Management Of Immune-related Adverse Events Research Articles

Considerations for anti-PD1-based first-line treatment of Hodgkin lymphoma.

Anti-PD1-based first-line treatment holds great promise in classical Hodgkin lymphoma. The management of immune-related adverse events in the context of time-limited combined checkpoint blockade and chemotherapy administered in curative intent is a challenge. Kuczmarski and Lynch provide a case-based approach to key toxicities observed in this setting. Commentary on: Kuczmarski etal. Managing common toxicities associated with checkpoint inhibitor and chemotherapy combinations for untreated classic Hodgkin lymphoma. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19478.

Abstract PS14-03: Delayed and post-treatment immune toxicities in patients with breast cancer receiving immune checkpoint inhibitors

Abstract Background: Immune checkpoint inhibitors (ICI) have improved outcomes in patients (pts) with breast cancer, however identification and management of immune-related adverse events (irAE) remains challenging. Delayed irAE have been observed, occurring even after ICI cessation. Prior analyses of delayed irAE have focused on patients with melanoma, lung, and head & neck cancer but data in patients with breast cancer are lacking. Methods: We identified pts with breast cancer who received ICI at our institution between 2012 and 2022 using pharmacy administration records. Charts were reviewed for delayed and post-treatment irAE. Delayed irAE were defined as occurring >90 days after ICI start; post-treatment irAE were defined as occurring >60 days after ICI discontinuation. Events were categorized as irAE if provider notes indicated that the toxicity was related to or possibly related to ICI. Results: 320 consecutive pts with breast cancer (219 metastatic, 96 localized disease) underwent treatment with ICI, of which 79 (25%) developed delayed irAE (40 with metastatic disease, 39 with localized disease). 54 pts had triple negative breast cancer (TNBC), 22 had hormone receptor positive (HR+) disease, and 4 had HER2+ disease. 44 pts received ICI on a clinical trial. The median number of ICI doses was 8, and the median length of follow-up after the first ICI infusion with 29 months. For delayed iRAE, median time to onset was 183 days (range 91-1800 days) with a total of 103 delayed irAE events (see table). 24 pts (7.5%) developed a post-treatment irAE with a total of 27 events. For post-treatment irAE, median time to onset was 112 days after ICI cessation (range 69-1100 days) and median time on ICI was 63 days (range 22-1724 days). 11 of 24 patients who experienced a post-treatment irAE also experienced an irAE while on treatment. Hypothyroidism, colitis, adrenal insufficiency, and hepatitis were the most common irAE at all time points. Rash primarily occurred while still on ICI. All irAE at any time point either self-resolved, resolved with systemic steroids, or continued with indefinite hormone replacement. 45 irAE required systemic steroids, not including hydrocortisone replacement for adrenal insufficiency. There were no grade 4 or 5 irAEs. Conclusions: This is the first evaluation of delayed/post-treatment irAE in a large cohort of patients with breast cancer. 79 pts (25%) experienced delayed irAEs occurring ≥ 90 days after ICI start, with median time to onset of 183 days. 89% of patients with delayed irAE also experienced an irAE at an earlier time point, indicating that early irAE may be a risk for delayed irAE. 24 pts (7.5%) experienced post-treatment irAE with median onset of 121 days after ICI cessation. Diagnosis of delayed irAE requires heightened awareness and prompt treatment. Future work is needed to identify key clinical and molecular markers that predict risk for delayed irAE to better inform treatment & monitoring. Table. Parameter Number of pts (%) Total pts receiving an ICI 320 Delayed irAE 79 (25) >1 delayed irAE 21 (27% of pts with delayed irAE) Patients with delayed irAEs who also had irAE occurring < 90 days after ICI start 70 (89% of pts with delayed irAE) Post-treatment irAE 24 (7.5) Types of delayed irAE (>90 days after ICI start) Any Grade Grade 3 Hypothyroidism 24 (23) 1 (1) Colitis/Diarrhea 19 (18) 3 (3) Rash 14 (14) 0 Adrenal Insufficiency/Hypophysitis 11 (11) 4 (4) Hepatitis 10 (10) 3 (3) Pneumonitis 4 (4) 1 (1) Arthralgia 4 (4) 0 Diabetes mellitus 3 (3) 0 Mucositis 2 (2) 1 (1) Neuropathy 2 (2) 0 Neutropenia 2 (2) 1 (1) Bronchitis 1 (1) 0 Fever 1 (1) 0 Neuromuscular Weakness 1 (1) 0 Autoimmune Hemolytic Anemia 1 (1) 1 (1) Myocarditis 1 (1) 1 (1) Acid Reflux 1 (1) 0 Sarcoidosis 1 (1) 0 Vitiligo 1 (1) 0 Types of post-treatment irAE (>60 days post ICI cessation) Any Grade Grade 3 Hypothyroidism 7 (26) 2 (7) Colitis 7 (26) 3 11) Adrenal Insufficiency/Hypophysitis 6 (22) 1 (4) Hepatitis 4 (15) 3 (11) Arthralgia 1 (4) 0 Neuropathy 1 (4) 0 Neutropenia 1 (4) 1 (4) Rash 1 (4) 0 Citation Format: Saya Jacob, Samantha Fisch, Carolyn Face, Laura Huppert, Zoe Quandt, Laura Quintal, Michelle Melisko, Melanie Majure, Jo Chien, Anne Blaes, Hope Rugo. Delayed and post-treatment immune toxicities in patients with breast cancer receiving immune checkpoint inhibitors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS14-03.

Effect of glucocorticoids for the management of immune-related adverse events on outcome in melanoma patients treated with immunotherapy – a retrospective and biomarker study

Immune-related adverse events (IRAEs) during therapy with immune checkpoint-inhibitors (ICIs) are common, and its management sometimes requires glucocorticoids (GC). Predictors for development of IRAEs and data about the impact of GC on clinical outcome are missing. We evaluated the impact of GC to treat IRAEs on clinical outcome, and plasmatic inflammatory proteins as predictors for IRAEs.Patients with melanoma (n=98) treated with ICIs at Karolinska University Hospital were included. Clinical information and data regarding prescription of systemic GC were collected. Baseline plasma samples (n=57) were analyzed for expression of 92 inflammatory proteins.Forty-four patients developed at least one IRAE requiring systemic GC and the most common was hypocortisolemia (n=11). A median overall survival (mOS) of 72.8 months for patients developing IRAEs requiring GC, 17.7 months for those who did not, and 1.4 months for individuals receiving GC at baseline was observed in Kaplan-Meier curves (p = 0.001). In immortal time bias adjusted analysis patients receiving steroids to treat IRAE survived slightly longer, even though this time trend was not statistically significant. The mOS was 29 months for those treated with GC within 60 days after ICIs start and was not reached for patients receiving GC later. The number of ICIs cycles was higher in subjects receiving GC after 60 days (p=0.0053). Hypocortisolemia occurred mainly in males (10/11) and correlated with favorable outcome. Male patients with hypocortisolemia had lower expression of IL8, TGF-alfa and FGF5 and higher expression of DNER.GC may be used to treat IRAEs without major concern. However, GC early during ICIs may impact clinical outcome negatively. The prognostic value of hypocortisolemia and inflammation proteins as biomarkers should be further investigated.

Impact of immunosuppressive agents on the management of immune-related adverse events of immune checkpoint blockers

BackgroundImmune checkpoint blockers (ICBs) can induce immune-related adverse events (irAEs) whose management is based on expert opinion and may require the prescription of steroids and/or immunosuppressants (ISs). Recent data suggest that these treatments can reduce the effectiveness of ICBs. ObjectiveTo investigate the relationship between the use of steroids and/or ISs and overall survival (OS) and progression-free survival (PFS) among ICB-treated patients with an irAE. MethodsWe prospectively collected data from the medical records of patients with solid tumors or lymphoma in the French REISAMIC cohort and who had been treated with ICBs between June 2014 and June 2020. Results184 ICB-treated patients experienced at least one Common Terminology Criteria for Adverse Events grade ≥ 2 irAE. 107 (58.2%) were treated with steroids alone, 20 (10.9%) with steroids plus IS, 57 (31.0%) not received steroids or IS. The median OS was significantly shorter for patients treated with steroids alone (25.2 months [95% confidence interval (CI): 22.3–32.4] than for patients treated without steroids or IS (63 months [95%CI: 40.4-NA]) and those receiving an IS with steroids (53.4 months [95%CI: 47.3-NA]) (p < 0.001). The median PFS was significantly shorter for patients treated with steroids alone (17.0 months [95%CI: 11.7–22.9]) than for patients treated without steroids or IS (33.9 months [95%CI: 18.0-NA]) and those receiving an IS with steroids (41.1 months [95%CI: 26.2-NA]) (p = 0.006). There were no significant intergroup differences in the hospital admission and infection rates. ConclusionIn a prospective cohort of ICB-treated patients, the use of IS was not associated with worse OS or PFS, contrasting with the use of steroids for the management of irAEs.

Immunotherapy in Cancer Treatment: Harnessing the Power of the Immune System

Immunotherapy has revolutionized cancer treatment by leveraging the body's immune system to fight against cancer cells. This article provides an overview of immunotherapy, focusing on its different modalities, mechanisms of action, clinical applications, and the management of immune-related adverse events. Immune checkpoint inhibitors, such as PD-1 and CTLA-4 inhibitors, are prominent modalities that enhance the immune response by blocking regulatory proteins. Additionally, CAR-T therapy genetically modifies a patient's T cells to target specific proteins on cancer cells, leading to precise cancer cell elimination. Immunotherapy has demonstrated remarkable success in certain malignancies and offers new hope for patients battling cancer.

Narrative review on advancing breast cancer treatment: harnessing the power of PD-1/PD-L1 inhibitors for improved patient outcomes.

Cancer immunotherapy has significantly advanced the field of oncology, providing novel therapeutic strategies for various malignancies, including breast cancer. The programmed cell death protein 1/programmed cell death-ligand 1 (PD-1/PD-L1) pathway is pivotal in immune regulation, and its inhibitors have demonstrated therapeutic benefits in diverse tumors. This review aims to critically examine the role, clinical efficacy, safety, and future directions of PD-1/PD-L1 inhibitors in breast cancer treatment, with a focus on pembrolizumab, nivolumab, and tislelizumab, and to elucidate the challenges and prospects in this dynamic field. A comprehensive literature search was conducted, adhering to Narrative Review reporting checklist for transparent reporting. Data from selected studies were qualitatively analyzed to synthesize key findings related to the mechanisms of action, clinical applications, and challenges of PD-1/PD-L1 inhibitors in breast cancer. PD-1 inhibitors have shown remarkable efficacy in various malignancies, including advanced triple-negative breast cancer (TNBC), where they have been investigated both in combination with chemotherapy and as neoadjuvant/adjuvant treatment. The exploration of these inhibitors in other breast cancer subtypes, such as human epidermal growth factor receptor-positive and hormone receptor-positive breast cancer, is ongoing. The review highlights the challenges in patient selection, management of immune-related adverse events (irAEs), and the emergence of resistance mechanisms. It underscores the need for ongoing research focusing on identifying reliable predictive biomarkers, elucidating mechanisms of resistance, and optimizing treatment strategies. PD-1/PD-L1 inhibitors hold substantial promise in advancing breast cancer treatment. This review provides critical insights and emphasizes the clinical importance of continued scientific exploration to refine patient selection criteria, improve treatment outcomes, and expand the applications of immunotherapy in breast cancer. Further research is imperative to overcome the existing challenges and realize the full therapeutic potential of these inhibitors in breast cancer and other malignancies.

Clinical case of using combination of nivolumab and ipilimumab in first line of treatment for inoperable pleural mesothelioma

Cytostatic therapy still remains the gold standard for the treatment of inoperable pleural mesothelioma with a life expectancy of about 9–18 months. The article presents the results of the use of immune checkpoint inhibitors in the first treatment line for inoperable malignant pleural mesothelioma and management of immune-related adverse events in an elderly patient.

Effects of glucocorticoid use on survival of advanced non-small-cell lung cancer patients treated with immune checkpoint inhibitors.

Lung cancer is the second most common cancer worldwide, with non-small-cell lung cancer (NSCLC) accounting for the majority of cases. Patients with NSCLC have achieved great survival benefits from immunotherapies targeting immune checkpoints. Glucocorticoids (GCs) are frequently used for palliation of cancer-associated symptoms, as supportive care for non-cancer-associated symptoms, and for management of immune-related adverse events (irAEs). The aim of this study was to clarify the safety and prognostic significance of glucocorticoid use in advanced patients with NSCLC treated with immune checkpoint inhibitors (ICIs). The study searched publications from PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine disc, Chinese National Knowledge Infrastructure, Wanfang Data, and Chinese Science and Technology Journal Database up to March 1st, 2022, and conducted a meta-analysis to assess the effects of glucocorticoid use on overall survival (OS) and progression-free survival (PFS) in NSCLC patients treated with ICIs through the available data. The study calculated the pooled hazard ratios (HRs) and 95% confidence intervals (CIs). This study included data from 25 literatures that were mainly retrospective, with 8713 patients included. Patients taking GCs had a higher risk for tumor progression and death compared with those not taking GCs (PFS: HR = 1.57, 95% CI: 1.33-1.86, P <0.001; OS: HR = 1.63, 95% CI: 1.41-1.88, P <0.001). GCs used for cancer-associated symptoms caused an obviously negative effect on both PFS and OS (PFS: HR = 1.74, 95% CI: 1.32-2.29, P <0.001; OS: HR = 1.76, 95% CI: 1.52-2.04, P <0.001). However, GCs used for irAEs management did not negatively affect prognosis (PFS: HR = 0.68, 95% CI: 0.46-1.00, P = 0.050; OS: HR = 0.53, 95% CI: 0.34-0.83, P = 0.005), and GCs used for non-cancer-associated indications had no effect on prognosis (PFS: HR = 0.92, 95%CI: 0.63-1.32, P = 0.640; OS: HR = 0.91, 95% CI: 0.59-1.41, P = 0.680). In advanced NSCLC patients treated with ICIs, the use of GCs for palliation of cancer-associated symptoms may result in a worse PFS and OS, indicating that they increase the risk of tumor progression and death. But, in NSCLC patients treated with ICIs, the use of GCs for the management of irAEs may be safe, and the use of GCs for the treatment of non-cancer-associated symptoms may not affect the ICIs' survival benefits. Therefore, it is necessary to be careful and evaluate indications rationally before administering GCs in individualized clinical management.

Significance of the autoantibody assay in predicting the development of immune-related adverse events in patients receiving atezolizumab plus bevacizumab combination therapy for unresectable hepatocellular carcinoma.

Atezolizumab plus bevacizumab (AB) combination therapy is the first-line treatment for unresectable hepatocellular carcinoma (u-HCC). The management of immune-related adverse events (irAEs) is an important issue associated with achieving a good therapeutic response in patients receiving AB therapy. However, few studies have reported irAE development in patients receiving AB therapy. This study focused on the association between irAE development and autoantibodies at baseline in patients receiving AB therapy. Sixty-one patients receiving AB therapy were enrolled. For autoantibodies, the following antibodies were tested before the start of AB therapy: antinuclear antibodies, rheumatoid factor (RF), anti-thyroglobulin antibodies, thyroid peroxidase antibodies, anti-thyroid stimulating hormone receptor antibodies, and acetylcholine receptor antibodies. A patient was considered to have pre-existing antibodies if any of the listed antibodies were present at baseline. Ten patients (16%) developed irAEs during the observation period. The irAEs included liver injury, hypothyroidism, adrenal insufficiency, adrenocorticotropic hormone deficiency, and rhabdomyolysis. Patients with irAE (n=10) were more likely to be positive for any autoantibody (hazard ratio [HR] 3.7, p=0.047) and RF at baseline (HR 5.4, p=0.035) and to achieve complete response (HR 5.8, p=0.027) than those without. The presence of autoantibodies at baseline was an independent factor associated with irAE development. In the real world, 16% of patients receiving AB therapy for u-HCC developed irAEs. Patients with autoantibodies at baseline are at high risk of developing irAEs and require cautious follow-up.

Relapsing cytokine release syndrome in a patient with metastatic renal cell carcinoma treated with pembrolizumab and axitinib therapy.

As immune checkpoint inhibitors become more widely available, the optimal management of immune-related adverse events (irAEs) is becoming increasingly important. Although irAEs are diverse, reports on cytokine release syndrome are rare. Here, we report a case of a 48-year-old man with relapsing cytokine release syndrome after receiving pembrolizumab and axitinib combination therapy for metastatic renal cell carcinoma. During dose reduction of prednisolone for immune-related hepatitis on day 33 after starting pembrolizumab plus axitinib, the patient suddenly developed abdominal pain, and a few hours later became hypotensive and poorly oxygenated. Despite the use of a ventilator and high doses of catecholamines, blood pressure and oxygenation could not be maintained. Extracorporeal membrane oxygenation and intra-aortic balloon pumping were also administered. The cytokine release syndrome (CRS) was treated with tocilizumab, and his general condition improved. Lower-grade CRS relapsed four times despite a moderate dose of oral prednisolone with mycophenolate mofetil or tacrolimus. After gradual reduction in prednisolone over 5months, the patient was discharged from the hospital. Partial remission of renal cell carcinoma continued for 21months, and salvage radical nephrectomy was performed. The patient remained disease-free without the need for further treatment 9months after surgery.

Identifying the Needs of Health Care Providers in Advanced First-Line Renal Cell Carcinoma: A Mixed-Methods Research.

Systemic treatments for metastatic or unresectable renal cell carcinoma (mRCC) are rapidly evolving. This study aimed at investigating challenges in the care of mRCC to inform future educational interventions for health care providers (HCPs). The sequential mixed-method design consisted of a qualitative phase (semistructured interviews) followed by a quantitative phase (online surveys). Participants included US-based medical oncologists, nephrologists, physician assistants, nurse practitioners, and registered nurses. Interview transcripts were thematically analyzed. Survey data was descriptively and inferentially analyzed. Forty interviews and 265 surveys were completed. Analysis revealed four challenges in the care of mRCC patients. A challenge in staying current with emerging evidence and treatment recommendations was found with 33% of surveyed HCPs reporting suboptimal skills interpreting published evidence on the efficacy and safety of emerging agents. A challenge weighing patient health and preferences in treatment decisions was found, especially among HCPs with 3 to 10 years of practice (37%) who reported suboptimal skills in assessing patients' tolerance to side effects. Promoting a collaborative care approach to the management of immune-related adverse events was a challenge, specifically related to barriers involving nephrologists (eg, diverging treatment goals). Breakdowns in communication were reported (46% of HCPs), especially in the monitoring of side effects and treatment adherence. This study revealed key challenges faced by HCPs when treating and managing patients with mRCC across multiple providers. Future interventions (eg, community of practice) should aim to address the identified gaps and promote a team-based approach to care that strengthens the complementary competencies of HCPs involved.

Development of an eHealth-enhanced model of care for the monitoring and management of immune-related adverse events in patients treated with immune checkpoint inhibitors

PurposeThe use of electronic patient-reported outcome (ePRO) data in routine care has been tied to direct patient benefits such as improved quality of care and symptom control and even overall survival. The modes of action behind such benefits are seldom described in detail. Here, we describe the development of a model of care leveraging ePRO data to monitor and manage symptoms of patients treated with immune checkpoint inhibitors.MethodsDevelopment was split into four stages: (1) identification of an underlying theoretical framework, (2) the selection of an ePRO measure (ePROM), (3) the adaptation of an electronic application to collect ePRO data, and (4) the description of an ePRO-oriented workflow. The model of care is currently evaluated in a bicentric longitudinal randomized controlled phase II trial, the IePRO study.ResultsThe IePRO model of care is grounded in the eHealth Enhanced Chronic Care Model. Patients are prompted to report symptoms using an electronic mobile application. Triage nurses are alerted, review the reported symptoms, and contact patients in case of a new or worsening symptom. Nurses use the UKONS 24-hour telephone triage tool to issue patient management recommendations to the oncology team. Adapted care coordinating procedures facilitate team collaboration and provide patients with timely feedback.ConclusionThis report clarifies how components of care are created and modified to leverage ePRO to enhance care. The model describes a workflow that enables care teams to be proactive and provide patients with timely, multidisciplinary support to manage symptoms.

Prospective Clinical Trials to Advance the Study of Immune Checkpoint Inhibitor Toxicity.

Immune checkpoint inhibitors (ICIs) are a class of drug that produces durable and sustained anti-tumour responses in a wide variety of malignancies. The exponential rise in their use has been mirrored by a rise in immune-related adverse events (IrAEs). Knowledge of such toxicities, as well as effective management algorithms for these toxicities, is essential to optimize clinical efficacy and safety. Currently, the guidelines for management of the IrAEs are based largely on retrospective studies and case series. In this article, we review the current landscape of clinical trials investigating the management of IrAEs with an aim to develop standardised, randomised controlled trial-based management algorithms for ICI-related toxicities.

Selective immune suppression using interleukin-6 receptor inhibitors for management of immune-related adverse events

BackgroundManagement of immune-related adverse events (irAEs) is important as they cause treatment interruption or discontinuation, more often seen with combination immune checkpoint inhibitor (ICI) therapy. Here, we retrospectively evaluated the...

Delayed immune toxicities in patients with breast cancer receiving immune checkpoint inhibitors.

e24091 Background: Immune checkpoint inhibitors (ICI) have improved outcomes in patients with breast cancer, however management of immune-related adverse events (irAE) remains a challenge. Delayed irAE after cessation of ICI have been observed. We sought to characterize delayed irAE occurring at our center. Methods: We identified patients with breast cancer who received ICI at UCSF using ICD codes specific to ICI administration between 2012-2018. After IRB approval, charts were reviewed for delayed irAE. Delayed irAE were defined as occurring &gt;60 days after the last ICI dose; events were counted as irAE if provider notes indicated that the toxicity was/possibly was related to ICI. Data were securely stored using RedCap. Results: We reviewed 100 consecutive patients who underwent ICI (56 metastatic, 44 localized) of which 11 (2 (4%) with metastatic disease, 9 (20.5%) with localized disease) developed delayed irAE. Median age was 42. 3 patients had HR+ disease, 8 patients had triple negative disease. 10 patients received ICI on a clinical trial, including 9 on the neoadjuvant ISPY2 trial. 10 patients received pembrolizumab; 1 received durvalumab. Median number of ICI doses was 4, median follow-up time after last ICI infusion was 46 months. 14 incidences of delayed irAEs were identified (Table). 9 patients experienced both delayed and early irAE. 7 patients experienced 2 irAEs: 1) three dermatitis &amp; delayed hypophysitis/adrenal insufficiency (AI) 2) one AI &amp; delayed thyroiditis 3) one dermatitis and delayed colitis 4) one elevated transaminases &amp; delayed colitis 5) one delayed elevated transaminases and delayed thyroiditis. One patient had 3 irAEs (thyroiditis, delayed AI &amp; delayed arthralgia) and one patient had 4 irAE (colitis, dermatitis, delayed elevated transaminases &amp; delayed neutropenia). Of the 9 patients with &gt; 1 irAE, 3 experienced &gt; 1 delayed irAE (thyroiditis + elevated transaminases; arthralgia + AI; elevated transaminases + neutropenia). All irAE either self-resolved, resolved with systemic steroids or indefinite hormone replacement. 6 irAEs required systemic steroids, not including hydrocortisone replacement for AI. Conclusions: Delayed irAE may occur months after ICI cessation and require awareness for identification. Patients who experience irAE may be more likely to develop additional irAE at either a delayed or earlier time point. Most patients with delayed irAE experienced an irAE at an early time point. Future directions include identifying risk factors for early and delayed irAEs to inform treatment decisions. [Table: see text]

Part II: Interactive case: Drug‐induced endocrine disorders

Part <scp>II</scp>: Interactive case: <scp>Drug‐induced</scp> endocrine disorders

Systematic surveillance of immune-related adverse events in clinical practice and impact of subsequent steroid medication on survival outcomes.

Recent advances in immune-checkpoint inhibitors (ICIs) have highlighted the need for effective management of immune-related adverse events (irAEs). This study aimed to conduct a systematic surveillance of real-world development of irAEs for understanding their characteristics and examine the prognostic impact of steroid use for these events. We retrospectively investigated cancer patients treated with ICIs between 2014 and 2021 and collected information about irAEs throughout their development, management, and clinical outcomes. Overall, 458 patients (45.4%) developed 670 irAEs. The prevalence of irAEs varied by cancer type, but it was increased in regimens with longer treatment durations. Severe irAEs were more common in the nivolumab + ipilimumab and pembrolizumab + axitinib regimens. Patients who received steroids for irAEs at a dosage of < 2mg/kg had comparable prognosis to those who did not receive steroids; however, patients who received methylprednisolone pulse therapy, primarily for severe pneumonitis and hepatitis, had shorter overall survival than those who did not receive steroids (7.8 versus 23.4months, p = 0.016). Furthermore, methylprednisolone pulse therapy for irAEs was a poor prognostic factor in multivariate analysis (hazard ratio: 2.19, 95% confidence interval: 1.34-2.86, p < 0.001). Steroid treatment for irAE does not affect prognosis and should thus be used promptly to control inflammation. However, pulse therapy for severe cases is a poor prognostic factor, and early detection remains the key to managing such irAEs. The irAE characteristics in each regimen should be clarified to establish and provide more sophisticated irAE management, and the current findings will be beneficial to this goal.

Clinical guideline highlights for the hospitalist: Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy.

Management of Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update RELEASE DATE: November 1, 2021 PRIOR VERSION(S): February 14, 2018 DEVELOPER: American Society of Clinical Oncology FUNDING SOURCE: American Society of Clinical Oncology TARGET POPULATION: Adult patients with cancer receiving treatment with immune checkpoint blockade inhibitors alone.

Role-Specific Curricular Needs for Identification and Management of Immune-Related Adverse Events.

Immune checkpoint inhibitors (ICIs) activate the immune system against cancer and have become standard of care for many cancers. With increased ICI use, their toxicitiesknown as immune-related adverse events (irAEs) are becoming more common, but it is unclear how prepared relevant clinicians feel to diagnose and treat irAEs. The objective of this study was to assess irAE knowledge, confidence, and experience among generalists and oncology clinicians to guide future curricular interventions related to irAEs. A 25-item survey with questions assessing knowledge, experience level, confidence, and resource utilization regarding irAE diagnosis and management was sent to University of Chicago-affiliated(UChicago) internal medicine residents and hospitalists (inpatient irAE management)along with UChicago oncology fellows, attendings, nurse practitioners (NPs), andphysician assistants (PAs) (inpatient and outpatient) as well as Chicago community oncologists (outpatient) in June 2022. Overall response rate was 37% (171/467). Knowledge scores averaged below 70% for all clinicians. "No idea" responses were most common with knowledge questions on steroid-sparing agent use and ICI use for patients with preexisting autoimmune disease. IrAE experience correlated with higher knowledge for oncology attendings (p = 0.015) and hematology/oncology NPs/PAs (p = 0.031). IrAE experience correlated with higher confidence for residents (p = 0.026), oncology fellows (p = 0.047), and hematology/oncology NPs/PAs (p = 0.042). Most commonly utilized resources were colleagues and UpToDate, and most clinicians were very likely to use online resources in the future. Knowledge and confidence gaps exist, and they were somewhat mitigated by experience. Future irAE curricula can fill these needs through online role-specific resources: irAE identification for generalists versus irAE identification and management for oncologists.

Current landscape and tailored management of immune-related adverse events.

Unprecedented advances have been made in immune checkpoint inhibitors (ICIs) in the treatment of cancer. However, the overall benefits from ICIs are impaired by the increasing incidence of immune-related adverse events (irAEs). Although several factors and mechanisms have been proposed in the development of irAEs, there is still incomprehensive understanding of irAEs. Therefore, it is urgent to identify certain risk factors and biomarkers that predict the development of irAEs, as well as to understand the underlying mechanisms of these adverse events. Herein, we comprehensively summarize the state-of-the-art knowledge about clinical features and the related risk factors of irAEs. Particularly, we also discuss relevant mechanisms of irAEs and address the mechanism-based strategies, aiming to develop a tailored management approach for irAEs.