Multiple sclerosis outcomes after cancer immunotherapy

García, Cézar; Jayswal, Rani; Adams, Val R.; Anthony, Lowell; Villanó, John L.

doi:10.1007/s12094-019-02060-8

Cited by 91 publications

(87 citation statements)

References 47 publications

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“…In most phase III studies investigating ICI based treatments patients with pre-existing autoimmune diseases have [12]. A recent meta-analysis found that flares of MS during ICI treatment are rare, but severe [13]. To date, in our case, neither pembrolizumab nor ipilimumb lead to RRMS flares, despite cessation of treatment with fingolimod, while effectively treating cancer.…”

Section: Discussionmentioning

confidence: 68%

Ocular Adverse Events Induced by Immune Checkpoint Inhibitors: A Comprehensive Pharmacovigilance Analysis

Bomze

Meirson

Ali

et al. 2020

Ocular Immunology and Inflammation

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PURPOSE Characterize ocular adverse events (oAEs) caused by immune checkpoint inhibitors (ICIs). METHODS Retrospective analysis of 41,674 cancer patients in the FDA Adverse Event Reporting System (FAERS) pharmacovigilance database receiving anti-PD-1/PD-L1, anti-CTLA-4, or anti-PD-1+ anti-CTLA-4 combination. Reporting odds ratio (ROR) was used to approximate oAE rate across regimens and indications. RESULTS The most common indications were lung cancer (27.3%) and melanoma (22.7%); 76.3% received anti-PD-1/PD-L1 monotherapy. 1,268 patients (3.0%) reported oAEs, namely vision disorders (30.8%), uveitis (15.1%), and retinal, lacrimal, and optic nerve disorders (10.7%, 9.0%, 8.4%). Melanoma showed the highest proportion of uveitis (117/9,471 cases; 1.2%). Addition of anti-CTLA-4 to anti-PD-1 increased the ROR of uveitis from 4.77 (95% CI 3.83-5.94) to 17.1 (95% CI 12.9-22.7). Among anti-PD-1/PD-L1 cases, uveitis was differentially reported in melanoma (ROR 14.7, 95% CI 10.7-20.2) compared with lung cancer (ROR 2.67, 95% CI 1.68-4.23). CONCLUSION ICI-induced oAEs are rare, and uveitis is significantly associated with melanoma and anti-PD-1+ anti-CTLA-4 combination.

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Section: Discussionmentioning

confidence: 68%

Ocular Adverse Events Induced by Immune Checkpoint Inhibitors: A Comprehensive Pharmacovigilance Analysis

Bomze

Meirson

Ali

et al. 2020

Ocular Immunology and Inflammation

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“…4,24 The most common irAEs of the CNS includes encephalitis, aseptic meningitis, and myelitis. Some irAEs of the CNS are extremely rare, such as multiple sclerosis (MS), 25 posterior reversible encephalopathy syndrome, 26 neurosarcoidosis, 27 cerebral vasculitis, 28 Tolosa-Hunt syndrome, 29 and Vogt-Koyanagi-Harada syndrome. 30 Given the high fatality rate of irAEs of the CNS (encephalitis, 6.3-12.8%; meningitis, 7.4-8.3% 19,20 ), patients should be recognized promptly and treated with immune-modulating agents without delay.…”

Section: Neurological Iraes Affecting the Cnsmentioning

confidence: 99%

Neurological immune‐related adverse events associated with immune checkpoint inhibitors: A review of the literature

Fan

Ren

Zhao

et al. 2020

Asia-Pac J Clncl Oncology

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Immune checkpoint inhibitors (ICIs) have made a breakthrough in cancer therapy. Patients treated with ICIs may develop immune-related adverse events (irAEs) due to the upregulated activity of the immune system. With the increasing use of ICIs, irAEs are more frequently reported and have become important challenges in many patients. Neurological irAEs, which include encephalitis, myelitis, aseptic meningitis, peripheral neuropathy, myasthenia gravis, and myositis, consist of a distinct group of neuroinflammatory disorders. These disorders are rare but frequently severe with high mortality and morbidity. Patients with neurological irAEs are generally responsive to immune-modulating therapy. Therefore, early recognition and treatment are the most important ways to improve their prognosis. Here, we provide a comprehensive review of neurological irAEs associated with ICIs and focus on these affecting central nervous systems.

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“…Another case, described by Gettings et al, was of a 56-year-old male with MS with recurrent melanoma after multiple resections; he was treated with ipilimumab who developed two MS flare-ups, leaving him with disability from MS relapse but had remission of melanoma on PET scan 14 . Garcia et al conducted a retrospective analysis capturing 42,529 adverse events with the use of ICI with 13 cases identified with MS. Of the 13, eight had a previous diagnosis of MS. All the patients in their analysis experienced progression of their MS, and two patients died following their MS relapse 15 .…”

Section: Discussionmentioning

confidence: 99%

Case Report: A case of immune checkpoint inhibitor therapy in a patient with multiple sclerosis

et al. 2020

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Immune checkpoint inhibitors (ICIs) have rapidly shifted the landscape of treatments in malignancy with significant improvements in survival paradigm. They have been an attractive armamentarium to the oncologists given the limited immune adverse effects with potential for deeper and durable benefits that haven't been previously noticed with chemotherapy. However, they result in unique toxicities by limiting immune self-tolerance and cause immune-mediated endocrinopathies, such as hypothyroidism, pneumonitis, colitis, hepatitis, myocarditis, meningitis, hypophysitis, etc. As such, they are contraindicated in patients with autoimmune disorders or recipients of organ transplants given the risk for reactivation or flare of the underlying autoimmune disease and rejection of the donor organ in transplants, although sporadic cases have been reported with the use of immunotherapy in such patients. Malignant melanoma is a highly aggressive cancer, with only 15-20% five-year survival rate once it has spread to the lymph nodes or has distant metastasis. ICIs have changed the landscape of advanced melanoma with exponential improvements in survival, the 5-year survival rates are about 50%. Multiple sclerosis (MS) is recognized as T cell-mediated immune response causing inflammation, which causes local inflammatory plaques and demyelination. ICIs are likely to generate an immune response that causes molecular mimicry and cross-react with CNS autoantigens, in turn exacerbating pre-existing immune response and subsequent flare-ups in MS. There is little knowledge about treating such patients with immunotherapy, short of a few case reports and series; in this report, we describe another such case. We present a case of checkpoint inhibitor therapy in a patient with multiple sclerosis who underwent immune checkpoint inhibitor therapy with pembrolizumab for metastatic malignant melanoma who had a complete response to treatment at the cost of MS relapse, which was managed with high-dose steroids.

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Multiple sclerosis outcomes after cancer immunotherapy

Cited by 91 publications

References 47 publications

Ocular Adverse Events Induced by Immune Checkpoint Inhibitors: A Comprehensive Pharmacovigilance Analysis

Ocular Adverse Events Induced by Immune Checkpoint Inhibitors: A Comprehensive Pharmacovigilance Analysis

Neurological immune‐related adverse events associated with immune checkpoint inhibitors: A review of the literature

Case Report: A case of immune checkpoint inhibitor therapy in a patient with multiple sclerosis

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