        • Kruger S.
        • et al.
        Advances in cancer immunotherapy 2019 – latest trends.
        J. Exp. Clin. Cancer Res. 2019; 38: 1-11
        • Kennedy L.B.
        • Salama A.K.S.
        A review of cancer immunotherapy toxicity.
        CA Cancer J. Clin. 2020; 70: 86-104
        • Khan S.
        • Gerber D.E.
        Autoimmunity, checkpoint inhibitor therapy and immune-related adverse events: a review.
        Semin. Cancer Biol. 2020; 64: 93-101
        • Brahmer J.R.
        • et al.
        Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.
        N. Engl. J. Med. 2012; 366: 2455-2465
        • Topalian S.L.
        • et al.
        Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
        N. Engl. J. Med. 2012; 366: 2443-2454
        • Hodi F.S.
        • et al.
        Improved survival with ipilimumab in patients with metastatic melanoma.
        N. Engl. J. Med. 2010; 363: 711-723
        • Hamid O.
        • et al.
        Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma.
        N. Engl. J. Med. 2013; 369: 134-144
        • Dubey A.D.
        • et al.
        Severe neurological toxicity of immune checkpoint inhibitors.
        Ann. Neurol. 2020; 87: 659-669
        • Johnson D.B.
        • et al.
        Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study.
        J. Immunother. Cancer. 2020; 7: 1-9
        • Kao J.C.
        • et al.
        Neurological complications associated with anti–programmed death 1 (PD-1) antibodies.
        JAMA Neurol. 2017; 74: 1216-1222
        • Sato K.
        • et al.
        Neurological and related adverse events in immune checkpoint inhibitors: a pharmacovigilance study from the Japanese adverse drug event report database.
        J. Neuro-Oncol. 2019; 145: 1-9
        • Efuni E.
        • et al.
        Risk of toxicity after initiating immune checkpoint inhibitor treatment in patients with rheumatoid arthritis.
        J. Clin. Rheumatol. 2021; 27: 267-271
        • Coureau M.
        • et al.
        Efficacy and toxicity of immune -checkpoint inhibitors in patients with preexisting autoimmune disorders.
        Front. Med. 2020; 7: 137-143
        • Martins F.
        • et al.
        Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance.
        Nat. Rev. Clin. Oncol. 2019; 16: 563-580
        • Haanen J.
        • et al.
        Management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up.
        Ann. Oncol. 2017; 28 (p. iv119-iv142)
        • Michot J.M.
        • et al.
        Immune-related adverse events with immune checkpoint blockade: a comprehensive review.
        Eur. J. Cancer. 2016; 54: 139-148
        • Richter M.D.
        • et al.
        Immunologic adverse events from immune checkpoint therapy.
        Best Pract. Res. Clin. Rheumatol. 2020; 101511
        • Earl D.E.
        • Loochtan A.I.
        • Bedlack R.S.
        Refractory myasthenia gravis exacerbation triggered by pembrolizumab.
        Muscle Nerve. 2018; 57: E120-E121
        • Cooper D.S.
        • et al.
        Severe exacerbation of myasthenia gravis associated with checkpoint inhibitor immunotherapy.
        J. Neuromuscul. Dis. 2017; 4: 169-173
        • Lau K.H.
        • et al.
        Exacerbation of myasthenia gravis in a patient with melanoma treated with pembrolizumab.
        Muscle Nerve. 2016; 54: 157-161
        • Maeda O.
        • et al.
        Nivolumab for the treatment of malignant melanoma in a patient with pre-existing myasthenia gravis.
        Nagoya J. Med. Sci. 2016; 78: 119-122
        • Mitsune A.
        • et al.
        Relapsed myasthenia gravis after Nivolumab treatment.
        Intern. Med. 2018; 57: 1893-1897
        • Phadke S.D.
        • et al.
        Pembrolizumab therapy triggering an exacerbation of preexisting autoimmune disease: a report of 2 patient cases.
        J. Investig. Med. High Impact Case Rep. 2016; 4 (p. ePub)
        • Yuen C.
        • et al.
        Severe relapse of vaccine-induced Guillain-Barré syndrome after treatment with Nivolumab.
        J. Clin. Neuromuscul. Dis. 2019; 20: 194-199
        • Shimamoto S.
        • Allen A.
        • Rakocevic G.
        Worsening chronic inflammatory demyelinating polyneuropathy after Pembrolizumab treatment of metastatic melanoma: a case report (P1.458).
        Neurology. 2018; 90 (p. P1.458)
        • Gettings E.J.
        • Hackett C.T.
        • Scott T.F.
        Severe relapse in a multiple sclerosis patient associated with ipilimumab treatment of melanoma.
        Mult. Scler. 2015; 21: 670
        • Menzies A.M.
        • et al.
        Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab.
        Ann. Oncol. 2016; 28: 368-376
        • Leonardi G.C.
        • et al.
        Safety of programmed Death-1 pathway inhibitors among patients with non-small-cell lung Cancer and preexisting autoimmune disorders.
        J. Clin. Oncol. 2018; 36: 1905-1912
        • Kähler K.C.
        • et al.
        Ipilimumab in metastatic melanoma patients with pre-existing autoimmune disorders.
        Cancer Immunol. Immunother. 2018; 67: 825-834
        • Johnson D.B.
        • et al.
        Ipilimumab therapy in patients with advanced melanoma and preexisting autoimmune disorders.
        JAMA Oncol. 2016; 2: 234-240
        • Cortellini A.
        • et al.
        Safe Administration of Ipilimumab, Pembrolizumab, and Nivolumab in a patient with metastatic melanoma, psoriasis, and a previous Guillain-Barré syndrome.
        Case Rep. Oncol. Med. 2018; 2018: 1-4
        • Wang C.
        • Sandhu J.
        • Fakih M.
        Complete response to pembrolizumab in a patient with metastatic colon cancer with microsatellite instability and a history of Guillain-Barre syndrome.
        J. Gastrointest. Oncol. 2019; 10: 161-165
        • Sechi E.
        • et al.
        Neurologic autoimmunity and immune checkpoint inhibitors: autoantibody profiles and outcomes.
        Neurology. 2020; 95: e2442-e2452