Strategies for improving the management of immune-related adverse events

With the advent of immunotherapeutic agents, durable and dramatic responses have been observed in several hard-to-treat malignancies, outlining a roadmap to conquering cancer. Immune checkpoint inhibitors (ICPi) are a class of immunotherapeutic agents that attack the tumor cells by reinvigorating the suppressed immune system. However, the unbridled T-cell activity disrupts the immune homeostasis and induces a unique spectrum of side effects called immune-related adverse events (irAEs) in a significant proportion of patients. These irAEs are distinct from the side effects produced by traditional chemotherapeutic agents. Although majority of irAEs are manageable with corticosteroids and other immunosuppressive agents, life-threatening and fatal events have been reported. In the absence of predictive biomarkers to identify patients at risk for irAEs and standardized approach to detect, report, and treat irAEs, management of irAEs has been challenging to the patients, caregivers and the healthcare providers alike. With increasing use of ICPis for treatment of various cancers, the incidence of irAEs will undoubtedly increase. There is a compelling need to develop measures to effectively manage irAEs, both in the community settings and in cancer centers alike. To this end, in this paper, we propose several strategies, such as providing patient education, harmonizing irAE management guidelines, standardizing reporting of irAEs, optimizing the choice of immunosuppressive agents, conducting preclinical, clinical and translational studies to better understand irAEs, including high-risk patients, incorporating diagnostic tools to personalize irAE management using wireless technology and digital health, providing a platform to hear the missing patient’s voice, and sharing evolving data to improve the management of irAEs.

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Side effects of immune-checkpoint inhibitors: Can multiple side effects be seen in a patient?

Journal of Oncology Pharmacy Practice ◽

10.1177/10781552211038136 ◽

2021 ◽

pp. 107815522110381

Author(s):

Esra Özyurt ◽

Serhat Özçelik ◽

Heves Sürmeli ◽

Mehmet Çelik ◽

Murat Ayhan ◽

...

Keyword(s):

T Cells ◽

Cell Death ◽

Side Effects ◽

Programmed Cell Death ◽

Adverse Events ◽

Checkpoint Inhibitors ◽

Host Cells ◽

Immunoglobulin G4 ◽

Programmed Cell Death 1 ◽

Recurrent Renal Cell Carcinoma

Introduction Nivolumab is a human immunoglobulin G4 monoclonal antibody that inhibits programmed cell death-1 activity by binding to the programmed cell death-1 receptors. Cancer cells express increased number of programmed cell death-1 ligands and this allows them to escape the cytotoxic effects of the T cells. Therefore, the negative programmed cell death-1 receptor signal regulates T-cell proliferation and activation is disrupted. However, this change in the activity of the T cells can cause them to lose their ability to recognize host cells. The immune response enabled by these agents has led to side effects, commonly known as “immune-related adverse events.” Case report We report a case of a 66-year-old male patient who was treated with nivolumab for recurrent renal cell carcinoma presented with hepatitis and adrenalitis. Three weeks after starting nivolumab, the patient had abdominal pain and weakness, and then aspartate and alanine transaminase levels were found to be elevated. Management and outcome Hepatitis was predicted to be due to nivolumab, because other causes were excluded. He started using oral methylprednisolone and then, hepatitis improved. However, while receiving methylprednisolone treatment, fludrocortisone was started with the pre-diagnosis of adrenalitis due to the persistence of fatigue, weakness, and hyponatremia and hyperkalemia. With both treatments, the patient's symptoms and sodium and potassium level returned to normal. Discussion This case emphasizes the need for patient's education and awareness of immune-related adverse events, and the importance of understanding the management of life-threatening complications of the checkpoint inhibitors, because these side effects require prompt recognition and treatment.

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Multidisciplinary team management for high grade immune-related adverse events (irAEs): A single center experience.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e15076 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e15076-e15076

Author(s):

PRABHSIMRANJOT SINGH ◽

Osama Abu-Shawer ◽

Amanda Brito ◽

Eric Yenulevich ◽

Shilpa Grover ◽

...

Keyword(s):

Adverse Events ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Massachusetts General Hospital ◽

Average Length ◽

Immunosuppressive Agents ◽

Future Research ◽

Inpatient Service ◽

High Grade

e15076 Background: Immune checkpoint inhibitors (ICIs) are increasingly used in the management of cancer. High grade irAEs are uncommon but can be severe and require hospital admission. There is an urgent need for early identification and triage of patients with irAEs in order to improve their management and outcomes. Methods: We established Immunotherapy toxicity (ITOX) team as the first in nation inpatient service at DFCI and Brigham and Women's Hospital (BWH) along with our partners at Massachusetts General Hospital (MGH) that is specifically devoted to mitigating irAEs. The ITOX service is consistent of 2 PAs and a medical oncology attending with an expertise in immunotherapy. The service utilizes algorithms that are modified from the ASCO and NCCN guidelines by our medical subspecialty experts at BWH. The service uses a multi-disciplinary approach with around the hour consulting service from experts in the field including GI, pulmonary, endocrinology and others. We leveraged EPIC to triage patients who are admitted to BWH and have ever received or currently on immune checkpoint inhibitors (ICIs). The daily list generated by EPIC is then curated manually by a PA to identify patients with potential irAEs. Results: A total of 138 patients with high grade irAEs were admitted to BWH between June 2018 and June 2019. Seventy percent of the 201 irAEs- related admissions were to ITOX service (70% accuracy in triaging). Most common irAEs was colitis (31%), pneumonitis (28%) and hepatitis (13%) which is consistent with the most common reported irAEs due to ICIs. Eighty five percent of the patients had grade 3 irAEs and 15% were admitted with life threatening grade 4 adverse events. About half of the patient had received ICI monotherapy; 33% received combination of ICI and non-ICI (chemotherapy or targeted therapy) and 17% received combination of ICIs. Most patients responded to steroids and only 9% had steroid-refractory irAEs requiring other immunosuppressive agents. The average length of stay for irAEs-related admission was 11 days with readmission rate of 26% within a year. Over 50 patients consented for tissue and blood biospecimen collection at the time of toxicity. Conclusions: We demonstrated the feasibility of empowering EMR to accurately triage patients with suspected irAEs to the ITOX service that is supported by institution developed guidelines and specialists. Our model is adaptable in major academic centers and can have major impact on quality improvement and future research studies that can be conducted in this unique setting.

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Management of immune-related adverse events: A single-center retrospective analysis in a real-world scenario.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e15163 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e15163-e15163

Author(s):

Donatella Iacono ◽

Maria Grazia Vitale ◽

Francesco Cortiula ◽

Marianna Macerelli ◽

Marika Cinausero ◽

...

Keyword(s):

Adverse Events ◽

Checkpoint Inhibitors ◽

Immunosuppressive Agents ◽

Management Strategies ◽

Immunosuppressive Treatment ◽

Second Line ◽

Cutaneous Toxicity ◽

Immune System Activation ◽

Grade 3 ◽

Ecog Ps

e15163 Background: Immune checkpoint inhibitors (ICI), anti CTLA-4 and anti PD-1/PD-L1 agents, have demonstrated an improvement in survival outcome in several malignancies. Therapy with ICI is characterized by immune-related adverse events (irAEs) as a result of exuberant immune system activation. Despite good tolerance for ICI, the potentially severe and life-threatening irAEs underscore the importance of investigating optimal management strategies. Methods: A retrospective series of 130 consecutive patients (pts) treated with ICI from Jan 2012 to Dec 2017 was analyzed. Adverse events with a potential immunological etiology were defined as irAEs and graded according to CTCAE v.4.0. The aim of the study was to evaluate irAEs management in an academic hospital center. Results: Pts with a diagnosis of NSCLC n = 64 (49%), melanoma n = 55 (42%), kidney n = 9 (7%) and others n = 2 (2%) were investigated. Baseline ECOG PS was ≤ 1 in 96% of the pts. ICI represented first line treatment for 27% pts, second line for 57% and third or further line for the remaining 16%. 18% were treated with ipilimumab and 82% with anti PD-1/PD-L1 agents (nivolumab 60%, pembrolizumab 21%, atezolizumab 1%). Overall, 50 (38% of pts) developed an irAE.42% of irAEs were grade 1, 38% grade 2, 14% grade 3 and 6% grade 4. The most frequent irAEs were endocrinopathies in 17 pts (34%), followed by cutaneous toxicity in 9 pts (18%) and colitis and diarrhea in 7 pts (14%). A total of 373 unscheduled accesses were observed, 89 (24%) of them were due to irAEs: 78 were unplanned consultations in the oncology department and 11 in the emergency department. irAEs led to hospitalization in 14 pts for 118 days, cumulatively. Grade ≥ 2 colitis was the most frequent irAE associated with hospitalization, it occurred in 4 pts (29%). Colitis and diarrhea required the longest hospitalization (range 4-31 days). 48% (24 pts) required immunosuppressive treatment. Systemic steroids were the most common immunosuppressive agents used. Only one patient received infliximab as second line immunosuppressive treatment after steroid failure. Totally, irAEs required 67 specialist consultancies and additional diagnostic examinations. 15 pts required ICI discontinuation because of irAEs. Conclusions: In our center prevalence and severity of irAEs were similar to literature data. Considered the complexity of irAEs management, multidisciplinary approach and a trained hospital network plays a key role for a more efficient diagnostic and treatment work-up in pts who received ICI therapy and experienced irAEs.

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Immune-related adverse events associated with immune-checkpoint inhibitors therapy in Mexican patients: Experience at a single center.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e14580 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e14580-e14580

Author(s):

Iván Romarico Romarico Gonzalez Espinoza ◽

Neil Cortés Escobar ◽

Mariana Chiquillo-Domínguez ◽

Gabriela Juárez Salazar ◽

Julio Cesar Garibay Diaz ◽

...

Keyword(s):

Adverse Events ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Malignant Tumors ◽

Checkpoint Inhibitors ◽

Chemotherapeutic Agents ◽

Real World Data ◽

Non Melanoma Skin Cancer ◽

Grade 3 ◽

Patients Experience

e14580 Background: The use of immune-checkpoint inhibitors (ICIs) for solid malignancies is rapidly rising, and many new agents and treatment combinations are in development. However, ICIs have a unique side-effect profile of immune-related adverse events (irAEs) compared with chemotherapeutic agents or targeted therapies. The aim of this work was to describe the irAEs in diverse types of malignant tumors using real-world data. Methods: This is a retrospective and descriptive study of patients with diverse types of advanced malignancies treated with immunotherapy at Centro Oncológico Integral of the Hospital Ángeles in Puebla, México; during the period 2016-2020. Data about the primary neoplasm, ICIs, irAEs, organ system affected, grade and treatment was collected. Clinical and laboratory parameters were obtained by reviewing medical records. Results: A total of 117 patients were included, median age of 65 years, of which 63.2% were male and 36.8% were female. The most frequent neoplasms treated with ICIs were: lung (27.4%), kidney (16.2%), melanoma (12.8%), hepatocellular (9.4%), breast (8.5%), non-melanoma skin cancer (6.0%), mesothelioma (4.3%) and other tumors (15.3%). 39.3% of the patients had no metastases, 41.9% had metastases to at least 1 or 2 sites, and 18.8% to 3 or more sites. The types of ICIs were: nivolumab (35.0%), pembrolizumab (28.2%), atezolizumab (23.9%), ipilimumab + nivolumab (12.0%) and durvalumab (0.9%). The most frequent irAEs were: gastrointestinal (61.5%), neurologic (46.2%), pulmonary (38.5%), metabolic (32.5%) and hematologic (29.1%). 39.3% of the irAEs were reported as grade 1, 31.6% as grade 2, 14.5% as grade 3 and 2.6% as grade 4. Conclusions: Our work shows the incidence of irAEs in a poorly studied population and provides new data that complement that reported by other works, however, further prospective studies are necessary.[Table: see text]

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Real-world safety experience with immune checkpoint inhibitors in Saudi Arabia

Science Progress ◽

10.1177/0036850421997302 ◽

2021 ◽

Vol 104 (1) ◽

pp. 003685042199730

Author(s):

Mohammed Al Nuhait ◽

Eshtyag Bajnaid ◽

Abdulmalik Al Otaibi ◽

Abdullah Al Shammari ◽

Yousef Al Awlah

Keyword(s):

Saudi Arabia ◽

Adverse Events ◽

Emergency Room ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Immunosuppressive Agents ◽

Treatment Discontinuation ◽

Emergency Room Visits ◽

Grade 3

Lay abstract Real-world safety experience with immune checkpoint inhibitors in Saudi Arabia: Immune Checkpoint Inhibitors (ICIs) are rapidly growing and changing cancer care. With introduction of ICIs the landscape for cancer treatment has changed significantly. ICIs are known to induce immune-related adverse effects. This research is intended to shed light on ICIs and describe our safety experience with these agents. This study is a retrospective cohort study aimed to determine the safety of ICIs and its related adverse events at a tertiary hospital in Saudi Arabia. The study was conducted in the oncology center at King Abdulaziz Medical City, Riyadh. We identified study participants by using electronic health care system (BestCare)® to involve patients who received ICIs treatment during the study period from January 2016 up to December 2018, to include a total of 53 patients. Most of our patients were on nivolumab (37 patients) followed by atezolizumab (10 patients), and pembrolizumab (6 patients). The average number of emergency room visits after receiving treatment was three visits per patient. Renal adverse events occurred following ICIs use in nine patients, and none of the reported cases experienced a grade ≥3 event. Moreover, 13 patients experienced a hepatic adverse event, of whom only 1 patient experienced a grade ≥3 event leading to treatment discontinuation. As for diarrhea, among all patients who received ICIs, 14 patients experienced diarrhea, and 5 of them had grade ≥3 events. Also, thyroxine abnormalities occurred in seven patients. While, Pneumonitis occurred in four patients following ICIs use. In addition, we noticed other adverse events with ICIs including (skin reaction, nausea, vomiting, thrombocytopenia, neutropenia, and neurological adverse events). Furthermore, 17 patients required steroids to manage ICIs adverse events. And, no patients in our study required additional management with other immunosuppressive agents. Immunotherapies are rapidly growing and changing cancer care. Immune Checkpoint Inhibitors (ICIs) have the ability to block inhibitory checkpoints and restore the functions of the immune system. ICIs are used for the treatment of several types of cancer, and nowadays, many studies are ongoing in order to get approvals for newer indications. ICIs are known to induce immune-related adverse effects. The safety of ICIs and the most common immune-related adverse events are not yet well recognized for our population since this class of medications is lately introduced in our region, where only limited studies in our population are available in the literature. This research is intended to shed light on ICIs and describe our safety experience with these agents. This study is a retrospective cohort study aimed to determine the safety of ICIs and its related adverse events at a tertiary hospital in Saudi Arabia. The study was conducted in the oncology center at King Abdulaziz Medical City, Riyadh. Study participants were identified by using the electronic health care system (BestCare)® to include patients who were treated with ICIs during the study period from January 2016 up to December 2018. A total of 53 patients were included. Most of our patients were on nivolumab (37 patients) followed by atezolizumab (10 patients), and pembrolizumab (6 patients). The average number of emergency room visits after receiving ICIs was three visits per patient. Renal adverse events occurred following ICIs use in nine patients, and none of the reported cases experienced a grade ≥3 event. Moreover, 13 patients experienced a hepatic adverse event, of whom only 1 patient experienced a grade ≥3 event leading to treatment discontinuation. As for diarrhea, among all patients who received ICIs, 14 patients experienced diarrhea, and 5 of them had grade ≥3 events. Also, thyroxine abnormalities occurred in seven patients. While, pneumonitis occurred in four patients following ICIs use. In addition, we noticed other adverse events with ICIs, including (skin reaction, nausea, vomiting, thrombocytopenia, neutropenia, and neurological adverse events). Furthermore, 17 patients required steroids to manage ICIs adverse events. And, no patients in our study required additional management with other immunosuppressive agents. Patients treated with immune checkpoint inhibitors could have a variety of adverse drug events that might lead to treatment discontinuation and increase overall emergency room visits. This study highlights the most common adverse drug events associated with ICIs use at a tertiary care center in Saudi Arabia.

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Intestinal Microbiome Associated With Immune-Related Adverse Events for Patients Treated With Anti-PD-1 Inhibitors, a Real-World Study

Frontiers in Immunology ◽

10.3389/fimmu.2021.756872 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wenhui Liu ◽

Fang Ma ◽

Bao Sun ◽

Yiping Liu ◽

Haoneng Tang ◽

...

Keyword(s):

Adverse Events ◽

Checkpoint Inhibitors ◽

Predictive Biomarkers ◽

Intestinal Bacteria ◽

Classification Model ◽

Intestinal Microbiome ◽

Fecal Samples ◽

Microbial Biomarkers ◽

Advanced Malignancies ◽

Auc Value

AimImmune checkpoint inhibitors (ICIs) have updated the treatment landscape for patients with advanced malignancies, while their clinical prospect was hindered by severe immune-related adverse events (irAEs). The aim of this study was to research the association between gut microbiome diversity and the occurrence of ICI-induced irAEs.Patients and MethodWe prospectively obtained the baseline fecal samples and clinical data from patients treated with anti-PD-1 inhibitors as monotherapy or in combination with chemotherapy or antiangiogenesis regardless of treatment lines. The 16S rRNA V3-V4 sequencing was used to test the gene amplicons of fecal samples. The development of irAEs was evaluated and monitored from the beginning of therapy based on CTCAE V5.01.ResultsA total of 150 patients were included in the study and followed up for at least 6 months. A total of 90 (60%) patients developed at least one type of adverse effect, among which mild irAEs (grades 1–2) occurred in 65 patients (72.22%) and severe irAEs (grades 3–5) in 25 patients (27.78%). Patients with severe irAEs showed a visible higher abundance of Streptococcus, Paecalibacterium, and Stenotrophomonas, and patients with mild irAEs had a higher abundance of Faecalibacterium and unidentified_Lachnospiraceae. With the aid of a classification model constructed with 5 microbial biomarkers, patients without irAEs were successfully distinguished from those with severe irAEs (AUC value was 0.66).ConclusionCertain intestinal bacteria can effectively distinguish patients without irAEs from patients with severe irAEs and provide evidence of gut microbiota as an informative source for developing predictive biomarkers to predict the occurrence of irAEs.

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Management of adverse events in cancer treatment with immune checkpoint inhibitors

Journal of Korean Medical Association ◽

10.5124/jkma.2021.64.5.358 ◽

2021 ◽

Vol 64 (5) ◽

pp. 358-365

Author(s):

Myoung Joo Kang

Keyword(s):

Adverse Events ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Organ Transplant ◽

Chemotherapeutic Agents ◽

Careful Consideration ◽

The Body ◽

Close Monitoring ◽

Multiple Organs

The use of immune checkpoint inhibitors is associated with a spectrum of immune-related adverse events related to the mechanism of action which is quite different from that of cytotoxic chemotherapy. Adverse effects can affect multiple organs of the body and are most common in the skin, gastrointestinal tract, lungs, and endocrine tissues, including the thyroid, adrenal gland, pituitary gland, as well as musculoskeletal, renal, nervous, hematologic, cardiovascular, and ocular systems. Any changes should be considered as being related to treatment with immune checkpoint inhibitors. Adverse events are very infrequent, but may be very serious and, even lethal, such as neurological disorders and myocarditis. When compared with standard chemotherapeutic agents, programmed death 1/programmed deathligand 1inhibitors are associated with a lower incidence of bone marrow suppression, anorexia, nausea, vomiting, and diarrhea. Immune checkpoint inhibitor therapy can usually continue in the presence of mild immune-related adverse events with close monitoring. However, moderate to severe immune-related adverse events may be associated with a severe decline in organ function and quality of life, and may result in fatal outcomes. Hence, these toxicities require early detection and proper management. The management of immune-related adverse events usually involves corticosteroid therapy or the use of immunomodulators. The use of immune checkpoint inhibitors in patients with preexisting autoimmune disease or a history of prior organ transplant should include careful consideration and a robust discussion of potential risks and benefits.

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Immunological and clinical profiles of patients with advanced or metastatic melanoma receiving immune checkpoint inhibitors to investigate potential biomarkers for immune-related adverse events.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e14037 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e14037-e14037

Author(s):

Stephanie A. Berg ◽

Michael Wesolowski ◽

Brianna Burke ◽

Courtney Regan Wagner ◽

Joseph I Clark ◽

...

Keyword(s):

T Cells ◽

Adverse Events ◽

Cd8 T Cells ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Molecular Mechanisms ◽

Checkpoint Inhibitors ◽

Rank Correlation ◽

Predictive Biomarkers ◽

Biological Variables

e14037 Background: Immune-related adverse events (irAEs) related to immune checkpoint inhibitors (ICIs) may target any organ and originate from autoreactive T cells injuring host tissues. There is a need to develop prognostic and predictive biomarkers to distinguish patients (pts) who will benefit from ICIs avoiding irAEs during treatment. We propose that irAEs are the result of many biological variables. We hypothesize that within each pts complex immunological profile, there may be patterns and associations which exist that represent a state of inflammation that is present prior to ICI therapy and hypothesize this could predict irAEs development. Methods: We created individual immunological profiles of 11 pts diagnosed with MM prior to receiving ICIs. Assays included: PBMC composition, circulating chemokines/cytokines, and IκB degradation status. CD4 and CD8 T cells were studied for their phenotype, activation status, proliferative capacity and cytolytic granules. Clinical data was collected on a larger MM pt cohort (n = 41) and descriptive statistics were utilized to characterize reported irAEs . Results: 110 input markers were utilized for immune signature analysis. 6 of the 11 pts reported grade 2+ irAEs after ICI therapy. The pro-inflammatory CCL13, CCL1, FLT-3, IL12p40, TRAIL, and granzyme b expressing CD4 T cells at steady state and after CD3 activation were significantly higher in pts with irAEs. Known inflammatory suspects (i.e., IL-2, IL-15, TNF-a or % CD8 T cells) were not associated with irAE development . A rank correlation test showed significant associations between the levels of these factors. irAEs were reported in 41% (n = 17) for our larger cohort, most frequently skin rash (7%), colitis (7%), hepatitis (7%) and thyroid dysfunction (4%). Conclusions: The immune signatures of pts with irAEs are highly heterogeneous and possess distinctive immunological patterns. Our results introduce possible molecular mechanisms that may aid understanding of irAE development, perhaps providing the basis for a new model prospectively testing these markers to risk stratify pts receiving ICIs.

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Novel platform leveraging electronic medical record (EMR) to triage patients admitted with high-grade immune-related adverse events (irAEs) to the immune-toxicity (ITOX) service

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-000992 ◽

2020 ◽

Vol 8 (2) ◽

pp. e000992

Author(s):

Osama Abu-Shawer ◽

Prabhsimranjot Singh ◽

Eric Yenulevich ◽

Amanda Brito ◽

Jian Ni ◽

...

Keyword(s):

Adverse Events ◽

Medical Record ◽

Electronic Medical Record ◽

Checkpoint Inhibitors ◽

Average Length ◽

Immunosuppressive Agents ◽

Rapid Expansion ◽

High Grade ◽

Average Length Of Stay ◽

Immune Toxicity

BackgroundThe incidence of high-grade immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICIs) is increasing due to the rapid expansion of indications for their use. There is an urgent need for a feasible approach of identifying patients with high-grade irAEs to ensure early detection and proper management of this unique set of toxicities.MethodsWe established one of the first inpatient services that are specifically devoted to mitigating irAEs. The service uses a multidisciplinary approach with consulting service from experts in managing irAEs. We are leveraging the electronic medical record (EMR) to triage patients who are admitted to the hospital and have received or are currently receiving ICIs. A list of patients with ICI exposure is generated daily by EMR and then curated manually to identify patients with potential irAEs.ResultsA total of 129 patients with high-grade irAEs were admitted between June 2018 and June 2019. The most common irAEs were colitis (32%), pneumonitis (30%), and hepatitis (14%). Eighty five per cent of the patients had grade 3 irAEs and 15% had grade 4–5. About half of the patients had received ICI monotherapy; 30% had received combination of ICIs and non-ICIs; and 19% had received a combination of ICIs. Only 9% of patients had steroid-refractory irAEs requiring other immunosuppressive agents. The average length of stay for irAE-related admission was 11 days with a readmission rate due to recurrent irAEs of 26% within a year.ConclusionWe demonstrated the feasibility of using the EMR to accurately triage patients with suspected irAEs to a dedicated immune-toxicity service. Our model is adaptable in major academic centers and could have a major impact on quality of care and future clinical research addressing irAEs.

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Toxicities associated with checkpoint inhibitors—an overview

Rheumatology ◽

10.1093/rheumatology/kez418 ◽

2019 ◽

Vol 58 (Supplement_7) ◽

pp. vii7-vii16 ◽

Cited By ~ 9

Author(s):

Laura Spiers ◽

Nicholas Coupe ◽

Miranda Payne

Keyword(s):

Immune System ◽

Side Effects ◽

Adjuvant Therapy ◽

Adverse Events ◽

Side Effect ◽

Checkpoint Inhibitors ◽

Side Effect Profile ◽

Diagnostic Strategies ◽

Organ Specific ◽

Autoimmune Conditions

Abstract Immunotherapy has an increasing role in the management of cancer, both in metastatic disease and as an adjuvant therapy. However, sensitization of the immune system with checkpoint inhibitors comes with a unique side effect profile. Full appreciation of this can take some time to emerge as some adverse events are rare, or can be subtle and potentially overlooked. Clinician awareness of these side effects can be particularly important in patients with pre-existing autoimmune conditions. Here we describe common symptoms and diagnostic strategies for organ-specific side effects of anti-CTLA-4 and anti-PD-1/PD-L1 immunotherapy agents.

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