Complications Of Immune Checkpoint Inhibitors Research Articles

Neurologic Complications of Cancer Immunotherapy.

Immunotherapeutic approaches have revolutionized cancer treatment with immune checkpoint inhibitors and adoptive T-cell therapy now approved to treat a variety of solid and hematologic malignancies. This article summarizes the distinctive neurologic side effects of these therapies as well as their management. Neurologic immune-related adverse events are rare but potentially serious complications of immune checkpoint inhibitors. Both peripheral and central nervous system disorders have been described, often necessitating a pause or cessation of immunotherapy. Immune effector cell-associated neurotoxicity syndrome is a potentially serious complication of chimeric antigen receptor T-cell therapy. While symptoms may be mild and self-limited, delirium, encephalopathy, seizures, focal neurologic deficits, and fulminant cerebral edema can be seen. Close neurologic monitoring is imperative. The mainstay of treatment for neurologic complications includes high-dose corticosteroids, although other immunomodulatory strategies may be used in severe or refractory cases. The spectrum of neurologic complications of cancer immunotherapy is broad, encompassing both central and peripheral nervous system disorders, indolent as well as fulminant clinical presentations, and wide-ranging severity with variable response to treatment. Early identification and multidisciplinary management are crucial to balance neurologic recovery and antitumor control.

POSTER: CT-277 Acquired Hemophilia A: An Unusual Complication of Immune Checkpoint Inhibitors

POSTER: CT-277 Acquired Hemophilia A: An Unusual Complication of Immune Checkpoint Inhibitors

CT-277 Acquired Hemophilia A: An Unusual Complication of Immune Checkpoint Inhibitors

CT-277 Acquired Hemophilia A: An Unusual Complication of Immune Checkpoint Inhibitors

Positive direct antiglobulin tests in cancer patients on immune checkpoint inhibitors: A case series from India.

Tumour cells activate immune checkpoints such as programmed death receptor-1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) signalling pathways to inhibit T lymphocyte activation and thus escape from immune surveillance. Immune checkpoint inhibitors (ICPis) reactivate T lymphocytes to recognize cancer cells by blocking CTLA-4 or PD-1. Autoimmune haemolytic anaemia is a rare, but often severe, complication of ICPis. Therefore, we performed a retrospective clinical case review, including serologic, haematology, and biochemistry laboratory results, of three patients who developed autoantibodies to erythrocytes following treatment with pembrolizumab, an anti-PD-1 inhibitor. Serologic testing of blood samples from these patients showed their red cells were positive for direct antiglobulin test (DAT+for IgG in two cases and IgG with C3d in one case). Antibody detection test was negative. No patient had clinical and laboratory features of haemolysis. There were no additional immune-related adverse events. IgG antibodies coating red cells were neither IgG1 nor IgG3 in class and elution was found negative in all. In conclusion, immunohaematology laboratories should be aware of the possibility of erythroid autoantibodies and their nature in cancer patients receiving ICPis. The result of a positive DAT should be interpreted carefully in these patients to exclude other possible causes of anaemia.

Treatment of Refractory Checkpoint-Inhibitor-Induced Hepatitis with Tacrolimus: A Case and Review of the Literature

Immune-related hepatitis (irH) is a fairly frequent complication of immune checkpoint inhibitors (ICIs). Its management is generally based on withholding ICIs and on the rapid initiation of corticosteroids, which is successful in 63 to 96% of cases. Mycofenolate mofetil (MMF) is accepted as a second-line immunosuppressant in the case of the failure of corticosteroids. In rare cases, though, irH is also resistant to MMF and may lead to liver failure. There are no standard third-line treatments and current guidelines are based on a limited number of case reports. We present a case of a metastatic melanoma patient with an immune-related hepatitis refractory to corticosteroids and MMF, that was successfully reversed with tacrolimus. Unfortunately, this was complicated with a serious infection and progressive disease, which illustrates the complexity of treatment of steroid-refractory immunotherapy-related adverse events. Furthermore, we provided a literature review regarding the management of steroid-refractory hepatitis and proposed a strategy to circumvent the current uncertainties in the management of steroid-refractory irH.

#6612 ACUTE KIDNEY INJURY ASSOCIATED WITH IMMUNE CHECKPOINT INHIBITOR THERAPY: REPORT OF 4 CASES

Abstract Background and Aims Immunotherapy using immune check point inhibitors (ICIs) is the cornerstone of modern cancer therapy. Despite significant clinical benefits, ICIs are associated with remarkable adverse events of autoimmune nature involving various organs. Acute Kidney Injury (AKI) occurs more rarely, mainly with the appearance of acute interstitial nephritis. We present a series of patients with AKI after administration of immunotherapy with ICIs. Method Patient 1 with metastatic small cell lung cancer on immunotherapy with atezolizumab presented with purpura on the trunk and lower extremities, AKI, microscopic glomerular hematuria, and proteinuria. Patient 2 with esophageal malignancy on immunotherapy with pembrolizumab and worsening renal function. Patient 3 with endometrial malignancy on immunotherapy with pembrolizumab developed AKI, nephrotic syndrome and microscopic hematuria. Patient 4 with melanoma on immunotherapy with pembrolizumab presented with microscopic hematuria and rash. Results A kidney biopsy was performed in all 4 patients unreavealling the following; Patient 1: pauci-immune necrotizing glomerulonephritis with fibrinoid necrosis and inflammation in the wall of a vessel. Patient 2: acute interstitial nephritis with intense inflammation. Patient 3: findings consistent with focal segmental glomerulosclerosis (FSGS, NOS), without evidence of immune complex disease. Patient 4: focal segmental glomerulosclerosis, moderate interstitial fibrosis and interstitial nephritis in remission. The patient had already been treated with glucocorticoid. In all 4 patients immunotherapy was temporarily discontinued and they were treated with intravenous pulses of methyl-prednisolone followed by oral glucocorticoids, with significant improvement of kidney function and resolution of all extra renal manifestation i.e skin rash etc. Escalation of immunosuppressive therapy with the addition of another agent was avoided in order not to cause relapse of the malignancy. Conclusion AKI is a rare but potentially serious complication of ICIs. Temporal discontinuation of the implicated agent is of major importance while treatment with glucocorticoids may be critical for kindey function. Yet, constant vigilance and sustained collaboration among medical specialists are becoming essential in the increasing use of immunotherapy.

IMMU-19. NIVOLUMAB-INDUCED CNS DEMYELINATION IN A 15-YEAR-OLD WITH CLASSIC HODGKIN LYMPHOMA

Abstract INTRODUCTION Nivolumab associated neurologic immune-related adverse events (irAEs) have been reported in less than 1% of patients and mainly in the adult population. Here we present a pediatric case of nivolumab related CNS demyelination. Case description: 15-year-old male with nodular sclerosis stage III classic Hodgkin lymphoma was enrolled to receive chemotherapy following SWOG S1826 protocol. Eight weeks after the first dose of nivolumab, he had a single episode of seizure. Prolonged EEG showed no epileptiform discharges. Levetiracetam was initiated. Initial MRI showed a non-enhancing T2 hyperintense focal cortical thickening in the left primary motor cortex. CSF studies were significant for mild lymphocytic pleocytosis. One dose of nivolumab was held with subsequent doses given. Levetiracetam was continued and follow-up EEGs were normal. Repeat MRI done three months later showed multiple new parenchymal hyperintense lesions including in the anterior temporal lobe with central curvilinear enhancement, and faintly enhancing lesions in the left fusiform gyrus, juxtacortical white matter of the right middle temporal gyrus, and left superior cerebellar peduncle, findings consistent with CNS demyelination. At this time, CSF showed 9 WBCs (94% lymphocytes) and oligoclonal bands with negative cytology and flow cytometry making CNS lymphoma highly unlikely. The last two doses of nivolumab were held and he was started on methylprednisolone. The most recent MRI ten weeks after the last dose of nivolumab showed resolution of the abnormal findings. DISCUSSION There is limited published literature about neurologic complications of immune checkpoint inhibitors (ICPis) in the pediatric population. CNS demyelination and other neurologic irAEs should be suspected in patients presenting with new neurologic symptoms who started any ICPi within the past three months and after other causes including disease progression, metastasis, metabolic or infectious disorders have been ruled out. Treatment varies depending on severity but includes discontinuation of the ICPi and steroids.

Neurological Complications of Immune Checkpoint Inhibitors (P12-13.004)

<h3>Objective:</h3> To better understand the risks of neurologic toxicities associated with immune checkpoint inhibitors (ICIs). <h3>Background:</h3> Case reports have described various neurological immune-related adverse events (irAEs). There still exists a dearth of data regarding their incidence and prognosis. <h3>Design/Methods:</h3> A single center retrospective study analyzing patients between ages of 18–85 years old from the dates of 3/1/2011 to 9/30/2018 who received immunotherapy for conditions including urothelial cancer, lung cancer, gastric and colorectal cancer, head and neck cancer, lymphoma, melanoma, and renal cell carcinoma. <h3>Results:</h3> Of the 1914 subjects who received immunotherapy, 276 experienced neurotoxicity from multiple causes. Of those 276 subjects, 11 suffered neurological irAEs directly from ICI use. Of the 940 subjects who received pembrolizumab alone, 4 (0.004%) developed neurotoxicity 165 to 575 days from administration. Of the 534 subjects who received nivolumab alone, 3 (0.00956%) developed neurotoxicity 477 days from administration. Of the 594 subjects who received ipilimumab alone, 1 (0.0016%) developed neurotoxicity 27 days from administration. Of the 101 subjects who received nivolumab and ipilimumab, 1 (0.0099%) developed neurotoxicity 65 days from administration. Of the 140 subjects who received pembrolizumab and ipilimumab, 2 (0.014%) developed neurotoxicity 240 to 343 days from administration. Ninety-two subjects received atezolizumab, 7 received avelumab, and 18 received durvalumab; none of these patients experienced neurological irAEs. The neurological irAEs observed were neuropathy (45.45%), acute inflammatory demyelinating polyneuropathy (9.09%), ataxia (9.09%), seizure disorder (18.18%), autoimmune encephalitis (18.18%), receptive aphasia (9.09%) and myopathy (9.09%). Neurological irAEs were treated with steroids, intravenous immunoglobulin, and symptomatic medications like gabapentin, duloxetine, levetiracetam, and thiamine, with about 36% of subjects achieving symptom control. <h3>Conclusions:</h3> Neurological irAEs were extremely rare in our clinical population, but may correlate to the ICI used. We need larger studies to determine the most effective therapy for each neurological irAE and allow oncologists to recognize and treat them expeditiously. <b>Disclosure:</b> Dr. Babu has nothing to disclose. Dr. Sharda has nothing to disclose. Dr. Kolli has nothing to disclose. Dr. Mora-Rodriguez has nothing to disclose. An immediate family member of Dr. Boldig has received personal compensation for serving as an employee of Custom Wire Technologies. An immediate family member of Dr. Boldig has stock in Custom Wire Technologies. Tyra Gatewood has nothing to disclose. Dr. Shah has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Seagen. Dr. Shah has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for EMD Serono. Dr. Shah has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Exelixis. Dr. Swank has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Iovance Pharmaceuticals. Dr. Swank has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for HOPA. Dr. Pina has nothing to disclose. Dr. Peguero has nothing to disclose. Dr. Jaffer has nothing to disclose. Dr. Mokhtari has nothing to disclose. Neha Verma has nothing to disclose.

Immune checkpoint inhibitor-related haemophagocytic lymphohistiocytosis in a patient with non-small cell lung carcinoma.

Hemophagocytic lymphohistiocytosis (HLH) has been reported as a rare complication of immune checkpoint inhibitors (ICI); however, ICI-related HLH is a life-threatening and comparatively late adverse event. Early diagnosis is critical, and it should be included in the differential diagnosis especially in patients with cytopenia with fever and hyperferritinaemia.

T cell dynamism and immune-related adverse events

Immune-related adverse events (irAEs) are a major complication of immune checkpoint inhibitors (ICIs) and occur in an unpredictable fashion. In a Med article, Nunez etal. profile peripheral blood markers in patients treated with ICIs, identifying that dynamic changes in proliferating Tcells and cytokine upregulation are associated with irAEs.

Dearth of ICD Codes for Complications of Immune Checkpoint Inhibitors Impedes Clinical Care and Research.

Immune checkpoint inhibitors (ICIs) are a rapidly expanding class of targeted therapies effective in the treatment of various cancers. However, while efficacious, ICIs have been associated with treatment complications, namely immune-related adverse events (irAEs). IrAEs of the endocrine system are among the most commonly reported irAEs, but despite their high incidence, standardized disease definitions and endocrine IrAE-specific International Classification of Diseases (ICD) codes remain lacking. This dearth of standardized nomenclature and ICD codes has in many ways impeded both the clinical care of patients and the progress of endocrine irAE-related research. ICD codes are used internationally and are essential for medical claims reporting in the health care setting, and they provide a universal language system for recording, reporting, and monitoring diseases. These codes are also a well-accepted form of electronic health record data capture that facilitates the collection, storage, and sharing of data. Therefore, the lack of standardized disease definitions and ICD codes has been associated with misclassification and suboptimal management of individuals with endocrine irAEs and has also been associated with reduced data availability, comparability, and quality. Harmonized and clinically relevant disease definitions along with the subsequent development of endocrine-irAE-specific ICD codes will provide a systematic approach to understanding the spectrum and burden of endocrine irAE diseases, and will have a positive effect across clinical, public health, and research settings.

Biomarker Trends, Incidence, and Outcomes of Immune Checkpoint Inhibitor–Induced Myocarditis

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. The authors examined biomarker trends of patients on ICI and their association with the incidence of ICI myocarditis and outcomes. 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. 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. 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.

Quality and content evaluation of websites with information about immune checkpoint inhibitors: An environmental scan.

BackgroundTrustworthy educational information for patients is critical for increasing their knowledge base and preparing them for shared decision making with clinicians. As the internet has become an important source of health information for many patients, the purpose of this study was to assess the quality and content of websites with educational content about immune checkpoint inhibitors.MethodsWe performed an environmental scan of the currently available websites providing educational information for patients about immune checkpoint inhibitors. We used three search engines: Google, Bing, and Yahoo! (9/20/2021). Two independent investigators selected relevant uniform resource locators (URLs), appraised the quality of the websites, and collected their characteristics. We evaluated the accuracy, completeness, technical elements, design and aesthetics, readability, usability, and accessibility of the websites. The user experience was also evaluated.ResultsWe identified 37 websites for analysis. In 10 websites (27%), it was not possible to know the source of the information provided. Thirty-three (89%) provided a definition with a simple explanation of cancer and treatment and 30 (81%) on complications of immune checkpoint inhibitors; only seven (19%) provided information about the balance between risks and benefits. Thirty-five (95%) provided a statement of purpose. Regarding the design, all 37 (100%) had appropriate visual aspects, typography, and grammar. Thirty-six (97%) were well organized. For most of the websites (n = 35, 95%) the content was easy to find. Only two websites had a readability score of 6, while the others had higher scores. Regarding the user experience, the overall quality of websites was rated as excellent in 16 (43%), good in 14 (38%), and fair in 7 (19%).ConclusionsOur findings reveal that websites with information about immune checkpoint inhibitors mostly have general information about cancer, the treatments, and adverse events. Few websites provide information about the balance between harms and benefits of treatment, costs, the source of the information, or the hierarchy of evidence. These findings identify the gap in the quality and content of websites for patients treated with immune checkpoint inhibitors and can help website creators and developers.

S3482 Small Bowel Enteropathy Induced by Immune Checkpoint Inhibitors: A Case Series

Introduction: While there is a growing understanding of the identification and management of colonic complications of immune checkpoint inhibitors (ICI), less is known about proximal intestinal complications. In this case series, we present 3 patients who developed small bowel enteropathies (SBE) after initiation of ICI. Case Description/Methods: Case 1: A 68-year-old female with stage IV non-small cell lung adenocarcinoma on pembrolizumab developed diarrhea with 7 watery bowel movements daily. EGD was normal and colonoscopy showed minimal sigmoid erythema endoscopically with histologic duodenitis and colitis. Despite treatment with vedolizumab, she remained steroid-dependent. Repeat EGD and sigmoidoscopy showed variable villous abnormality in the duodenum with associated epithelial lymphocytosis, focal active duodenitis, and resolution of colitis. Serologic evaluation revealed hypogammagobulinemia. Nine months after last dose of pembrolizumab, and ultimately therapy with intravenous immunoglobulin therapy and open-capsule budesonide, her symptoms resolved. Case 2: A 42-year-old male with metastatic melanoma treated with ipilimumab and nivolumab developed grade 2 diarrhea with steatorrhea, nausea, vomiting, and unintentional weight loss. EGD was endoscopically normal with biopsies showing active duodenitis with normal colonoscopy. He was initially treated with steroids, but due to persistent symptoms transitioned to infliximab. After receiving 3 doses of infliximab, he had complete resolution of symptoms. Case 3: A 59-year-old female with celiac disease (CD) and metastatic melanoma was started on nivolumab. She developed abdominal pain, early satiety, softer stools, and unintentional weight loss. EGD revealed non-bleeding duodenal erosions and duodenal mucosal changes consistent with celiac disease. Biopsies showed subtotal villous atrophy with increased intraepithelial lymphocytes. CD typing did not suggest refractory sprue. Her presentation was suggestive of a nivolumab-induced exacerbation of CD. After a year of intermittent steroid therapy and adherence to a gluten-free diet, symptoms resolved. Repeat EGD with biopsies showed normal villi and reduced intraepithelial lymphocytes. Discussion: In this case series, we present three patients who developed SBE, highlighting the challenge of its diagnosis and management. SBE should be suspected in individuals with altered stools and no evidence of classic colitis.

Chinese expert consensus on diagnosis and treatment of neurologic immune-related adverse events associated with immune checkpoint inhibitors (2022 edition)

Neurologic immune-related adverse events (NAEs) are rare complications of immune checkpoint inhibitors (ICI). NAEs can affect the central nervous system, peripheral nervous system and neuroendocrine system, they can lead to death and serious dysfunction. NAEs requires standardized diagnosis, treatment and clinicians' high attention. The diagnosis of NAEs is very challenging due to its complexity, diversity and some non-specific clinical manifestations. It needs to be carefully distinguished from neurological dysfunction caused by other diseases such as tumor, infection, metabolism and iatrogenic (non-immune mediated) complications. Therefore, Committee of Neoplastic Supportive-Care of China Anti-Cancer Association and Cancer Clinical Chemotherapy Committee of China Anti-Cancer Association organized experts to conduct literature analysis and evidence level discussion on the clinical key issues related to NAEs, including the epidemiology, pathogenesis, risk factors, general principles of diagnosis and treatment, clinical manifestations and diagnosis and treatment strategies of specific types of NAEs, and the principles of ICI rechallenge after NAEs. Based on the latest clinical evidence and combined with China's clinical practice, the expert committee finally formulated a Chinese expert consensus on diagnosis and treatment of nAEs (2022 edition) for the prevention, diagnosis, comprehensive treatment and follow-up of NAEs.

Mononeuritis multiplex as a rare and severe neurological complication of immune checkpoint inhibitors: a case report

BackgroundMononeuritis multiplex is a rare autoimmune peripheral neuropathy that typically presents in the context of vasculitis, diabetes, infection, or as a paraneoplastic syndrome. Adverse immune-related neurological conditions have been increasingly reported with the use of immune checkpoint inhibitors against cytotoxic T-lymphocyte antigen-4 and/or the programmed cell death protein 1/programmed death ligand-1 axis. Mononeuritis multiplex has only been reported twice from treatment of cancers with immunotherapy.Case presentationHere we report a case of mononeuritis multiplex as a complication of immune checkpoint inhibitor therapy for melanoma. An 80-year-old non-Hispanic white female with recurrent melanoma was treated with combination ipilimumab and nivolumab and subsequently presented with progressive leg weakness, back pain, and difficulty ambulating. The diagnosis of mononeuritis multiplex was made, which was resistant to steroid pulses, chronic steroids, intravenous immunoglobulin, and rituximab. She developed progressive neurologic dysfunction and elected for hospice care. We found only two other cases reported in the literature.ConclusionsIncreased awareness, prompt recognition, and aggressive treatments are likely the best opportunity for improved outcomes in this severe side effect.

Neurologic Complications of Immune Checkpoint Inhibitors

The clinical use of cancer immunotherapy with immune checkpoint inhibitors has transformed the management of cancer and added another effective treatment option for different types of malignancies. The blockade of immune checkpoint pathways triggers an enhanced immune response leading to cancer regression but may also lead to autoimmune toxicities or immune-related adverse events, which may involve skin, endocrine, respiratory, gastrointestinal or neurologic manifestations. Clinically relevant neurologic complications involving the central and/or peripheral nervous system affect up to 1% of patients treated with immune checkpoint inhibitors and may be associated with significant morbidity and mortality. Common neurologic complications include aseptic meningitis and encephalitis, hypophysitis, myasthenia, myositis and neuropathies. Neurologic immune-related adverse events after immune checkpoint inhibition should be distinguished from cancer progression or other complications of cancer therapy (e.g. infections). The treatment of neurologic complications may include holding or withdrawing cancer immunotherapy, anti-inflammatory and immunosuppressive therapies with corticosteroids and steroid-sparing agents, immunomodulation with intravenous immune globulin or plasmapheresis and symptomatic treatment (e.g. antiepileptic medications, pain medications).

Infectious complications of immune checkpoint inhibitors in solid organ malignancies.

BackgroundImmune checkpoint inhibitors (ICIs) are targeted cancer therapies regarded to have less toxicity than chemotherapy. Immune‐related adverse events (irAEs) of ICIs are well described in the literature but limited data exist on their infectious complications. The objective is to describe the spectrum and risk factors for developing serious infections in patients receiving ICIs.MethodsRetrospective review of patients with melanoma, renal cell carcinoma, or nonsmall‐cell lung cancer on nivolumab, pembrolizumab, and/or ipilimumab from January 1, 2017 to November 30, 2017. Exclusion: receipt of less than two ICI doses or history of other malignancy. Characteristics: age, sex, prior chemotherapy, steroid use, and temozolomide or infliximab use. Data identified from microbiology, radiography, serology, or physician note documentation. Serious infection is defined as infections requiring hospitalization and/or IV antibiotics from initiation of ICI until the end of the study period.ResultsOne hundred and eleven pts received ICIs. Suspected or confirmed bacterial infections occurred in 24% (27/111) with 8% (9/111) confirmed bacterial cultures. The overall serious infection rate was 14% (16/111) with 25% (4/16) confirmed bacterial cultures. Suspected or confirmed infection sites: genitourinary 20% (22/111), pneumonia 5% (7/111), skin/soft tissue 7% (8/111). Noninfectious pneumonitis (NIP) occurred in 5% (5/111). No association regarding the risk of infection between the type of malignancy and ICI used. Steroid use was the only risk factor significantly associated with serious infection: 12/16 (75%) on steroids versus 27/95 (28.4%) without steroid use (p = 0.0003).ConclusionThe rate of serious infection with ICI was higher in our study compared with previous reports of pts treated with melanoma. Infectious complications are encountered with ICIs and correlate with steroid use.

79P Immune-related adverse events are correlated with significantly improved outcome in a phase I trial population exposed to combination immunotherapy

Immune-related Adverse Events (IrAE) are a frequent complication of Immune Checkpoint Inhibitors (ICI) and pose a significant diagnostic and therapeutic challenge. In the early phase trial setting, IrAEs are typically underestimated as their time to onset is significantly longer than the conventional time points (usually 3-4 weeks) used to define dose-limiting toxicity (DLT). Individual IrAEs are typically rare; pooling together data from different trials may allow to better characterize the general features of these events; in the phase 1 setting, understanding the true incidence and clinical impact of IrAEs may help better define the patient population best suited for phase 1 trials.

Evaluation and clinical impact of a pharmacist-led, interdisciplinary service focusing on education, monitoring and toxicity management of immune checkpoint inhibitors.

Immune-related adverse events are complications of immune checkpoint inhibitors which require robust patient education and proactive follow-up to ensure timely identification and management. Oncology pharmacist practice models with other anticancer modalities have been well documented, but there is limited evidence assessing the spectrum of pharmacist interventions in patients receiving immune checkpoint inhibitor(s) and the impact of these interventions on patient outcomes. Patients initiated on immune checkpoint inhibitor(s) from 1 January 2016 to 31 August 2019 were included for data collection and analysis. Part 1 featured an intensive pharmacist follow-up cohort (study cohort) and summarized pharmacist interventions. Part 2 compared patient outcomes between the study cohort and a standard of care cohort (control cohort) from a different oncology centre. Patient outcomes included emergency department visits not resulting in admission, hospitalizations due to immune-related adverse event(s), immune checkpoint inhibitor cycles received, treatment discontinuation due to immune-related adverse event(s), completion of finite programmed death-1/death-1 ligand treatment course and completion of ipilimumab. Clinical outcomes were compared using a retrospective, matched cohort design based on age, cancer diagnosis and immune checkpoint inhibitor(s). A total of 143 patients were included in Part 1 encompassing 1664 pharmacist recommendations across 11 categories. The matched cohort yielded 92 matches (n = 184) with a higher odds of immune checkpoint inhibitor discontinuation due to immune-related adverse event(s) in the control cohort (odds ratio (OR) (95% confidence interval (CI)) = 5.5 (1.2-24.8); p = 0.022). Intensive immune-related adverse event education, proactive follow-up and immune-related adverse event management by pharmacists result in clinically meaningful interventions which correlate to improved patient outcomes, namely lower odds of treatment discontinuation due to immune-related adverse event(s).