scholarly journals Autoimmune Encephalitis Related to Cancer Treatment with Immune Checkpoint Inhibitors: Systematic Review

2020 ◽  
Author(s):  
Vardan Nersesjan ◽  
Oskar McWilliam ◽  
Lars-Henrik Krarup ◽  
Daniel Kondziella
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Autoimmune Encephalitis ◽  
Cochrane Library ◽  
Fluid Analysis ◽  
Heterogenous Group ◽  
The Cochrane Library ◽  
Common Laboratory ◽  
Game Changer

BACKGROUND. Immune checkpoint inhibitors (ICPI) are a game changer in the treatment of various metastasized cancers, but emerging reports of adverse events, including ICPI-associated autoimmune encephalitis (ICPI-AIE), are concerning. We aimed to collect all published cases of ICPI-AIE to identify the salient clinical and laboratory features of this disorder. METHODS. We searched PubMed, The Cochrane Library and Embase for ICPI-AIE cases from the first description in 2015 until 01/2020 using standard bibliographic measures including PRISMA guidelines and pre-registration with PROSPERO (CRD42019139838). RESULTS. Thirty-nine studies met inclusion criteria, resulting in 54 ICPI-AIE patients (mean age 58.6 years; 43% females). Common cancers included melanoma (30%) and non-small cell lung cancer (30%). Brain metastases were found in 16 patients (30%). The most frequent ICPI was nivolumab (61%). Onset of ICPI-AIE occurred on average after 3.5 treatment cycles, but very early and late presentations were common. Non-limbic AIE was roughly twice as frequent as limbic AIE (p<0.05). The most common laboratory abnormalities included bitemporal FLAIR lesions on MRI, continuous slow waves and diffuse slowing on EEG, and monocytic pleocytosis on cerebrospinal fluid analysis. Of note, intraneuronal antibodies were more frequent than neuronal surface antibodies, and logistic regression identified the presence of intracellular antibodies as a significant predictor for lack of improvement after 1st line immunotherapy (p<0.05). CONCLUSIONS. ICPI-AIE consists of a heterogenous group of conditions. Neurologists will likely encounter ICPI-AIE more often in the future, but important unresolved questions include the exact pathophysiological mechanisms, the epidemiology and the best treatment approaches associated with ICPI-AIE.

Autoimmune Encephalitis Related to Cancer Treatment With Immune Checkpoint Inhibitors: Systematic Review

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012122
Author(s):  
Vardan Nersesjan ◽  
Oskar McWilliam ◽  
Lars-Henrik Krarup ◽  
Daniel Kondziella
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Autoimmune Encephalitis ◽  
Cochrane Library ◽  
Cerebrospinal Fluid Analysis ◽  
Fluid Analysis ◽  
Heterogenous Group ◽  
The Cochrane Library ◽  
Common Laboratory

OBJECTIVE:To determine the clinical and laboratory features of immune checkpoint inhibitor (ICPI)-associated autoimmune encephalitis (ICPI-AIE), an increasingly recognized adverse event with ICPI treatment.METHODS.We searched PubMed, The Cochrane Library and Embase for ICPI-AIE cases from the first description in 2015 until 01/2020 using standard bibliographic measures including PRISMA guidelines and pre-registration with PROSPERO (CRD42019139838).RESULTS.Thirty-nine studies met inclusion criteria, resulting in 54 ICPI-AIE patients (mean age 58.6 years; 43% females). Common cancers included melanoma (30%) and non-small cell lung cancer (30%). Brain metastases were found in 16 patients (30%). The most frequent ICPI was nivolumab (61%). Onset of ICPI-AIE occurred after a median of 3.5 treatment cycles, but very early and late presentations were common. Non-limbic AIE was roughly twice as frequent as limbic AIE (p<0.05). The most common laboratory abnormalities included bitemporal FLAIR lesions on MRI, continuous slow waves and diffuse slowing on EEG, and monocytic pleocytosis on cerebrospinal fluid analysis. Of note, intraneuronal antibodies were more frequent than neuronal surface antibodies, and a significant predictor for lack of improvement after 1st line immunotherapy (p<0.05).CONCLUSIONS.ICPI-AIE consists of a heterogenous group of conditions. Neurologists will likely encounter ICPI-AIE more often in the future, but important unresolved questions include the exact pathophysiological mechanisms, the epidemiology and the best treatment approaches associated with ICPI-AIE.

Autoimmune encephalitis associated with Ma2 antibodies and immune checkpoint inhibitor therapy

2020 ◽  
Vol 20 (3) ◽  
pp. 256-259 ◽  
Author(s):  
Shane Lyons ◽  
Ronan Joyce ◽  
Patrick Moynagh ◽  
Luke O'Donnell ◽  
Silive Blazkova ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Autoimmune Encephalitis ◽  
Advanced Malignancy ◽  
Temporal Lobes ◽  
Stage 4 ◽  
Fluid Attenuated Inversion Recovery ◽  
Checkpoint Inhibitor Therapy

Immune checkpoint inhibitors have transformed the treatment of advanced malignancy, while increasing the risk of immune-related adverse events. A 56-year-old woman who had received nivolumab for stage 4 renal cell carcinoma subsequently developed altered behaviour, memory deficits and worsening of previously stable epilepsy. MR scan of the brain showed bilateral FLAIR (fluid-attenuated inversion recovery) hyperintensity of the mesial temporal lobes, and there were anti-Ma2 antibodies in both serum and cerebrospinal fluid. She was treated with corticosteroids but developed further clinical relapses requiring immunoglobulin and rituximab. The immune-related adverse events relating to immune checkpoint inhibitors are an emerging challenge for the neurologist. Some cases are refractory and require serial immunosuppression.

scholarly journals Immune checkpoint inhibitor induced autoimmune encephalitis in a patient with metastatic melanoma

2020 ◽  
Vol 7 (3) ◽  
pp. 1
Author(s):  
Nivedita Sudhekar ◽  
Binoy Yohannan ◽  
Mark Feldman
Keyword(s):  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Early Recognition ◽  
Combined Therapy ◽  
Autoimmune Encephalitis ◽  
The Body

Background: Immune checkpoint inhibitors have changed the therapeutic milieu for patients with metastatic melanoma. However, their use may promote autoimmunity in virtually any organ in the body due to the blockade of intrinsic immune down regulators such as cytotoxic T-lymphocyte antigen- 4 (CTLA-4), programmed cell death 1 (PD1) or its ligand (PDL1). Immune mediated adverse neurological events are rare with these agents, however, and are seen in < 1% of treated patients. We report a patient with immune checkpoint inhibitor associated autoimmune encephalitis, with complete clinical recovery after treatment.Case Report: A 49-year-old female with metastatic melanoma currently on nivolumab therapy but recently on ipilimumab/nivolumab combined therapy presented with a new headache. She also reported associated confusion, loss of balance, personality changes and language difficulty. Magnetic resonance imaging of the brain did not reveal any evidence of metastasis, infarct, meningitis, or encephalitis. Lumbar puncture revealed an elevated protein level and pleocytosis, with a normal glucose level. She was started on empiric glucocorticoid therapy with a presumptive diagnosis of immune checkpoint inhibitor associated autoimmune encephalitis. She improved considerably by day 3 of treatment with complete resolution of neurological symptoms by day 5.Conclusion: Immune checkpoint inhibitors are increasingly important in cancer immunotherapy as they can cause sustained remissions in patients with metastatic melanoma and other malignancies. Because these drugs block immune-regulatory targets, they can lead to enhanced activation of immune system resulting in immune-related adverse events. Autoimmune encephalitis is a rare immune-related adverse event associated with immune checkpoint inhibitors. The incidence of autoimmune encephalitis is higher with combination or sequential CTLA-4 (ipilimumab) and PD1(nivolumab) inhibitor therapy than with monotherapy. With more widespread use of immunotherapy, it is important for clinicians to be aware of this rare and reversible cause of encephalitis. Early recognition and prompt initiation of immunosuppressive therapy with glucocorticoids is essential to enhance neurological recovery.

scholarly journals Predictive Biomarkers for Outcomes of Immune Checkpoint Inhibitors (ICIs) in Melanoma: A Systematic Review

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6366
Author(s):  
Joosje C. Baltussen ◽  
Marij J. P. Welters ◽  
Elizabeth M. E. Verdegaal ◽  
Ellen Kapiteijn ◽  
Anne M. R. Schrader ◽  
...  
Keyword(s):  
Systematic Review ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Unmet Need ◽  
Predictive Biomarkers ◽  
Suppressor Cells ◽  
Cochrane Library ◽  
Durable Response ◽  
Melanoma Patients

Immune checkpoint inhibitors (ICIs) have strongly improved the survival of melanoma patients. However, as durable response to ICIs are only seen in a minority, there is an unmet need to identify biomarkers that predict response. Therefore, we provide a systematic review that evaluates all biomarkers studied in association with outcomes of melanoma patients receiving ICIs. We searched Pubmed, COCHRANE Library, Embase, Emcare, and Web of Science for relevant articles that were published before June 2020 and studied blood, tumor, or fecal biomarkers that predicted response or survival in melanoma patients treated with ICIs. Of the 2536 identified reports, 177 were included in our review. Risk of bias was high in 40%, moderate in 50% and low in 10% of all studies. Biomarkers that correlated with response were myeloid-derived suppressor cells (MDSCs), circulating tumor cells (CTCs), CD8+ memory T-cells, T-cell receptor (TCR) diversity, tumor-infiltrating lymphocytes (TILs), gene expression profiling (GEP), and a favorable gut microbiome. This review shows that biomarkers for ICIs in melanoma patients are widely studied, but heterogeneity between studies is high, average sample sizes are low, and validation is often lacking. Future studies are needed to further investigate the predictive utility of some promising candidate biomarkers.

scholarly journals A Network Comparison on Safety Profiling of Immune Checkpoint Inhibitors in Advanced Lung Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi-Dan Yan ◽  
Jiu-Jie Cui ◽  
Jie Fu ◽  
Ying-Jie Su ◽  
Xiao-Yu Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Advanced Lung Cancer ◽  
Cochrane Library ◽  
Public Attention ◽  
Grade 3

BackgroundImmune checkpoint inhibitors (ICIs) have become one of the standard treatment options for advanced lung cancer. However, adverse events (AEs), particularly immune–related AEs (irAEs), caused by these drugs have aroused public attention. The current network meta-analysis (NMA) aimed to compare the risk of AEs across different ICI–based regimens in patients with advanced lung cancer.MethodsWe systematically searched the PubMed, EMBASE, and Cochrane Library databases (from inception to 19 April 2021) for relevant randomized controlled trials (RCTs) that compared two or more treatments, with at least one ICI administered to patients with advanced lung cancer. The primary outcomes were treatment–related AEs and irAEs, including grade 1–5 and grade 3–5. The secondary outcomes were grade 1–5 and grade 3–5 irAEs in specific organs. Both pairwise and network meta-analyses were conducted for chemotherapy, ICI monotherapy, ICI monotherapy + chemotherapy, dual ICIs therapy, and dual ICIs + chemotherapy for all safety outcomes. Node–splitting analyses were performed to test inconsistencies in network. Sensitivity analyses were adopted by restricting phase III RCTs and studies that enrolled patients with non–small cell lung cancer.ResultsOverall, 38 RCTs involving 22,178 patients with advanced lung cancer were enrolled. Both pooled incidence and NMA indicated that treatments containing chemotherapy increased the risk of treatment–related AEs when compared with ICI-based regimens without chemotherapy. As for grade 1–5 irAEs, dual ICIs + chemotherapy was associated with the highest risk of irAEs (probability in ranking first: 50.5%), followed by dual-ICI therapy (probability in ranking second: 47.2%), ICI monotherapy (probability in ranking third: 80.0%), ICI monotherapy + chemotherapy (probability in ranking fourth: 98.0%), and finally chemotherapy (probability in ranking fifth: 100.0%). In grade 3–5 irAEs, subtle differences were observed; when ranked from least safe to safest, the trend was dual ICIs therapy (60.4%), dual ICIs + chemotherapy (42.5%), ICI monotherapy (76.3%), ICI monotherapy + chemotherapy (95.0%), and chemotherapy (100.0%). Furthermore, detailed comparisons between ICI–based options provided irAE profiles based on specific organ/system and severity.ConclusionsIn consideration of overall immune–related safety profiles, ICI monotherapy + chemotherapy might be a better choice among ICI–based treatments for advanced lung cancer. The safety profiles of ICI–based treatments are various by specific irAEs and their severity.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42021268650

scholarly journals The Prediction Potential of the Pretreatment Lung Immune Prognostic Index for the Therapeutic Outcomes of Immune Checkpoint Inhibitors in Patients With Solid Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Hui Liu ◽  
Xiao-Li Yang ◽  
Xiao-Yun Yang ◽  
Zhao-Ru Dong ◽  
Zhi-Qiang Chen ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Prognostic Index ◽  
Cochrane Library ◽  
Solid Cancer ◽  
Primary Analysis ◽  
Therapeutic Outcomes

BackgroundThe lung immune prognostic index (LIPI) is recently developed to predict immune checkpoint inhibitors (ICIs) treatment outcomes for non-small cell lung cancer. However, its predictive value for other types of cancer remained unclear. This meta-analysis aimed to evaluate the association between pretreatment LIPI score and therapeutic outcomes in cancer patients treated with ICIs.MethodsWe searched PubMed, Cochrane Library literature databases and EMBASE for abstracts and full-text articles published from the inception of the database until 16th, Nov 2020. Meta-analyses were performed separately for progression-free survival (PFS) and overall survival (OS) by using the random-effects model.ResultsA total of 12 studies involving 4883 patients receiving ICIs treatment were identified for the primary analysis. The pooled results implied that compared with good LIPI score groups, patients with poor or intermediate LIPI score were significantly associated with worse OS (HR=3.33, 95%CI 2.64-4.21, P &lt; 0.001, I2 = 64.2%; HR=1.71, 95%CI 1.43-2.04, P &lt; 0.001, I2 = 43.6%, respectively) and PFS (HR=2.73,95%CI 2.00-3.73, P &lt; 0.001, I2 = 78.2%; HR=1.43, 95%CI 1.28-1.61, P &lt; 0.001, I2 = 16.3%, respectively). Also, for 1873 patients receiving chemotherapy, a poor LIPI score was significantly associated with worse OS (HR=2.30, 95%CI 1.73-3.07, P &lt; 0.001; I2 = 56.2%) and PFS (HR=1.92,95%CI 1.69-2.17; P &lt; 0.001; I2 = 0.0%) compared with good LIPI score groups.ConclusionsA good LIPI score was significantly correlated with improved OS and PFS in cancer patients receiving ICIs or chemotherapy, regardless of the types of cancer.

Infections in cancer patients treated with immune checkpoint inhibitors: Data from randomized trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2637-2637
Author(s):  
Cinzia Solinas ◽  
Anna Maria Morelli ◽  
Andrea Luciani ◽  
Antonio Ghidini ◽  
Fausto Petrelli
Keyword(s):  
Clinical Trials ◽  
Cancer Patients ◽  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Randomized Trials ◽  
Randomized Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Cochrane Library ◽  
And Control

2637 Background: Febrile neutropenia and infections are well studied complications of chemotherapy (CT) and some targeted agents employed in oncology. Less is known about the risk of infection associated with the use of immune checkpoint inhibitors (ICIs) in cancer patients. The present systematic review and meta-analysis was performed to address this question in patients diagnosed with solid tumors enrolled in randomized trials employing ICIs as experimental treatment. Methods: The Cochrane Library, EMBASE, and Pubmed databases were searched from inception through December 1st, 2020. Randomized clinical trials comparing any ICI alone, with CT, or with other agents vs CT, placebo, or other agents in patients with solid tumors were included. Two independent reviewers used a standardized data extraction and quality assessment form. Discordant cases were discussed with a third independent investigator. The following information was extracted: baseline study characteristics, including the primary tumor, author, year of publication, type of trial, type of disease, and the type of therapy (experimental and control arms); and the incidence of any-grade (grades [G] 1–5), low-grade (G1–2), and high-grade (G3–4), fatal event (G5) infections, and type of event. Random or fixed-effect models were used according to the statistical heterogeneity. Results: 36 randomized clinical trials were deemed eligible. The total population reached 21451 patients. In the pooled analysis, the use of ICIs was associated with a similar risk of all-grade infections (relative risk, RR = 1.02; 95% CI 0.84–1.24; P = 0.85) compared to non-ICI treatments (G1-5 events: 9.6 vs. 8.3%). When the ICIs alone arms were compared to CT, the experimental arms were associated with a 42% less risk of all-grade infections (RR = 0.58, 95% CI 0.4–0.85; P = 0.01; N = 18 studies). Compared to CT, the combination of ICIs and CT increased the risk of all-grade infections (RR = 1.37, 95% CI 1.23–1.53; P < 0.01; N = 13 studies) and severe infections (RR = 1.52, 95% CI 1.17–1.96; P < 0.01; N = 12 studies). Fatal infections were similar in the experimental and control arms (0.5%). Conclusions: In patients with advanced solid tumors, when ICIs were administered with CT, the risk of all-grade and G3-5 infections was significantly increased. Compared to CT alone, ICIs were safer and their use should be recommended for frail patients. Further studies are required to identify high-risk patients and evaluate the need for CT dose reduction or prophylactic myeloid growth factors use.

The safety and efficacy of immune-checkpoint inhibitors in patients with cancer and pre-existing autoimmune diseases

Immunotherapy ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 527-539
Author(s):  
Chunlan Wu ◽  
Li Zhong ◽  
Qing Wu ◽  
Shaowei Lin ◽  
Xianhe Xie
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Cochrane Library ◽  
Antitumor Effects ◽  
Safety And Efficacy ◽  
Patients With Cancer ◽  
Early Use ◽  
Grade 3

Objective: This study aims at investigating the safety and efficacy of immune-checkpoint inhibitors (ICIs) in patients with cancer and pre-existing autoimmune disease (AID). Materials & methods: PubMed, Embase and Cochrane Library were searched for relevant studies. The primary end points of the study were immunotoxicity and cancer response. Results: At the early use of ICIs, compared with those with active AID, grade 3–4 AID flare occurred more frequently in patients with inactive AID after treatment with ICIs; and the incidence of grade 3–4 immunotoxic effects was significantly lower in patients undergoing immunosuppressive therapy than those without corresponding treatment. In addition, patients with worsening AID generally obtained a better objective response than those without a flare. Conclusion: This study demonstrates that the toxic effects induced by immunotherapy are generally manageable in patients with cancer and pre-existing AID, some of whom even achieve satisfactory antitumor effects in clinical practice.

scholarly journals Association of Steroids Use with Survival in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 546 ◽  
Author(s):  
Fausto Petrelli ◽  
Diego Signorelli ◽  
Michele Ghidini ◽  
Antonio Ghidini ◽  
Elio Gregory Pizzutilo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Symptom Control ◽  
Cochrane Library ◽  
Risk Of Death ◽  
Increased Risk

Immune checkpoint inhibitors (ICIs) can elicit toxicities by inhibiting negative regulators of adaptive immunity. Sometimes, management of toxicities may require systemic glucocorticoids. We performed a systematic review and meta-analysis of published studies to evaluate the correlation between steroids use, overall survival (OS), and progression-free survival (PFS) in cancer patients treated with ICIs. Publications that compared steroids with non-steroid users in cancer patients treated with ICIs from inception to June 2019 were identified by searching the EMBASE, PubMed, SCOPUS, Web of Science, and Cochrane Library databases. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Patients (studies, n = 16; patients, n = 4045) taking steroids were at increased risk of death and progression compared to those not taking steroids (HR = 1.54, 95% CI: 1.24–1.91; p = 0.01 and HR = 1.34, 95% CI: 1.02–1.76; p = 0.03, respectively). The main negative effect on OS was associated with patients taking steroids for supportive care (HR = 2.5, 95% CI 1.41–4.43; p < 0.01) or brain metastases (HR = 1.51, 95% CI 1.22–1.87; p < 0.01). In contrast, steroids used to mitigate adverse events did not negatively affect OS. In conclusion, caution is needed when steroids are used for symptom control. In these patients, a negative impact of steroid use was observed for both OS and PFS.

Sign in / Sign up

Export Citation Format

Share Document