scholarly journals Immune-related adverse events of COVID-19 vaccination in skin cancer patients receiving immune-checkpoint inhibitor treatment

2021 ◽  
Author(s):  
Sophia B. Strobel ◽  
Devayani Machiraju ◽  
Katharina A. Kälber ◽  
Jessica C. Hassel
Keyword(s):  
Side Effects ◽  
Skin Cancer ◽  
Adverse Events ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Vaccine Type ◽  
Small Cohort ◽  
Grade 3 ◽  
Few Data

AbstractTo date, few data are available regarding Adverse events (AEs) in cancer patients who are vaccinated for coronavirus disease 2019 (COVID-19) while being actively treated with Immune-checkpoint inhibitors (ICIs). We aimed to assess the safety of COVID-19 vaccines approved in Germany. Specifically, we investigated the frequency of general side effects and immune-related AEs of COVID-19 vaccination. A triage survey was used to collect the following information for patients with metastatic skin cancer: vaccine type, date of receipt of each dose of vaccine, and self-reported side effects. Clinical data were retrieved from the patients’ medical records. Of 130 patients with metastatic skin cancer, 89 patients were on immunotherapy and received COVID-19 vaccination. Of these 89 patients (median age: 64 years; 57 [64%] men), 89% had melanoma, and 71% received ICI therapy with a PD-1 antibody. Eighty-eight percent received an mRNA-based COVID-19 vaccination. The median follow-up time was 125 days after the first vaccination, and 84 days after the second. The most common observed side effects were mild to moderate pain at the injection site (40%), followed by fatigue (24%). Grade 3 irAEs were reported in eight patients, seven of whom were on nivolumab plus ipilimumab combination treatment. Of the 19 patients vaccinated within 72 h before/after ICI, five developed irAEs within 17 days (1–17 days). This small cohort study suggests that approved COVID-19 vaccinations are safe for use in cancer patients receiving ICIs. However, some precautions should be taken, especially regarding the timing of vaccination and ICI treatment.

scholarly journals 807 Immunotherapy related adverse events: a single center experience

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A844-A844
Author(s):  
Wei Yang ◽  
Julie Rowe ◽  
Sophia Lee ◽  
Jing Zhang ◽  
Mohammad Rahbar
Keyword(s):  
Renal Function ◽  
Adverse Events ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Study Data ◽  
List Type ◽  
Prior Chemotherapy ◽  
Grade 3

BackgroundAs the role of immune checkpoint inhibitors (ICIs) expands in many malignancies, including hepatocellular carcinoma (HCC), a better understanding of the predictors of immunotherapy-related adverse events (irAEs) is needed due to the complexity that ICIs add to patient care.1–5MethodsWe conducted a single-institution retrospective chart review for cancer patients of any type who received at least one ICI between January 2015 and December 2020. Demographic, social, cancer-related, laboratory, and treatment variables were collected, along with irAE data. Exploratory statistical analysis was performed to find predictors of increased irAEs.ResultsA total of 342 patients were included in the study: 133 women and 209 men. Median age was 65 years. The most common cancers were lung (110, 32.07%), kidney (51, 14.87%), and HCC (43, 12.54%). All patients received at least one dose of ICI (table 1); 11 received combination ICIs. One hundred and two (26.53%) patients developed irAEs of any grade (table 2). Nineteen patients (5.56%) had a grade 3 or 4 irAE; 20 patients required systemic steroids. No biologics were used for the management of severe irAEs. Patients who received prior chemotherapy were less likely to develop irAEs (odds ratio [OR] = 0.42, p = 0.0006). A history of hyperthyroidism or hypothyroidism was associated with more irAEs (p = 0.011). Combination ICI led to more irAEs overall (OR = 2.91, p = 0.043), as well as grade 3 or 4 events (OR = 5.32, p = 0.008). A trend toward more grade 3 or 4 events occurred in HCC patient (OR = 2.78, p = 0.06). Older patients showed a trend toward more irAEs (p = 0.08).Worse peri-treatment renal function was associated with an increased risk of irAE (OR = 1.86, p = 0.047). A higher peri-treatment hemoglobin nadir was associated with a lower risk of irAE (OR = 0.45, p = 0.07). Several other variables had ORs or confidence intervals close to 1, including number of sessions of ICI and higher baseline AST.ConclusionsPrior chemotherapy, worse renal function, and thyroid dysfunction were associated with irAEs, whereas higher hemoglobin nadir was protective against irAE. Unlike the current literature, our study included a large number of HCC patients. The higher irAE incidence in our study could be associated with this higher number of HCC patients; however, further studies are needed.ReferencesBrahmer JR, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline. JCO 2018;36:1714–1768.National Comprehensive Cancer Network. Management of Immunotherapy-Related Toxicities, 2021. https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf.Kartolo A, Sattar J, Sahai V, Baetz T, Lakoff JM. Predictors of immunotherapy-induced immune-related adverse events. Curr Oncol 2018;25:e403–e410.Suresh K, et al. Pneumonitis in non–small cell lung cancer patients receiving immune checkpoint immunotherapy: incidence and risk factors. Journal of Thoracic Oncology 2018;13:1930–1939.Colen RR, et al. Radiomics to predict immunotherapy-induced pneumonitis: proof of concept. Invest New Drugs 2018;36:601–607.Ethics ApprovalThe study involving retrospective review of patient records was approved under the Institutional Review Board. All records identifying the patient was be kept confidential and, to the extent permitted by the applicable laws and/or regulations, were not be made publicly available. Patient names will not be supplied to third parties. A unique study number will be assigned to each patient. Study data stored electronically will be stored in a password-protected, encrypted computers. Paper study data will be maintained by the primary investigators in the locked research offices.ConsentN/AAbstract 807 Table 1Immune checkpoint inhibitors receivedAbstract 807 Table 2irAE incidence

scholarly journals Questionnaire-based detection of immune-related adverse events in cancer patients treated with PD-1/PD-L1 immune checkpoint inhibitors

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Luisa Maria Griewing ◽  
Claudia Schweizer ◽  
Philipp Schubert ◽  
Sandra Rutzner ◽  
Markus Eckstein ◽  
...  
Keyword(s):  
Adverse Events ◽  
Cancer Patients ◽  
Weight Change ◽  
Immune Checkpoint ◽  
Detection Rate ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Patient Questionnaire ◽  
Organ Specific ◽  
Tumor Entities

Abstract Background Immune checkpoint inhibitors (ICI) have become standard treatment in different tumor entities. However, safe treatment with ICI targeting the PD-1/PD-L1 axis requires early detection of immune-related adverse events (irAE). There exist different questionnaires of drug manufacturers for the detection of irAE that have not been validated so far. Methods The prospective non-interventional ST-ICI trial studied treatment with PD-1/PD-L1 ICI alone or combined with radiotherapy. In the current analysis, the detection rate of self-reported irAE with a patient questionnaire containing 41 different questions was compared to clinician-reported irAE. Results Between April 2017 and August 2019, a total of 104 patients were prospectively enrolled. NSCLC (44%) and HNSCC (42%) were the most frequent tumor entities. A total of 784 questionnaires were collected. A total of 29 irAE were reported by clinicians. The most frequent irAE was hypothyroidism (9%), followed by skin reactions (5%), hepatitis (4%), diarrhea (3%), and pneumonitis (3%). Questions that became significantly more often positive at time points of clinician-reported irAE were “weight change”, “difficulty to grip things”, “bloody or mucous stool” and “insomnia”. Self-reported organ-specific questions detected at least 50% of clinician-reported irAE of gastrointestinal, lung, endocrine, and skin irAE. It was not possible to detect hepatic irAE with the questionnaire. Conclusion Questionnaires can help to detect gastrointestinal, lung, endocrine, or skin irAE, but not hepatic irAE. Questions on “weight change” and “insomnia” may help to increase the detection rate of irAE, besides organ-specific questions. These results are a valuable contribution to the future development of a specific and practicable questionnaire for early self-reported detection of irAE during ICI therapy in cancer patients. Trial registration ClinicalTrials.gov, NCT03453892. Registered on 05 March 2018.

scholarly journals 522 Transcriptomic changes in cancer patients treated with immune-checkpoint inhibitors

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A552-A552
Author(s):  
Dmitrii Shek ◽  
Bo Gao ◽  
Joey Lai ◽  
Won-Hee Yoon ◽  
Tania Moujaber ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Differentially Expressed Genes ◽  
Immune Checkpoint ◽  
Functional Annotation ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Link Type ◽  
Pre Treatment ◽  
Grade 3 ◽  
Transcriptomic Changes

BackgroundImmune-checkpoint inhibitors (ICIs) are monoclonal antibodies that block inhibitory CTLA-4/PD-1 signalling pathways and thus boost cytotoxic T cell antitumor activity. ICIs have been proven effective in various malignancies, but there is a lack of knowledge regarding factors associated with ICI efficacy and safety. This study aims to examine transcriptomic changes in cancer patients treated with ICIs and their potential association with related clinical outcomes.MethodsThis is a prospective multicentre cohort study (NCT04631731) recruiting cancer patients treated with (1) ICI monotherapy; (2) ICI dual therapy; (3) ICI + kinase inhibitor; (4) ICI + platinum-doublet chemotherapy. Peripheral blood is collected at baseline and 6–8 weeks after first ICI treatment as well as after the development of immune-related adverse events (irAEs, grade 2 and higher). Whole transcriptome sequencing (Novaseq S4 300 cycle lane, Illumina) was performed and followed by functional annotation using the ConsensusPath-DB platform.Results22 patients were recruited to the study and had paired blood taken. Two patients had developed grade 3–4 irAEs. RNA sequencing analysis identified 3,000 genes that were significantly dysregulated at week 6–8 after ICI commencement as compared to pre-treatment in n=20 recruited patients without irAEs (figure 1). Functional annotation established that 132 pathways were associated with the identified set of dysregulated genes. Among them: (1) pre-NOTCH processing in Golgi, (2) Interleukin-15 signalling; (3) STAT5 activation, and (4) RORA activation of gene expression possessed a gene set enrichment of at least 80% and p<0.01. In 2 patients with grade 3 immune-mediated hepatitis, both treated with combination of CTLA-4/PD-1 inhibitors, analysis revealed that 360 and 325 were 2-fold up- and downregulated respectively upon onset of toxicity as compared to both pre-treatment and 1-week post-steroid treatment. Interestingly, this gene set possessed minimal overlap when compared to genes dysregulated in patients without irAEs. Moreover, functional annotation established different pathways that were associated with toxicity. The highest enrichment scores belonged to pathways regulating cell cycle and apoptotic pathways driven by CDC25A, p53 and BCL-2, among others.Abstract 522 Figure 1Volcano plot representing the differentially expressed genesThe figure representing differentially expressed genes elucidated in this pilot study. N=3000 genes were significantly dysregulated between pre- and week 6–8 post-IO commencement.ConclusionsThe preliminary analysis of the first 22 patients recruited to NCT04631731 confirms that ICI treatment interferes with expression of coding and non-coding RNAs. Importantly, patients with and without irAEs show different patterns of transcriptomic changes as well as variability among activated cellular pathways. This data emphasises the need for further exploration and validation of transcriptomic changes in a larger cohort. In the near future, RNA signatures may be utilised as biomarkers to rapidly and accurately diagnose irAEs.AcknowledgementsN/ATrial RegistrationClinicalTrials.Gov identification number: NCT04631731ReferencesN/AEthics ApprovalThis study has been approved by the Western Sydney Local Health District (WSLHD) Human Research Ethics Committee on the November 9th, 2020 to be conducted at Blacktown and Westmead Public Hospitals of the WSLHD, Sydney, NSW, Australia.ConsentEach participant recruited to this translational study has provided written consent approved on the November 6th, 2020 (MASTER version) by the WSLHD HREC.

scholarly journals Systematic Review and Network Meta-Analysis of Immune Checkpoint Inhibitors in Combination with Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3629
Author(s):  
Hsiao-Ling Chen ◽  
Yu-Kang Tu ◽  
Hsiu-Mei Chang ◽  
Tai-Huang Lee ◽  
Kuan-Li Wu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Small Cell ◽  
Randomized Controlled ◽  
Extensive Stage ◽  
Grade 3

Patients with extensive-stage small cell lung cancer (ED-SCLC) have a very short survival time even if they receive standard cytotoxic chemotherapy with etoposide and platinum (EP). Several randomized controlled trials have shown that patients with ED-SCLC who received a combination of EP plus immune checkpoint inhibitors (ICIs) had superior survival compared with those who received EP alone. We conducted a systematic review and network meta-analysis to provide a ranking of ICIs for our primary endpoints in terms of overall survival (OS), progression free survival (PFS), and objective response rate (ORR), as well as our secondary endpoint in terms of adverse events. The fractional polynomial model was used to evaluate the adjusted hazard ratios for the survival indicators (OS and PFS). Treatment rank was estimated using the surface under the cumulative ranking curve (SUCRA), as well as the probability of being best (Prbest) reference. EP plus nivolumab, atezolizumab or durvalumab had significant benefits compared with EP alone in terms of OS (Hazard Ratio HR = 0.67, 95% Confidence Interval CI = 0.46–0.98 for nivolumab, HR = 0.70, 95% CI = 0.54–0.91 for atezolizumab, HR = 0.73, 95% CI = 0.59–0.90 for durvalumab) but no significant differences were observed for pembrolizumab or ipilimumab. The probability of nivolumab being ranked first among all treatment arms was highest (SCURA = 78.7%, Prbest = 46.7%). All EP plus ICI combinations had a longer PFS compared with EP alone (HR = 0.65, 95% CI = 0.46–0.92 for nivolumab, HR = 0.77, 95% CI = 0.61–0.96 for atezolizumab, HR = 0.78, 95% CI = 0.65–0.94 for durvalumab, HR = 0.75, 95% CI = 0.61–0.92 for pembrolizumab), and nivolumab was ranked first in terms of PFS (SCURA = 85.0%, Prbest = 66.8%). In addition, nivolumab had the highest probability of grade 3–4 adverse events (SUCRA = 84.8%) in our study. We found that nivolumab had the best PFS and OS in all combinations of ICIs and EP, but nivolumab also had the highest probability of grade 3–4 adverse events in our network meta-analysis. Further head-to head large-scale phase III randomized controlled studies are needed to verify our conclusions.

Immune-related adverse events associated with immune checkpoint inhibitors in patients with cancer

2020 ◽  
pp. 030089162095346
Author(s):  
Nilay Sengul Samanci ◽  
Duygu Ilke Cikman ◽  
Kerem Oruc ◽  
Sahin Bedir ◽  
Emir Çelik ◽  
...  
Keyword(s):  
Adverse Events ◽  
Health Care Providers ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Early Recognition ◽  
Care Providers ◽  
Patients With Cancer ◽  
Combination Treatments ◽  
Grade 3

Introduction: With the widespread use of immune checkpoint inhibitors (ICIs), we are facing challenges in the management of immune-related adverse events (irAEs). We aimed to characterize the spectrum of toxicity, management, and outcomes for irAEs. Methods: Patients who were treated with at least one ICI in clinical trials, expanded access programs, or routine clinical practice were included. Clinical and laboratory parameters were collected retrospectively to determine the incidence of irAEs, methods of management, and treatment outcomes. Results: A total of 255 patients were screened retrospectively. Of these, 71 (27.8%) patients developed irAEs. More than 2 different types of irAEs were detected in 16 (6.2%) out of 255 patients. A total of 3177 doses were given to 255 patients. In 93 (2.9%) of the 3177 doses, 1 episode of irAEs was experienced. A total of 22 out of 93 (23.7%) episodes were reported as grade 1, 49 (52.7%) as grade 2, 19 (20.4%) as grade 3, and 3 (3.2%) as grade 4. The most frequently seen irAEs were pneumonitis, hepatitis, and hypothyroidism. With regard to treatment, 39 out of 93 episodes (42%) of any grade irAEs occurred after anti–programmed cell death-1 therapy, 47 (50.5%) occurred following administration of anti–programmed death-ligand 1, and 7 (7.5%) occurred after combination treatments. Conclusion: With the increased use of immunotherapeutic agents, increased awareness and early recognition are required for effective management of irAEs. Our experience as a single institution might be of use for health care providers in oncology.

scholarly journals Comparative risk of serious and fatal treatment-related adverse events caused by 19 immune checkpoint inhibitors used in cancer treatment: a network meta-analysis

2020 ◽  
Vol 12 ◽  
pp. 175883592094092 ◽  
Author(s):  
Tingting Liu ◽  
Bo Jin ◽  
Jun Chen ◽  
Hui Wang ◽  
Shuiyu Lin ◽  
...  
Keyword(s):  
Adverse Events ◽  
Cancer Treatment ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Combinatorial Therapy ◽  
Grade 5 ◽  
Comparative Risk ◽  
Grade 3

Background: This network meta-analysis assessed the comparative risk of grade 3–5 and grade 5 treatment-related adverse events (TRAEs) for immune checkpoint inhibitors (ICIs), either alone or in combination with other modalities, for cancer treatment. Methods: PubMed, Embase, Cochrane Library, Web of Science, and recent predominant oncology congresses were searched for relevant phase II and phase III randomized controlled trials (RCTs). As outcomes, grade 3–5, and grade 5 TRAE outcomes were reported as odds ratios and 95% confidence intervals. Results: In 67 RCTs involving 36,422 patients and 19 ICIs, the incidence of grade 3–5 and grade 5 TRAEs was 17.9% and 0.8% with ICI monotherapy and 46.3% and 1.4%, respectively, with combinatorial therapy. Pneumonitis was the most common cause of grade 5 TRAEs following either monotherapy (16.3%) or combinatorial therapy (11.4%). Regarding grade 3–5 TRAEs, atezolizumab + chemotherapy (CT) and antiangiogenic therapy (AT) (atezolizumab + CAT), pembrolizumab + CT, ipilimumab + CT, and atezolizumab + CT were more toxic than any ICI monotherapy, pembrolizumab or nivolumab + radiotherapy (RT), and ICIs dual therapy (durvalumab + tremelimumab and nivolumab + ipilimumab). Tremelimumab, ipilimumab, durvalumab, and pembrolizumab were, however, associated with higher grade 5 TRAEs than combinatorial treatments. Atezolizumab + CAT was the most toxic and nivolumab + RT was the least toxic of combinatorial treatments; among monotherapies, tremelimumab and avelumab were the most and least toxic, respectively. The toxicity ranking changed with type of grade 3–5 TRAEs. Conclusions: Compared with combinatorial therapy, ICI monotherapy caused lower grade 3–5 TRAEs, but some monotherapies resulted in a higher incidence of fatal TRAEs. Atezolizumab + CAT and nivolumab + RT were the most and least toxic of combinatorial treatments, respectively, and tremelimumab and avelumab were the most and least toxic of the monotherapies, respectively.

Liver injury by immune checkpoint inhibitors in patients with hepatocellular carcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 341-341 ◽  
Author(s):  
Nicola Personeni ◽  
Tiziana Pressiani ◽  
Antonio Capogreco ◽  
Arianna Dal Buono ◽  
Antonio D'Alessio ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Injury ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Subsequent Treatment ◽  
Drug Induced ◽  
Increased Risk ◽  
Grade 3

341 Background: In patients with hepatocellular carcinoma (HCC) and baseline liver dysfunction, hepatic immune-related adverse events (HIRAEs) during immunotherapy have not been adequately characterized and their impact on subsequent treatment outcomes is not known. Methods: 40 patients with advanced/unresectable HCC and Child Pugh score A have been enrolled in first and second-line clinical trials of anti-programmed cell death protein 1 (PD-1) monoclonal antibodies (mAbs). HCC etiologies were: hepatitis C (32.5%), hepatitis B (7.5%), alcohol abuse (27.5%), other (32.5%). 7 received anti-PD-1 mAbs alone and 33 received combined regimens that included anti-PD-1 mAbs plus either anti-cytotoxic T lymphocyte antigen 4 (30.4%) or tyrosine kinase inhibitors (TKIs) (54.5%), or both (15.1%). We reviewed their liver function tests and HIRAEs onset was related to time to treatment failure (TTF). Results: Overall, 12 patients (30%) developed grade ≥ 3 hepatitis according to Common Toxicity Criteria for Adverse Events v. 4.03, resulting in 4 cases of grade 2 drug-induced liver injury per DILI Working Group criteria. Time between therapy initiation and hepatitis onset was 1.4 months (0.4-2.8) and median peak aminotransferase (AT) level was 258 IU/L (85-869). Out of 6 permanent treatment discontinuations due to adverse events (AEs), 4 were linked to hepatitis. Higher AT median levels at baseline were significantly linked to grade ≥ 3 hepatitis compared with lower grades (95 IU/L vs. 36 IU/L, respectively; p = 0.008). Etiology, age, treatment did not predict HIRAEs onset. TTF in patients in patients with grade ≥ 3 hepatitis was shorter than in the whole cohort (1.4 vs. 3.8 months, p = 0.041), while overall survival did not differ (p = 0.125). Conclusions: We observed a 30% incidence of clinically significant HIRAEs. HIRAEs represent the most frequent AEs leading to treatment discontinuation in patients with HCC undergoing treatments with immune checkpoint inhibitors. Baseline AT levels may identify patients at increased risk of grade ≥ 3 hepatitis.

Immune checkpoint inhibitor induced hepatitis: Risk factors, outcomes, and impact on survival.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14525-e14525
Author(s):  
Abdul Miah ◽  
Songzhu Zhao ◽  
Sandip H. Patel ◽  
Andrew Johns ◽  
Madison Grogan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Comprehensive Cancer Center ◽  
Rank Test ◽  
Cancer Center ◽  
Grade 3

e14525 Background: Immune checkpoint inhibitors (ICIs) have improved the survival of patients with multiple cancer types, however ICI treatment is associated with a unique set of immune-related adverse events (irAEs) that can affect any organ. Few studies have evaluated the risk factors and outcomes of ICI induced hepatitis (ICIH). Methods: We utilized an institutional database of patients with advanced cancers treated with ICI between 2011 and 2017 at The OSU Comprehensive Cancer Center to identify patients with ICIH. Any patient who received at least one dose of ICI alone or in combination with other systemic therapies either as part of clinical trial or standard of care were included. Clinical data were extracted through chart abstraction. irAEs were graded using the Common Terminology Criteria for Adverse Events v5. Overall survival (OS) was calculated from the date of ICI initiation to death from any cause or the date of the last follow-up. OS with 95% confidence intervals were estimated using the Kaplan–Meier method. OS was also evaluated by occurrence of ICIH using the log-rank test. Results: We identified 1,096 patients treated with at least one dose of ICI. Most common cancers included lung (n=224, 20%) and melanoma (n=342, 31%). The most common ICIs were PD1/L1 (n=774, 71%) and CTLA-4 inhibitors (n=195, 18%). ICIH of any grade occurred in 64 (6%) patients. Overall, 46 (71%) were male and median age was 60 years. Severity of hepatitis was grade 1-2 in 30 patients (47%) (Table 1). The incidence of ≥grade 3 ICIH in the entire cohort was 3.1%. Median time to ICIH diagnosis was 63 days. ICIH occurred alone in 24 patients, and co-occurred with other irAEs in 40 patients. The most common co-occurring irAEs were pneumonitis (n=7); colitis (n=15), thyroid abnormality (n=14); and dermatitis (n=15). ICIH was more common in women (p=0.038), in patients treated with combination ICIs (p<0.001), and among patients receiving first line therapy (p=0.018). Patients who developed ICIH had significantly longer OS than patients who did not develop ICIH; there was no difference in OS between patients with ≥grade 3 ICIH vs grade 1-2 (Table). 33 out of 34 patients with ≥grade3 ICIH were treated with steroids; 3 received mycophenolate and one received infliximab. Of patients with ≥grade 3 ICIH, 11 resumed ICI therapy without recurrent ICIH. Conclusions: Female sex, combination immunotherapy, and line of therapy were associated with ICIH. Patients with ICIH had improved clinical outcomes compared to those that did not develop ICIH, even those with higher grade toxicity. Further study is needed to assist in developing risk stratification models and optimal treatment for ICIH. OS of patients with and without immune checkpoint inhibitor hepatitis.[Table: see text]

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