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Highlights • Whether antinuclear antibodies (ANA) affect PD-1 inhibitor treatment is unclear. • We examined the safety and efficacy of such treatment in NSCLC patients with ANA. • Immune-related adverse events did not differ between patients with or without ANA. • Progression-free and overall survival were shorter in patients positive for ANA. Abstract Objectives To examine the possible effects of antinuclear antibodies (ANA) on the safety and efficacy of programmed cell death–1 (PD-1) inhibitors in patients with advanced non–small cell lung cancer (NSCLC). Patients and methods Clinical data including ANA status were reviewed retrospectively for patients with advanced NSCLC who received monotherapy with a PD-1 inhibitor. Results Of the 83 patients analyzed, 18 (21.7%) were positive for ANA. The incidence of immune-related adverse events (irAEs) did not differ significantly between patients with ANA (6/18, 33.3%) and those negative for ANA (21/65, 32.3%), although it tended to increase as the ANA titer increased. Progression-free survival (2.9 versus 3.8 months, p = 0.03) and overall survival (11.6 versus 15.8 months, p = 0.03) were significantly shorter in patients positive for ANA than in those without ANA. Conclusion PD-1 inhibitors can be administered safely in advanced NSCLC patients positive for ANA without obvious exacerbation of autoimmune disease, although patients with a high titer of such antibodies may warrant close monitoring. However, the presence of ANA might be associated with a poor outcome of such treatment. [ABSTRACT FROM AUTHOR]

Competing Interests: This work was supported by National Institutes of Health grant 1K08HL16140501; a Sarnoff Scholar Career Development Award; National Institute of General Medical Sciences grant 1RM1 GM131981-02; an American Heart Association Established Investigator Award; the Hoffmann/Schroepfer Foundation; the Additional Venture Foundation; the Joan and Sanford I. Weill Scholar Fund; an iAward grant from Sanofi US; National Heart, Lung, and Blood Institute grant R01HL13483004; and American Heart Association grant AW849785 (Transformative Award). Dr Wu has received funding from Sanofi. Dr Witteles sits on advisory boards for Pfizer, Alnylam, Ionis/Akcea, Eidos, and Intelia. Dr Neal has served in a consulting or an advisory role for AstraZeneca, Genentech/Roche, Exelixis, Jounce Therapeutics, Takeda Pharmaceuticals, Eli Lilly, Calithera Biosciences, Amgen, Iovance, Biotherapeutics, Blueprint Pharmaceuticals, Regeneron Pharmaceuticals, and Natera; and has received research funding from Genentech/Roche, Merck, Novartis, Boehringer Ingelheim, Exelixis, Nektar Therapeutics, Takeda Pharmaceuticals, Adaptimmune, GlaxoSmithKline, Janssen, and AbbVie. Dr Waliany has received consulting fees from AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Immune checkpoint inhibitors (ICIs) are a major class of immuno-oncology therapeutics that have significantly improved the prognosis of various cancers, both in (neo)adjuvant and metastatic settings. Unlike other conventional therapies, ICIs elicit antitumor effects by enhancing host immune systems to eliminate cancer cells. There are 3 approved ICI classes by the U.S. Food and Drug Administration: inhibitors targeting cytotoxic T lymphocyte associated antigen 4, programmed death 1/programmed death-ligand 1, and lymphocyte-activation gene 3, with many more in development. ICIs are commonly associated with distinct toxicities, known as immune-related adverse events, which can arise during treatment or less frequently be of late onset, usually relating to excessive activation of the immune system. Acute cardiovascular immune-related adverse events such as myocarditis are rare; however, data suggesting chronic cardiovascular sequelae are emerging. This review presents the current landscape of ICIs in oncology, with a focus on important aspects relevant to cardiology., Competing Interests: Dr Tan is supported by a postgraduate scholarship from the National Health and Medical Research Council of Australia, a PhD scholarship from the National Heart Foundation of Australia, and an Australian Government Research Training Program Scholarship. Dr Day is a recipient of the Royal Australasian College of Physicians Foundation 2022 Basser Research Entry Scholarship; and has received research support (clinical trials for the institution) from Beigene, Bristol-Myers Squibb, EpimAb, Harbour BioMed, Maxinovel, MSD, Olema Pharmaceuticals, Pfizer, PhamAbcine, and Roche. Dr Nicholls has received research support from AstraZeneca, Amgen, Anthera, CSL Behring, Cerenis, Eli Lilly, Esperion, Resverlogix, Novartis, InfraReDx, and Sanofi-Regeneron; and served as a consultant for Amgen, Akcea, AstraZeneca, Boehringer Ingelheim, CSL Behring, Eli Lilly, Esperion, Kowa, Merck, Takeda, Pfizer, Sanofi-Regeneron, and Novo Nordisk. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Competing Interests: Dr Zhu is supported by the Sarnoff Scholar Career Development Award through the Sarnoff Cardiovascular Research Foundation. Dr Berry has received a speaker honorarium from Merck Pharmaceuticals. Dr Witteles has served on advisory boards for Pfizer, Alnylam, Eidos, Ionis, Intelia, and Janssen. Dr Le has served on advisory boards for Merck, Bristol Myers Squibb, and Janssen; has received research funding from Merck, Bristol Myers Squibb, Aduro Biotech, Curegenix, Medivir, Nouscom, and Abbvie; has received speaking honoraria from Merck; and is an inventor of licensed intellectual property from and managed by Johns Hopkins University. Dr Wu has received research funding from Sanofi; has a patent on induced pluripotent stem cell cardiomyocytes; and has received other expenses from Amgen. Dr Fisher has served on advisory boards for Merck and Genentech and Data Safety Monitoring Boards for Astra Zeneca, Hutchison Pharma and CytomX. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Competing Interests: Dr. Thuny has received congress support from Boehringer Ingelheim and Novartis. Dr. Bonaca is the executive director of CPC, a nonprofit academic research organization affiliated with the University of Colorado, that receives research grant/consulting funding from Abbott, Agios, Alexion Pharma, Alnylam, Amgen, Angionetics, Anthos, ARCA Biopharma, Array, AstraZeneca, Atentiv, Audentes, Bayer, Better Therapeutics, Brigham and Women’s Hospital, Bristol-Myers Squibb, Cardiol Therapeutics, CellResearch, Cook Medical, Cook, CSL Behring, Eidos Therapeutics, EP Trading Co, Esperion Therapeutics, EverlyWell, Faraday, Fortress Biotech, HDL Therapeutics, HeartFlow, Hummingbird Bioscience, Insmed, Janssen, Kowa Research, Lexicon, Merck, Medtronic, Moderna, Novate Medical, NovoNordisk, Pfizer, PhaseBio, PPD Development, Prairie Education and Research, Prothena Ciosciences, Regeneron, Regio Biosciences, Sanifit Therapeutics, Sanofi, Smith and Nephew, Stealth BioTherapeutics, University of Colorado, Worldwide Clinical Trials, Wraser, and Yale Cardiovascular Research Group; holds stock in Medtronic and Pfizer; and has received consulting fees from Audentes. Dr Cautela has received consulting fees from Janssen; lecture fees from Novartis, AstraZeneca, Janssen, and Vifor Pharma; and support for attending meetings from Novartis and AstraZeneca; and has participated on the advisory board or data safety monitoring board for Novartis.

Background: Myocarditis is a dreaded and unpredictable complication of immune checkpoint inhibitors (ICI). We sought to determine whether routinely measured biomarkers could be helpful in monitoring for ICI myocarditis., Objectives: The authors examined biomarker trends of patients on ICI and their association with the incidence of ICI myocarditis and outcomes., Methods: We conducted an observational cohort study of adults who received at least one dose of ICI at Michigan Medicine between June 2014 and December 2021 and underwent systematic serial testing for aspartate aminotransferase (AST) and alanine aminotransferase (ALT), creatine phosphokinase (CPK), and lactate dehydrogenase during ICI therapy., Results: Among 2,606 patients (mean age 64 ± 13 years; 60.7% men), 27 (1.0%) were diagnosed with ICI myocarditis. At diagnosis, patients with myocarditis had an elevated high-sensitivity troponin T (100%), ALT (88.9%), AST (85.2%), CPK (88.9%), and lactate dehydrogenase (92.6%). Findings were confirmed in an independent cohort of 30 patients with biopsy-confirmed ICI myocarditis. A total of 95% of patients with ICI myocarditis had elevations in at least 3 biomarkers compared with 5% of patients without myocarditis. Among the noncardiac biomarkers, only CPK was associated (per 100% increase) with the development of myocarditis (HR: 1.83; 95% CI: 1.59-2.10) and all-cause mortality (HR: 1.10; 95% CI: 1.01-1.20) in multivariable analysis. Elevations in CPK had a sensitivity of 99% and specificity of 23% for identifying myocarditis., Conclusions: ICI myocarditis is associated with changes in AST, ALT, and CPK. An increase in noncardiac biomarkers during ICI treatment, notably CPK, should prompt further evaluation for ICI myocarditis., Competing Interests: Dr Vasbinder is supported by a National Heart, Lung, and Blood Institute funded postdoctoral fellowship (T32HL007853). Dr Hayek is supported by National Heart, Lung, and Blood Institute (R01HL153384) and the National Institute on Diabetes and Digestive and Kidney Diseases (R01-DK128012). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Competing Interests: Dr Jimenez is supported by the National Institutes of Health (R25 HL105400). Dr. Mitchell has received modest consulting from Pfizer and BrigeBio; and research support from Pfizer, Myocardial Solutions, Abbott Laboratories, and Children's Discovery Institute. Dr Campbell is supported by the Amyloidosis Foundation. Dr Lavine is supported by grants from the National Institutes of Health (HL161185, HL150891 and HL151078), the Children’s Discovery Institute (PM-LI-2019-829), the Burroughs Welcome Fund (1014782), and the Leducq Foundation (20CVD02) and by generous gifts through Washington University and Barnes Jewish Hospital. Dr Lavine serves as a consultant for Implicit Biosciences and Medtronic; and is the recipient of sponsored research agreements with Amgen and Novartis; and has a pending patent entitled “Methods for detecting CCR2 receptors” (application number: US17/001,857). Dr Campbell has served on advisory boards for Alnylam Pharmaceuticals and Pfizer Inc; and has received research support from Alnylam Pharmaceuticals, Pfizer Inc, and Akari Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: The use of immune checkpoint inhibitors (ICI) is associated with cardiovascular (CV) events, and patients with pre-existing autoimmune disease are at increased CV risk., Objectives: The aim of this study was to characterize the risk for CV events in patients with pre-existing autoimmune disease post-ICI., Methods: This was a retrospective study of 6,683 patients treated with ICIs within an academic network. Autoimmune disease prior to ICI was confirmed by chart review. Baseline characteristics and risk for CV and non-CV immune-related adverse events were compared with a matched control group (1:1 ratio) of ICI patients without autoimmune disease. Matching was based on age, sex, history of coronary artery disease, history of heart failure, and diabetes mellitus. CV events were a composite of myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke, transient ischemic attack, deep venous thrombosis, pulmonary embolism, or myocarditis. Univariable and multivariable Cox proportional hazards models were used to determine the association between autoimmune disease and CV events., Results: Among 502 patients treated with ICIs, 251 patients with and 251 patients without autoimmune disease were studied. During a median follow-up period of 205 days, there were 45 CV events among patients with autoimmune disease and 22 CV events among control subjects (adjusted HR: 1.77; 95% CI: 1.04-3.03; P  = 0.0364). Of the non-CV immune-related adverse events, there were increased rates of psoriasis (11.2% vs 0.4%; P  < 0.001) and colitis (24.3% vs 16.7%; P  = 0.045) in patients with autoimmune disease., Conclusions: Patients with autoimmune disease have an increased risk for CV and non-CV events post-ICI., Competing Interests: Dr Neilan is supported by gifts from A. Curt Greer and Pamela Kohlberg and from Christina and Paul Kazilionis, the Michael and Kathryn Park Endowed Chair in Cardiology, and a Hassenfeld Scholar Award; and is supported by grants from the National Institute of Health/National Heart, Lung, and Blood Institute (R01HL30539, RO1HL137562, and K24HL150238). Dr Drobni was supported by the ÚNKP-22-4-II-SE New National Excellence Program of the Ministry for Innovation and Technology from the National Research, Development, and Innovation fund. Dr Neilan has been a consultant to and received fees from H3-Biomedicine, Abbvie, Roche, C-4 Therapeutics, Sanofi, CRO Oncology, Genentech, and Amgen, outside of the current work; has received consulting fees from Bristol Myers Squibb for advice focused on myocarditis related to ICIs; and has received grant funding from AstraZeneca and Bristol Myers Squibb. Dr Taron has received funding from Deutsche Forschungsgesellschaft (TA 1438/1-2.T); and is a member of the Speakers Bureaus of Siemens Healthineers and Bayer, unrelated to this work. Dr Hoffmann has received consulting fees from Abbott, Duke University (National Institutes of Health), and Recor Medical, outside the submitted work; and has received research grants from Medimmune, HeartFlow, AstraZeneca, and KOWA. Dr Sullivan has been a consultant to Asana, AstraZeneca, Bristol Myers Squibb, Eisai, Iovance, Merck, Novartis, Pfizer, OncoSec, and Replimune; and has received research funding from Amgen and Merck, all outside the present work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

As the clinical applications of immune checkpoint inhibitors (ICIs) expand, our knowledge of the potential adverse effects of these drugs continues to broaden. Emerging evidence supports the association between ICI therapy with accelerated atherosclerosis and atherosclerotic cardiovascular (CV) events. We discuss the biological plausibility and the clinical evidence supporting an effect of inhibition of these immune checkpoints on atherosclerotic CV disease. Further, we provide a perspective on potential diagnostic and pharmacological strategies to reduce atherosclerotic risk in ICI-treated patients. Our understanding of the pathophysiology of ICI-related atherosclerosis is in its early stages. Further research is needed to identify the mechanisms linking ICI therapy to atherosclerosis, leverage the insight that ICI therapy provides into CV biology, and develop robust approaches to manage the expanding cohort of patients who may be at risk for atherosclerotic CV disease., Competing Interests: Dr Neilan holds the Michael and Kathryn Park Endowed Chair in Cardiology and was also supported, in part, through a kind gift from A. Curtis Greer and Pamela Kohlberg and Christina and Paul Kazilionis, a Hassenfeld Scholar Award, and grants from the National Institutes of Health/National Heart, Lung, and Blood Institute (R01HL130539, R01HL159187, R01HL137562, K24HL150238). Dr Zanni was supported, in part, through grants from the National Institutes of Health/National Heart, Lung, and Blood Institute (R01HL146267 and R01HL137562) and from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (K24AI157882); and has served as the principal investigator on an investigator-initiated research grant from Gilead to her institution (Massachusetts General Hospital). Dr Neilan has served as a consultant for and received fees from Amgen, Genentech, Roche, BMS, Sanofi, CRC Oncology, and AbbVie outside of the current work; and received grant funding from AstraZeneca and Bristol Myers Squibb related to immune checkpoint inhibitors. Dr Suero-Abreu has reported that she has no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

In recent years, the combination of platinum-based chemotherapy and immune checkpoint inhibitors (ICIs) has become the standard treatment for patients with lung cancer. Hepatitis is one of the common toxicities following ICI/chemotherapy. When drug-induced hepatitis occurs, the suspected drug must be discontinued. Since it may be difficult to determine the exact drug causing the hepatitis, liver biopsy may help identify this. We report the case of a patient diagnosed with immune-related adverse event hepatitis from liver biopsy and clinical course. A 45-year-old man with lung adenocarcinoma (stage IV, cT4N3M1c) negative for driver gene mutation was treated with carboplatin (CBDCA), pemetrexed (PEM), and pembrolizumab. Elevated blood aspartate aminotransferase and alanine aminotransferase levels after chemotherapy indicated hepatitis induced by cytotoxic anticancer agents and ICIs. As autoimmune hepatitis was also suspected, liver biopsy was performed and the findings suggested ICI-induced hepatitis. Pembrolizumab was discontinued and CBDCA/PEM was resumed, following which, the primary lesion shrank. When drug-induced hepatitis is suspected, clinicians should actively perform liver biopsy to confirm the diagnosis, so that appropriate therapeutic regimen can be administered., Competing Interests: None., (© 2022 Published by Elsevier Ltd.)

Competing Interests: None disclosed.

Purpose: Intensity-modulated radiotherapy (IMRT) is currently used more commonly than 3-dimensional conformal radiation for definitive thoracic radiation. We examined the efficacy profiles of concurrent chemoradiotherapy (CCRT) with IMRT after durvalumab became clinically available., Methods: We reviewed the clinical records of patients with stage III non-small cell lung cancer (NSCLC) treated with CCRT and IMRT at seven centers in Japan and investigated relapse and survival from May 2018 to December 2019. The primary endpoint of this report was progression-free survival (PFS)., Results: Among 107 patients enrolled in the study, 87 were sequentially administered durvalumab. From CCRT commencement, patients were followed up for a median period of 29.7 months. The median PFS at the end of the CCRT was 20.7 months. Among the 87 patients, 58 experienced disease relapses, of whom 36 (62.1 %) had distant metastases. Multivariate Cox regression analysis revealed that a favorable response to CCRT, a radiation dose ≥ 62 Gy, and stage IIIA NSCLC were associated with prolonged PFS (all P = 0.04). Multivariate logistic regression by landmark analysis revealed that mortality risk factors were durvalumab treatment duration ≤ 11.7 months, a lower maximum grade of immune-related adverse events, FEV 1  < 2805 mL, and radiation dose < 62 Gy (P = 0.01, 0.01, 0.03, and 0.04, respectively)., Conclusions: In patients with NSCLC receiving CCRT using IMRT, long PFS was associated with a better response to CCRT, stage IIIA NSCLC, and an increased radiation dose. The duration of durvalumab consolidation also played an essential role in the survival of patients receiving CCRT with IMRT. (250 words)., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yuichiro Takeda reports grants from Chugai and Boehringer Ingelheim, personal fees from MSD, Ono Pharmaceutical, and Otsuka Pharmaceutical Co. ltd outside the submitted work. Yoko Tsukita reports personal fees from AstraZeneca, Chugai Pharmaceutical, Boehringer Ingelheim, Daiichi Sankyo, and Eli Lilly outside the submitted work. Yukari Uemura reports personal fees from Chugai Pharmaceutical and Lilly outside the submitted work. Eisaku Miyauchi reports grants and personal fees from Chugai pharmaceutical, Lilly, personal fees from Astrazeneca, Taiho pharmaceutical, Daiichi sankyo, Boehringer Ingelheim, Bristol-Meyers Squibb, Novartis, MSD, Kyowa-kirin, Merck Biopharma, Pfizer Inc, Ono Pharmaceutical, Otsuka Pharmaceutical, and Towa Pharmaceutical outside the submitted work. Takaya Yamamoto reports personal fees from AstraZeneca outside the submitted work. Hiroshi Mayahara reports grants from MSD, personal fees from Accuray Japan, AstraZeneca plc, MSD, and Pfizer Inc outside the submitted work. Akito Hata reports grants and personal fees from Eli Lilly, Boehringer Ingelheim and Astrazeneca, personal fees from Chugai, grants from MSD outside the submitted work. Junji Uchida reports personal fees from Astra Zeneca K.K., Chugai pharmaceutical. co.ltd, Bristol Myers Squibb, Taiho Pharma and Boehringer Ingelheim outside the submitted work. Kazuhiro Usui reports personal fees from Astra Zeneca, Chugai, MSD, Pfizer and Boehringer Ingelheim outside the submitted work. Motohiro Tamiya reports personal fees from Chugai Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Taiho Pharmaceutical, Eli Lilly, Novartis, Pfizer, Asahi Kasei Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, MSD, Bayer, Amgen, Kyowa-Kirin, and Nipponkayaku, outside the submitted work. Yuko Oya reports personal fees from AstraZeneca, Chugai pharmaceutical., Taiho Pharmaceutical, Daiichi Sankyo, Eli Lilly, Bristol-Meyers Squibb, and Amgen outside the submitted work. Takeshi Kodaira reports personal fees from Merck Serono Co., Hitachi Co., Bristle Myers Squibb, Accuray Co., Elekta Co., Ono Pharmaceutical Co., AstraZeneca Co., Taiho Pharmaceutical, Chugai Pharmaceutical, and Canon Co. outside the submitted work. Keiichi Jingu reports personal fees from Varina Medical Systems, Inc., Elekta K.K., Shimadzu Medical Systems Corporation, AstraZeneca K.K., Guerbet Japan and grants and personal fees from Eisai, grants from Takeda Pharmaceutical Company Limited, Taiho Phamaceutical, outside the submitted work. Hisatoshi Sugiura reports personal fees from AstraZeneca outside the submitted work. The remaining authors declare no conflict of interest., (© 2022 The Authors.)

The past decade has witnessed a change in landscape of cancer management with the advent of precision oncology. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and have played an important role in improving patient survival. While the patients are living longer, treatment with ICIs are sometimes associated with adverse effects, some of which could be fatal. Radiologists can play a crucial role by early identification of some of these adverse effects during restaging scans. Our paper focuses on the imaging features of commonly occurring ICI toxicities based on organ system., Competing Interests: None., (© 2022 The Authors.)

Competing Interests: None disclosed.

Background: Clinical factors associated with vitiligo in patients receiving anti-programmed cell death-1 (PD-1) remain unknown., Objective: To better characterize the occurrence of vitiligo in patients receiving anti-PD-1., Methods: The present single-center ambispective cohort study included patients with melanoma treated with anti-PD-1. Progression-free survival, overall survival, and objective tumor response were compared between patients with and those without vitiligo using Kaplan-Meier curves and the log-rank test. Demographic and clinical factors associated with vitiligo were evaluated using multivariate logistic regression., Results: Of the 457 patients included in the study, vitiligo developed in 85 patients. The clinical presentation of vitiligo consisted of the presence of ovalar and multiple flecked white macules, mainly located on chronic sun-exposed areas. The presence of vitiligo was associated with a significant improvement in overall survival and progression-free survival ( P  < .001). A Cox proportional hazards model estimation demonstrated markedly improved survival in patients with vitiligo compared with those without vitiligo (aHR [overall survival], 0.20; 95% CI, 0.12-0.33;  P  < .001; and aHR [progression-free survival], 0.33; 95% CI, 0.23-0.47;  P  < .001). In the multivariate logistic regression analyses, men showed an independent increased risk of the development of vitiligo (odds ratio, 1.66). In contrast, the presence of pulmonary metastases was found to be an independent factor associated with a reduced risk of the development of vitiligo (odds ratio, 0.50)., Limitations: Single-center ambispective cohort., Conclusion: Vitiligo in patients receiving anti-PD-1 for advanced melanoma is associated with a better outcome. A gender effect associated with the development of vitiligo will need further investigation., Competing Interests: Dr Dousset received fees from MSD, BMS, Novartis, AbbVie, and Pierre Fabre, outside the submitted work. Dr Kostine received fees from AbbVie, BMS, Lilly, Novartis, and Pfizer, outside the submitted work. Dr Beylot-Barry received fees from MSD, outside the submitted work. Drs Pacaud, Barnetche, Dutriaux, Pham-Ledard, Gérard, Prey, Boniface, and Seneschal and Author Andreu have no conflicts of interest to declare., (© 2021 Published by Elsevier Inc on behalf of the American Academy of Dermatology, Inc.)

Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Ipilimumab and nivolumab combination therapy is effective against unresectable or metastatic renal cell carcinoma. However, it is associated with many immune-related adverse events, including hypophysitis that is difficult to diagnose early because of non-specific initial symptoms. Herein, we report the case of a 54-year-old man with metastatic renal cell carcinoma who developed hypophysitis after receiving ipilimumab and nivolumab combination therapy. The initial symptom was headache. However, endocrine tests showed decreased levels of cortisol, free thyroxine and thyroid-stimulating hormone. Moreover, magnetic resonance imaging revealed pituitary enlargement. Accordingly, we diagnosed hypophysitis and immediately started hydrocortisone replacement therapy, which improved the symptoms., (© 2021 The Authors. Published by Elsevier Inc.)

Ipilimumab plus nivolumab (Ipi/Nivo) has revolutionized advanced renal cell carcinoma (RCC) treatment. However, it encompassed fatal immune-related adverse events (irAEs). Myocarditis with concomitant myasthenia gravis (MG) has a mortality rate of 50%, and a high dose of methylprednisolone (mPSL) should be administered with careful attention to MG exacerbation. We present the case of a 59-year-old man with progressing lung metastasis of RCC. After one cycle of Ipi/Nivo, he experienced myocarditis and MG, managed by mPSL pulse therapy, plasma exchange, and high-dose intravenous immunoglobulin. We share the therapeutic course, aiming to contribute to the limited literature on rare but aggressive irAEs., Competing Interests: None., (© 2020 The Authors. Published by Elsevier Inc.)

As immune checkpoint inhibitor drugs are being used in the treatment of some cancers, unusual adverse events are being reported, labeled as immune-related adverse events. Various endocrinopathies related to immune-related adverse events have been described, among which hypoparathyroidism is exceedingly rare. We report a case of hypoparathyroidism induced by immune checkpoint drugs, highlighting the need for awareness of this emerging complication., (© 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)

In the Checkmate-025 trial, nivolumab treatment prolonged overall survival among patients with previously treated advanced renal cell carcinoma (RCC) compared with treatment with everolimus. Although effective, nivolumab is associated with immune-related adverse events (irAEs). However, the occurrence of hematological irAEs is rare. Some studies have reported on nivolumab-induced thrombocytopenia. Nivolumab associated thrombocytopenia in almost all patients improved with administration of various drugs. However, there have been only a few cases that have reported death owing to cancer aggravation. In this paper, we have described a case of nivolumab-induced thrombocytopenia after third-line treatment for metastatic RCC., Competing Interests: The authors declare no conflict of interest., (© 2020 Published by Elsevier Inc.)