Neurologic outcomes in people with multiple sclerosis treated with immune checkpoint inhibitors for oncologic indications

Neurologic outcomes in people with multiple sclerosis treated with immune checkpoint inhibitors for oncologic indications | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Neurologic outcomes in people with multiple sclerosis treated with immune checkpoint inhibitors for oncologic indications Carson M. Quinn , Prashanth Rajarajan , Alexander Gill , Hannah Kopinsky , Andrew B. Wolf , Celeste Soares De Camargo , Jessica Lamb , Tamar Bacon , Joseph Murray , John C. Probasco , Kristin Galetta , Daniel Kantor , Patricia K. Coyle , Vikram Bhise , Enrique Alvarez , Sarah Conway , Shamik Bhattacharyya , Ilya Kister doi: https://doi.org/10.1101/2024.06.13.24308608 Carson M. Quinn 1 Department of Neurology, Brigham and Women’s Hospital Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: ilya.kister{at}nyulangone.org carsonquinnmd{at}gmail.com Prashanth Rajarajan 1 Department of Neurology, Brigham and Women’s Hospital Find this author on Google Scholar Find this author on PubMed Search for this author on this site Alexander Gill 2 Department of Neurology, Johns Hopkins University School of Medicine Find this author on Google Scholar Find this author on PubMed Search for this author on this site Hannah Kopinsky 3 Department of Neurology, NYU Grossman School of Medicine Find this author on Google Scholar Find this author on PubMed Search for this author on this site Andrew B. Wolf 4 Department of Neurology, University of Colorado School of Medicine Find this author on Google Scholar Find this author on PubMed Search for this author on this site Celeste Soares De Camargo 5 Department of Neurology, Rutgers – Robert Wood Johnson Medical School Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jessica Lamb 10 Department of Neurology, Stony Brook University Medical Center Find this author on Google Scholar Find this author on PubMed Search for this author on this site Tamar Bacon 3 Department of Neurology, NYU Grossman School of Medicine Find this author on Google Scholar Find this author on PubMed Search for this author on this site Joseph Murray 6 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine Find this author on Google Scholar Find this author on PubMed Search for this author on this site John C. Probasco 2 Department of Neurology, Johns Hopkins University School of Medicine Find this author on Google Scholar Find this author on PubMed Search for this author on this site Kristin Galetta 8 Department of Neurology, Stanford University Find this author on Google Scholar Find this author on PubMed Search for this author on this site Daniel Kantor 9 Medical Partnership 4 MS+ (MP4MS+) Find this author on Google Scholar Find this author on PubMed Search for this author on this site Patricia K. Coyle 10 Department of Neurology, Stony Brook University Medical Center Find this author on Google Scholar Find this author on PubMed Search for this author on this site Vikram Bhise 5 Department of Neurology, Rutgers – Robert Wood Johnson Medical School Find this author on Google Scholar Find this author on PubMed Search for this author on this site Enrique Alvarez 4 Department of Neurology, University of Colorado School of Medicine Find this author on Google Scholar Find this author on PubMed Search for this author on this site Sarah Conway 1 Department of Neurology, Brigham and Women’s Hospital Find this author on Google Scholar Find this author on PubMed Search for this author on this site Shamik Bhattacharyya 1 Department of Neurology, Brigham and Women’s Hospital Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ilya Kister 3 Department of Neurology, NYU Grossman School of Medicine Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: ilya.kister{at}nyulangone.org carsonquinnmd{at}gmail.com Abstract Full Text Info/History Metrics Supplementary material Data/Code Preview PDF Abstract Objective To assess the prevalence of multiple sclerosis (MS) activity, as well as neurologic and non-neurologic immune-related adverse events (irAEs) in persons with MS (pwMS) treated with immune checkpoint inhibitors (ICIs) for cancer. Background ICIs are associated with irAEs and exacerbation of certain preexisting autoimmune diseases. PwMS are generally excluded from ICI clinical trials, so data on the safety of these drugs in pwMS is limited. Design/Methods Participating sites were recruited through the Medical Partnership 4 MS+ (MP4MS+) listserv. Seven large academic centers participated in the study, each conducting a systematic search of their electronic medical record system for patients with MS and ICI exposure. Demographics and data on MS and cancer history, treatments, and outcomes were abstracted from patient charts using a structured instrument. Results We identified 66 pwMS (median age 66 years, 73% female, 68% not on disease-modifying therapy (DMT) for MS) who were treated with ICIs for lung cancers (35%), melanoma (21%) or other oncologic indications. During post-ICI follow-up (median: 11.7 months, range 0.2-106.3 months), two pwMS (3%) had relapse or MRI activity, three (5%) had neurologic irAEs, and 21 (32%) had non-neurologic irAEs. At the last follow-up, 25 (38%) subjects had partial or complete remission of their cancer while 35 (53%) were deceased. Conclusions In this multi-institutional systematic retrospective study of predominantly older pwMS who were off DMTs, MS activity and neurologic irAEs following ICI treatment were rare, suggesting that preexisting MS should not preclude the use of ICIs. Introduction Immune checkpoint inhibitors (ICIs) are increasingly used for a variety of cancers [ 1 ]. ICIs enhance the host anti-tumor immune response by blocking “immune checkpoints” – T-cell expressed programmed cell death protein 1 (PD-1), PD-1 ligand (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4). A well-recognized side effect of immune upregulation is the development of immune-related adverse events (irAEs). It is estimated that 5% of irAEs involve the nervous system – neurologic irAEs, or nirAEs [ 2 , 3 ] – manifesting as meningitis, encephalitis, myasthenia gravis (MG), myositis, Guillain–Barre Syndrome (GBS), and chronic peripheral neuropathies. Patients with systemic preexisting autoimmune diseases have increased rates of irAEs and may experience worsening of their autoimmune disease [ 4 ]. Because typical MS syndromes, such as optic neuritis, transverse myelitis, and tumefactive demyelinating lesions, have been reported as nirAEs in patients on ICI, there is concern that the risk of these events would be increased in patients with preexisting MS [ 3 , 5 ]. For this reason, pwMS were excluded from the major ICI trials and the safety profile of ICI use in pwMS is not well-characterized [ 6 ]. Initial case reports of pwMS receiving ICIs raised concerns about the risk of disease activity. Of the first 10 published cases of pwMS receiving ICIs for cancer treatment, 60% reported MS relapses after an average of 13.6 weeks, with symptoms of weakness, ataxia, optic neuritis, and brainstem syndromes [ 7 ]. However, only 2 of these 6 patients had poor neurologic outcomes, and in these 2 patients with poor outcomes, it was unclear if neurologic worsening was due to MS or other factors such as CNS radiation or nirAEs. Moreover, it is well recognized that case reports are biased toward worse outcomes, leading to overestimates of the risk of adverse events [ 6 ]. More recently, a few retrospective case series that assess the risk of relapse in MS following ICI have been published. In a multicenter case series from France, 18 pwMS who received ICIs were identified by treating clinicians. Clinical or radiographic worsening of MS was recorded in 3 patients (17%) within 6 months of ICI initiation. The authors noted that relapses occurred in younger patients who had stopped high-efficacy anti-trafficking DMTs, which are associated with disease rebound on discontinuation [ 8 ] and, therefore, may not be related to ICI. In a single-center study of 7 pwMS, no clinical relapses were reported following ICI start, but there were 2 cases of asymptomatic MRI lesions [ 9 ]. A case series from Brigham #x0026; Women’s Hospital also reported a very low rate of MS events [ 10 ]; the patients from this series were included in the current study. Reassuringly, although with limited data, pwMS also did not appear to have increased rates of irAEs, in contrast to what has been reported for other systemic autoimmune diseases [ 7 , 11 ]. The aim of this study was to assess the rate of MS activity as well as of neurologic and non-neurologic irAEs in all ICI-treated pwMS from seven large academic centers across the United States. Methods Participating sites were identified through the Medical Partnership 4 Multiple Sclerosis+ (MP4MS+) network, a platform for advocacy, clinical, and non-industry-funded research collaborations comprised of over 1,300 neurologists who treat pwMS. Investigators from the following institutions obtained IRB approval from their respective institutions and participated in the study: Mass General Brigham (Boston, MA), University of Colorado School of Medicine (Aurora, CO), Johns Hopkins Medicine (Baltimore, MD), Stanford University Medical Center (Palo Alto, CA), New York University Grossman School of Medicine (New York, NY), Stony Brook Medical Center (Stony Brook, NY), and Robert Wood Johnson Medical – Rutgers (Newark, NJ). Investigators at each site identified patients through institution-wide searches of the respective electronic medical record (EMR) system for patients with diagnosis codes of MS and treatment with any FDA-approved ICI (pembrolizumab, nivolumab, atezolizumab, cemiplimab, duravalamab, avelumab). We included all patients with a preexisting diagnosis of MS (confirmed by a neuroimmunologist at each site) who received at least one dose of an FDA-approved ICI medication for the treatment of cancer. Patients with Neuromyelitis Optica Spectrum Disease (NMOSD), Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD), Radiographically Isolated Syndrome, Clinically Isolated Syndrome, and those who developed MS after ICI start were excluded. Demographic and relevant clinical, laboratory, and radiologic data were extracted for each patient from the EMR using a comprehensive, structured instrument (Appendix 1). The key outcomes assessed were MS disease activity, nirAEs, non-neurologic irAEs following ICI initiation, and cancer outcomes. “MS disease activity” was defined as clinical relapse or new MRI lesions that could not be better attributed to CNS metastases or an alternative nirAE. MS activity was considered “related to ICI treatment” if it occurred within one year of the last ICI dose. Results We identified 66 patients (73% female) with preexisting MS diagnosis who received at least one dose of ICI. The number of patients contributed by each site is shown in Figure 1 . The median age at ICI initiation was 66.2 years (range 28.7-80.0 years). Most patients had inactive MS: 80.4% had no MS activity for ≥5 years, and 68.2% were off DMT at the time of ICI start. Details on the demographic and disease-related characteristics are shown in Table 1 , and patients’ treatment histories are summarized in Table 2 . Most patients received a single ICI, but 23% were on combination therapy. Importantly, 77% of patients were on cytotoxic chemotherapy at the time of ICI, and 21% had received cerebral radiation. The median duration of ICI treatment was 6.4 months (range: 1-39 months), with 17% of patients receiving only one cycle of ICI. The median post-ICI follow-up was 11.7 months. As expected, the follow-up was much shorter for deceased patients (n=35, median follow-up: 4 months) compared to those who were alive at the last follow-up (n=31, median follow-up: 24 months). The follow-up for each patient is shown in Figure 2 . View this table: View inline View popup Table 1. Baseline Characteristics View this table: View inline View popup Download powerpoint Table 2. Cohort Cancer Treatment and Oncologic Outcomes View this table: View inline View popup Download powerpoint Table 3. Outcomes – adverse events Download figure Open in new tab Figure 1. Map of sites in the MP4MS+ network which contributed patients to the cohort Download figure Open in new tab Figure 2. ICI-treatment duration and follow-up. A swimmer plot depicting ICI-treatment duration (blue) and subsequent follow-up time (orange) in years for each patient. Patients that were deceased at the time of last follow-up are marked with an asterisk (*). In total, of the 31 patients alive at last follow up, there was a median follow up of 2.11 years; and of the 35 deceased at last follow up, there was a median follow up duration of 0.34 years. MS disease activity within 1 year of ICI start was recorded for only 2 patients (3%). One male patient aged 60-65 years, without MS activity for greater than five years at the time of ICI start experienced a mild clinical relapse with enhancing MRI lesions and worsening gait that resolved with corticosteroids. The second patient (female, aged 60-65 years), without MS activity for greater than five years, who had two small asymptomatic T2 hyperintense lesions on the MRI brain 4 months after ICI start. Both were on DMT at the time of the new activity. One additional patient had radiographic MS disease activity, which was deemed unrelated to ICI as it occurred 15 months after cessation of ICI therapy. Detailed timelines for the three cases with MS activity are shown in Figure 3a . Download figure Open in new tab Figure 3. MS disease activity and neurologic irAEs clinical timeline. Timeline in years of patients with (A) MS disease activity and (B) neurologic irAEs within one year ICI-treatment. Of note, a third patient with MS disease activity post-ICI treatment is depicted, although this activity was more than one year after cessation of ICI-therapy. As younger patients tend to be at higher risk of MS relapses, we conducted a sub-analysis of patients in our series who were 50 years or younger at the time of ICI start. We identified 6 such patients, but, despite younger age, they also tended to have inactive MS, with a median of 5.3 years (range 2.3-8.3 years) between the last MS activity and ICI start. None of the 6 patients was on DMT at ICI start, though 3 had only recently discontinued treatment with interferon beta-1a, rituximab, and ocrelizumab. None of the 6 experienced MS activity or nirAEs during follow-up. Three patients had nirAEs one had encephalitis with seizures, one had a fatal case of Guillain-Barré Syndrome (despite treatment with high-dose intravenous corticosteroids and immunoglobulin [IVIG]), and one developed sensory neuronopathy. The timelines for these three patients are shown in Figure 3b . Non-neurologic irAEs were reported for 21 patients (32%) and were most commonly colitis, pneumonitis, and hepatitis ( Figure 4 ). Download figure Open in new tab Figure 4. Immune-related adverse events (irAEs) in people with MS. Schematic depicting all observed neurologic (orange) and non-neurologic (blue) irAEs observed in this cohort of people with MS exposed to ICI-therapy. Numbers beneath irAE type depict the number (percentage) of patients with each ICI-associated condition. As of the last follow-up, 38% of patients had complete or partial cancer remission, 53% were deceased, and the remainder either did not achieve remission or were missing data. Of the patients who were alive at the last follow-up, 48% were ambulatory without assistance. Discussion In our multicenter case series of 66 pwMS receiving ICIs for cancer, MS activity was observed in 3% of patients. This rate is similar to what would be expected in inactive MS patients of similar age who are not on ICI therapy [ 12 ]. We did not observe any patient with “disease rebound” (disease activity out of proportion to what has been observed prior to ICI). On the contrary, both MS events in our series were mild – one patient had asymptomatic MRI lesions, and the other had gait impairment responsive to corticosteroid treatment. In a recently published series from France, MS activity rate was numerically higher – in 3 out of 18 patients (17%) – than in our series; however, their patients were younger (median 48 vs 66 years in our series) and MS activity in two of the three patients in the French series occurred in the setting of discontinuation of natalizumab, a high-efficacy MS DMT associated with MS rebound [ 7 , 8 , 13 ]. Thus, post-ICI relapses in the French series could be related to stopping anti-trafficking DMT rather than to ICI. In our series, only 2 patients stopped anti-trafficking agents (fingolimod and natalizumab), but neither experienced any MS activity. A smaller, single-center series from UCSF reported no relapses in 7 patients [ 9 ]. Taken together, the three case series that examined MS activity after ICI therapy, including ours, comprise a total of 91 pwMS, of whom 2 (2.2%) had clinical relapses, and 5 (5.5%) had asymptomatic MRI activity [ 8 , 9 ]. Importantly, we examined not only MS activity in our patients but also rates of neurologic and non-neurologic irAEs. We found that the rate of nirAEs (5%) was similar to non-MS patients receiving ICI in the clinical trials, consistent with prior series [ 3 ]. The rate of non-neurologic irAE was 31.8% in our patients, which is within the range of what is expected in non-MS patients treated with ICIs [ 4 ]. Cancer remission was achieved in a minority of our patients (38%), while the majority were deceased at the last follow-up (53%), reflective of the advanced stage of their malignancies at the time of ICI initiation. Whether preexisting MS had delayed time to ICI initiation and whether earlier ICI use could have improved outcomes cannot be determined with our data but warrants further investigation. Why some autoimmune diseases predispose patients to higher-than-expected rates of preexisting disease exacerbation while MS does not is unknown [ 4 ]. Perhaps a higher degree of immune dysregulation in systemic autoimmune disorders compared to MS predisposes the former to ICI-related immune complications as well as to other immune diseases [ 14 ]. However, this is unlikely to be the only reason, as patients with other purely neurologic autoimmune diseases, such as MG, appear to be at high risk for ICI-related relapse [ 15 ]. At present, despite considerable efforts to identify biomarkers that would predict irAEs in patients who receive ICI, no biomarker has been validated for clinical use [ 16 ]. Further work to better understand the immunopathogenesis of irAEs may shed light on why certain conditions show a greater predisposition to this complication and lead to the development of reliable biomarkers of treatment-emergent autoimmunity that would make ICIs safer. Our study has several strengths. The model of using the broad network of MP4MS+ allowed us to identify multiple participating academic institutions across the US, resulting in the largest series of MS patients exposed to ICI – more than doubling the total number of cases of ICI in pwMS published to date. All investigators conducted comprehensive EMR searches that included all eligible patients from their institution, which reduces the risk of bias, whereby the more severe outcomes are more likely to be recalled and reported. Our median post-ICI follow-up was approximately a year, and 51 (78%) of patients had follow-up for 3 months, which is the period when most irAEs are reported. Our study shares the well-known limitations of retrospective design, including missing data, loss to follow-up, and lack of controls [ 17 ]. Patients receiving ICI typically have advanced cancer and high morbidity despite aggressive therapy. Thus, patients may not be able to follow up with their treating neurologist and receive a neurologic examination. Lacking such data, we are not able to comment on whether ICI has an impact on disease progression independent of relapse activity (PIRA). This question will need to be addressed in future studies, ideally with prospective follow-up. It is also important to note that not all patients had brain MRIs after ICI initiation – 39% had missing MRI data – and it is possible that asymptomatic lesions may have been missed. However, minor asymptomatic MRI changes do not typically have long-term implications for disability [ 18 ]. Lastly, because a minority of patients were deceased within 3 months of onset, which is the window for the emergence of most of the treatment-related irAEs, it is not possible to know what their MS course would have been like had they lived longer. It is important to emphasize that our patients were older relative to the typical MS clinic population, mostly had inactive MS for many years, and were off DMTs. Our conclusions about the lack of MS activity post-ICI may not be generalizable to younger pwMS with more active MS or those who stop anti-trafficking DMT (anti-integrin monoclonal antibodies, S1P receptor modulators) that are associated with disease rebound on discontinuation. Larger multicenter cohorts, inclusive of younger MS patients with more active disease, are needed to confirm and extend our findings. Moreover, most patients in our cohort were on prior or concomitant cytotoxic chemotherapy, which may reduce the risk of relapse and potentially offset the tendency to ICI-associated relapses. We are not able to comment on whether ICI would be similarly safe – from an MS standpoint – in pwMS who start ICI prior to receiving cytotoxic chemotherapy. Lastly, it should be emphasized that conclusions about the apparent safety of ICI in MS cannot be extrapolated to other neuroinflammatory conditions with different pathogenesis, such as NMOSD or MOGAD. Efforts are currently underway to explore the safety of ICI in these rare neuroinflammatory disorders, with preliminary evidence pointing to a different risk profile with ICI [ 19 ]. Despite the caveats, our data is reassuring in that older patients with inactive MS could receive ICI treatment for cancer without the risk of MS reactivation. Our findings argue that older pwMS should not be excluded from future clinical trials of ICIs. In younger patients, who may be at higher risk for relapses, it may be prudent to continue highly effective MS therapy while on ICI if this does not interfere with oncologic treatment. Special care is necessary to weigh the pros and cons of stopping anti-trafficking therapy prior to ICI, which may lead to disease rebound (independent of ICI treatment). Ideally, pwMS who initiate ICI should be under the care of a multidisciplinary team that includes a neurologist experienced with MS. Data Availability Deidentified data produced in the present study are available upon reasonable request to the authors Footnotes Disclosures: Dr Kantor reported personal fees from Viatris and an institutional research grant from Bristol Myers Squibb outside the submitted work. Dr. Kantor is the Co-Medical Director of the CorEvitas MS registry, in partnership with the National MS Society and the Founding President of the Medical Partnership 4 MS+ (MP4MS+). All other authors report no relevant disclosures. REFERENCES 1. ↵ Shiravand , Y. , et al. , Immune Checkpoint Inhibitors in Cancer Therapy . Curr Oncol , 2022 . 29 ( 5 ): p. 3044 – 3060 . OpenUrl CrossRef 2. ↵ Postow , M.A. , R. Sidlow , and M.D. Hellmann , Immune-Related Adverse Events Associated with Immune Checkpoint Blockade . N Engl J Med , 2018 . 378 ( 2 ): p. 158 – 168 . OpenUrl CrossRef PubMed 3. ↵ Dalakas , M.C. , Neurological complications of immune checkpoint inhibitors: what happens when you ‘take the brakes off’ the immune system . Ther Adv Neurol Disord , 2018 . 11 : p. 1756286418799864 . OpenUrl PubMed 4. ↵ Abdel-Wahab , N. , et al. , Use of Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Autoimmune Disease: A Systematic Review . Ann Intern Med , 2018 . 168 ( 2 ): p. 121 – 130 . OpenUrl CrossRef PubMed 5. ↵ Duong , S.L. , et al. , Neurotoxicities associated with immune checkpoint inhibitor therapy . J Neurooncol , 2021 . 152 ( 2 ): p. 265 – 277 . OpenUrl CrossRef PubMed 6. ↵ Tang , H. , J. Zhou , and C. Bai , The Efficacy and Safety of Immune Checkpoint Inhibitors in Patients With Cancer and Preexisting Autoimmune Disease . Front Oncol , 2021 . 11 : p. 625872 . OpenUrl 7. ↵ Aoun , R. , et al. , Immune Checkpoint Inhibitors in Patients with Pre-existing Neurologic Autoimmune Disorders . Curr Neurol Neurosci Rep , 2023 . 23 ( 11 ): p. 735 – 750 . OpenUrl 8. ↵ Androdias , G. , et al. , Impact of Immune Checkpoint Inhibitors on the Course of Multiple Sclerosis . Neurol Neuroimmunol Neuroinflamm , 2024 . 11 ( 2 ): p. e200202 . OpenUrl 9. ↵ Nylander , A.N. , et al. , Clinical outcomes after use of checkpoint inhibitor immunotherapies in people with multiple sclerosis . Mult Scler J Exp Transl Clin , 2024 . 10 ( 2 ): p. 20552173241252563 . OpenUrl 10. ↵ Conway , S.E. , et al. , Neurologic disease activity in people with multiple sclerosis treated with immune checkpoint inhibitors . Mult Scler , 2023 . 29 ( 3 ): p. 471 – 474 . OpenUrl 11. ↵ Danlos , F.X. , et al. , Safety and efficacy of anti-programmed death 1 antibodies in patients with cancer and pre-existing autoimmune or inflammatory disease . Eur J Cancer , 2018 . 91 : p. 21 – 29 . OpenUrl CrossRef PubMed 12. ↵ Corboy , J.R. , et al. , Risk of new disease activity in patients with multiple sclerosis who continue or discontinue disease-modifying therapies (DISCOMS): a multicentre, randomised, single-blind, phase 4, non-inferiority trial . Lancet Neurol , 2023 . 22 ( 7 ): p. 568 – 577 . OpenUrl CrossRef 13. ↵ Roos , I. , et al. , Disease Reactivation After Cessation of Disease-Modifying Therapy in Patients With Relapsing-Remitting Multiple Sclerosis . Neurology , 2022 . 99 ( 17 ): p. e1926 – e1944 . OpenUrl 14. ↵ Cojocaru , M. , I.M. Cojocaru , and I. Silosi , Multiple autoimmune syndrome . Maedica (Bucur) , 2010 . 5 ( 2 ): p. 132 – 4 . OpenUrl 15. ↵ Snavely , A. , et al. , Immune checkpoint inhibition in patients with inactive pre-existing neuromuscular autoimmune diseases . Journal of the Neurological Sciences , 2022 . 438 : p. 120275 . OpenUrl 16. ↵ Taylor , J. , et al. , Checkpoint inhibitor immune-related adverse events: A focused review on autoantibodies and B cells as biomarkers, advancements and future possibilities . Front Immunol , 2022 . 13 : p. 991433 . OpenUrl 17. ↵ Talari , K. and M. Goyal , Retrospective studies-utility and caveats . J R Coll Physicians Edinb , 2020 . 50 ( 4 ): p. 398 – 402 . OpenUrl 18. ↵ Río , J. , et al. , Treatment response scoring systems to assess long-term prognosis in self-injectable DMTs relapsing-remitting multiple sclerosis patients . J Neurol , 2022 . 269 ( 1 ): p. 452 – 459 . OpenUrl 19. ↵ Gill , A. Disease Activity in People Living with MS and NMOSD Exposed to Immune Checkpoint Inhibitors: A Multi-Institutional Study . in Consortium of Multiple Sclerosis Centers Annual Meeting . 2024 . Nashville, TN . View the discussion thread. Back to top Previous Next Posted June 13, 2024. Download PDF Supplementary Material Data/Code Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Neurologic outcomes in people with multiple sclerosis treated with immune checkpoint inhibitors for oncologic indications Message Subject (Your Name) has forwarded a page to you from medRxiv Message Body (Your Name) thought you would like to see this page from the medRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Neurologic outcomes in people with multiple sclerosis treated with immune checkpoint inhibitors for oncologic indications Carson M. Quinn , Prashanth Rajarajan , Alexander Gill , Hannah Kopinsky , Andrew B. Wolf , Celeste Soares De Camargo , Jessica Lamb , Tamar Bacon , Joseph Murray , John C. Probasco , Kristin Galetta , Daniel Kantor , Patricia K. Coyle , Vikram Bhise , Enrique Alvarez , Sarah Conway , Shamik Bhattacharyya , Ilya Kister medRxiv 2024.06.13.24308608; doi: https://doi.org/10.1101/2024.06.13.24308608 Share This Article: Copy Citation Tools Neurologic outcomes in people with multiple sclerosis treated with immune checkpoint inhibitors for oncologic indications Carson M. Quinn , Prashanth Rajarajan , Alexander Gill , Hannah Kopinsky , Andrew B. Wolf , Celeste Soares De Camargo , Jessica Lamb , Tamar Bacon , Joseph Murray , John C. Probasco , Kristin Galetta , Daniel Kantor , Patricia K. Coyle , Vikram Bhise , Enrique Alvarez , Sarah Conway , Shamik Bhattacharyya , Ilya Kister medRxiv 2024.06.13.24308608; doi: https://doi.org/10.1101/2024.06.13.24308608 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Neurology Subject Areas All Articles Addiction Medicine (574) Allergy and Immunology (865) Anesthesia (304) Cardiovascular Medicine (4462) Dentistry and Oral Medicine (445) Dermatology (383) Emergency Medicine (611) Endocrinology (including Diabetes Mellitus and Metabolic Disease) (1517) Epidemiology (15251) Forensic Medicine (31) Gastroenterology (1132) Genetic and Genomic Medicine (6621) Geriatric Medicine (669) Health Economics (1002) Health Informatics (4564) Health Policy (1372) Health Systems and Quality Improvement (1617) Hematology (544) HIV/AIDS (1272) Infectious Diseases (except HIV/AIDS) (15938) Intensive Care and Critical Care Medicine (1107) Medical Education (624) Medical Ethics (147) Nephrology (670) Neurology (6643) Nursing (346) Nutrition (1001) Obstetrics and Gynecology (1149) Occupational and Environmental Health (957) Oncology (3350) Ophthalmology (981) Orthopedics (369) Otolaryngology (421) Pain Medicine (436) Palliative Medicine (130) Pathology (665) Pediatrics (1698) Pharmacology and Therapeutics (694) Primary Care Research (714) Psychiatry and Clinical Psychology (5465) Public and Global Health (9259) Radiology and Imaging (2212) Rehabilitation Medicine and Physical Therapy (1372) Respiratory Medicine (1198) Rheumatology (598) Sexual and Reproductive Health (716) Sports Medicine (533) Surgery (715) Toxicology (100) Transplantation (289) Urology (265) (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'a03c438e19cc8e2e',t:'MTc4MDEyODY0Mg=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();