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Introduction: Cholangiocarcinomas (CCA) are rare, aggressive tumors often diagnosed in advanced stages with limited evidence guiding therapy on progression. Case Report: We report a case of advanced CCA with rapid and aberrant progression, refractory to multiple lines of therapy, that resulted in severe hepatic dysfunction secondary to tumor burden with a BRAF V600E mutation and high tumor proportion score (TPS) of 99%. To our knowledge, this is the first reported use of BRAF/MEK inhibition to target BRAF V600E in a patient with severe hepatic dysfunction leading to rapid normalization of the patient’s liver dysfunction within days. No adverse events were recorded during either initial titration or maintenance periods. Programmed death-1 (PD-1) inhibitor was added to BRAF/MEK inhibition, and the patient continues to have clinical therapeutic response. Conclusion: This case highlights the use of BRAF/MEK inhibition in CCA with BRAF V600E mutations in hepatic dysfunction due to tumor burden and the role of combining immune checkpoint inhibitors.

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PURPOSE The risk of immune checkpoint inhibitor therapy–related GI adverse events in patients with cancer and inflammatory bowel disease (IBD) has not been well described. We characterized GI adverse events in patients with underlying IBD who received immune checkpoint inhibitors. PATIENTS AND METHODS We performed a multicenter, retrospective study of patients with documented IBD who received immune checkpoint inhibitor therapy between January 2010 and February 2019. Backward selection and multivariate logistic regression were conducted to assess risk of GI adverse events. RESULTS Of the 102 included patients, 17 received therapy targeting cytotoxic T-lymphocyte antigen-4, and 85 received monotherapy targeting programmed cell death 1 or its ligand. Half of the patients had Crohn’s disease, and half had ulcerative colitis. The median time from last active IBD episode to immunotherapy initiation was 5 years (interquartile range, 3-12 years). Forty-three patients were not receiving treatment of IBD. GI adverse events occurred in 42 patients (41%) after a median of 62 days (interquartile range, 33-123 days), a rate higher than that among similar patients without underlying IBD who were treated at centers participating in the study (11%; P < .001). GI events among patients with IBD included grade 3 or 4 diarrhea in 21 patients (21%). Four patients experienced colonic perforation, 2 of whom required surgery. No GI adverse event–related deaths were recorded. Anti–cytotoxic T-lymphocyte antigen-4 therapy was associated with increased risk of GI adverse events on univariable but not multivariable analysis (odds ratio, 3.19; 95% CI, 1.8 to 9.48; P = .037; and odds ratio, 4.72; 95% CI, 0.95 to 23.53; P = .058, respectively). CONCLUSION Preexisting IBD increases the risk of severe GI adverse events in patients treated with immune checkpoint inhibitors.

PURPOSE: Immune checkpoint inhibitors (ICIs) cause immune-related adverse events (irAEs). The proportion of patients who are hospitalized for irAEs and their spectrum, management, and outcomes are not well described. METHODS: We report the proportion of hospitalized patients in an academic center who were treated with ICIs from May to December 2017. Patient characteristics, toxicities, management, and outcomes for confirmed irAE admissions are reported. Associations between patient features and irAE hospitalizations are examined. RESULTS: Twenty-three percent (n = 100) of 443 patients who were admitted to an academic oncology center over 6 months had ever received ICIs. Of these patients, 41% were admitted for suspected irAEs and 23% were confirmed irAEs. IrAEs accounted for 5% of all oncology hospitalizations (n = 23). Ninety-one percent of patients with confirmed irAEs prompted a medicine subspecialist consultation, most commonly gastroenterology (22%). Fifteen patients (65%) had their irAEs improve/resolve, seven (30%) had worsening irAEs, and three (13%) died of their irAEs. The majority of patients (n = 20; 87%) discontinued ICIs after discharge. Among ICI-treated patients who required admission, an increased likelihood of irAE-related hospitalization was associated with patient age older than 65 years (odds ratio, 5.4; 95% CI, 1.6 to 17.8) and receipt of combination immunotherapy (OR, 6.8; 95% CI, 2.0 to 23.2). CONCLUSION: A notable proportion of ICI-treated patients are hospitalized for irAEs, and these patients have a high demand for multidisciplinary management. Older age and combination ICI treatment were associated with an increased risk of irAE-related hospitalization. Whereas these data are from an academic center and include patients in clinical trials, with expanding use of ICIs, these data have important implications for inpatient service planning and risk stratification.

Methadone use for opioid use disorder and chronic pain has increased since the start of the century with about 4.4 million dispensed prescriptions in 2009. With increased use of methadone, there has been increasing reporting of less commonly reported side effects (ie, hypoglycaemia). Here, we describe a woman in her 70s with history of opioid use disorder on methadone, stage 4 chronic kidney disease and prior hypoglycaemic episodes who initially presented with perforated gastric ulcer requiring surgical repair. Her perioperative course was complicated by profound hyperinsulinaemic hypoglycaemia. Given concern for methadone-induced hypoglycaemia, methadone was discontinued with monitoring of subsequent blood glucose, insulin, C peptide, proinsulin, β-hydroxybutyrate and blood methadone levels. As the serum methadone levels decreased, insulin levels substantially decreased in parallel. After 21 days off methadone, dextrose infusion was discontinued with restoration of euglycaemia. In a patient with hyperinsulinaemic hypoglycaemia and methadone use, it is important to consider discontinuing methadone and re-evaluate fasting glucose levels prior to an extensive and invasive insulinoma workup.

With expanding use of immune-checkpoint inhibitors (ICIs), the incidence of immune-related adverse events (irAEs) is increasing, posing a new clinical challenge for practitioners. The spectrum and incidence of irAEs differ by the immune checkpoint molecule that is blocked, such that CTLA-4 inhibitors are associated with colitis and hypophysitis, while PD-1/PD-L1 inhibitors with pneumonitis and thyroiditis. However, despite ICI type, irAEs can affect every organ system in the body. Improved irAE outcomes are related to their timely recognition and management. This chapter explores what is known about the epidemiology, risk factors, diagnosis, management, and outcomes of non-rheumatic irAEs. In addition, we include an examination of late-breaking research into the prevention and management of irAEs.

BACKGROUND The COVID-19 pandemic has brought about sweeping change in health care delivery, which has shifted from in-person consultations to a web-based format. Few medical schools provide web-based medicine or telemedicine training to their learners, though this is likely to be important for future medical practice. OBJECTIVE This tutorial communicates a framework for incorporating medical students into primary care telemedicine clinics. METHODS A third-year medical student and internal medicine attending physician from the Johns Hopkins University completed telemedicine clinic visits in April 2020 by using a variety of video platforms and via telephone calls. RESULTS Nine telemedicine visits were completed over 4 clinic days. Our patients were, on average, aged 68 years. The majority of patients were female (6/9, 67%), and most appointments were completed via a video platform (6/9, 67%). Additionally, our experience is summarized and describe (1) practical tips for how to prepare for a telehealth visit; (2) technology considerations; (3) recommendations for participation during a telehealth visit; (4) debriefing and feedback; (5) challenges to care; and (6) student, care provider, and patient reactions to telemedicine visits. CONCLUSIONS Telemedicine clinics have been successfully used for managing patients with chronic conditions, those who have attended low-risk urgent care visits, and those with mental health concerns. Patients have reported high patient satisfaction scores for telemedicine visits, and the majority of patients are comfortable with having medical students as part of their care team. Moving forward, telemedicine will remain a popular method for receiving health care. This study has highlighted that medical students can successfully be integrated into telemedicine clinics and that they should be exposed to telehealth whenever possible prior to residency.

Background The COVID-19 pandemic has brought about sweeping change in health care delivery, which has shifted from in-person consultations to a web-based format. Few medical schools provide web-based medicine or telemedicine training to their learners, though this is likely to be important for future medical practice. Objective This tutorial communicates a framework for incorporating medical students into primary care telemedicine clinics. Methods A third-year medical student and internal medicine attending physician from the Johns Hopkins University completed telemedicine clinic visits in April 2020 by using a variety of video platforms and via telephone calls. Results Nine telemedicine visits were completed over 4 clinic days. Our patients were, on average, aged 68 years. The majority of patients were female (6/9, 67%), and most appointments were completed via a video platform (6/9, 67%). Additionally, our experience is summarized and describe (1) practical tips for how to prepare for a telehealth visit; (2) technology considerations; (3) recommendations for participation during a telehealth visit; (4) debriefing and feedback; (5) challenges to care; and (6) student, care provider, and patient reactions to telemedicine visits. Conclusions Telemedicine clinics have been successfully used for managing patients with chronic conditions, those who have attended low-risk urgent care visits, and those with mental health concerns. Patients have reported high patient satisfaction scores for telemedicine visits, and the majority of patients are comfortable with having medical students as part of their care team. Moving forward, telemedicine will remain a popular method for receiving health care. This study has highlighted that medical students can successfully be integrated into telemedicine clinics and that they should be exposed to telehealth whenever possible prior to residency.

BackgroundImmune-checkpoint inhibitor (ICI)-pneumonitis that does not improve or resolve with corticosteroids and requires additional immunosuppression is termed steroid-refractory ICI-pneumonitis. Herein, we report the clinical features, management and outcomes for patients treated with intravenous immunoglobulin (IVIG), infliximab, or the combination of IVIG and infliximab for steroid-refractory ICI-pneumonitis.MethodsPatients with steroid-refractory ICI-pneumonitis were identified between January 2011 and January 2020 at a tertiary academic center. ICI-pneumonitis was defined as clinical or radiographic lung inflammation without an alternative diagnosis, confirmed by a multidisciplinary team. Steroid-refractory ICI-pneumonitis was defined as lack of clinical improvement after high-dose corticosteroids for 48 hours, necessitating additional immunosuppression. Serial clinical, radiologic (CT imaging), and functional features (level-of-care, oxygen requirement) were collected preadditional and postadditional immunosuppression.ResultsOf 65 patients with ICI-pneumonitis, 18.5% (12/65) had steroid-refractory ICI-pneumonitis. Mean age at diagnosis of ICI-pneumonitis was 66.8 years (range: 35–85), 50% patients were male, and the majority had lung carcinoma (75%). Steroid-refractory ICI-pneumonitis occurred after a mean of 5 ICI doses from PD-(L)1 start (range: 3–12 doses). The most common radiologic pattern was diffuse alveolar damage (DAD: 50%, 6/12). After corticosteroid failure, patients were treated with: IVIG (n=7), infliximab (n=2), or combination IVIG and infliximab (n=3); 11/12 (91.7%) required ICU-level care and 8/12 (75%) died of steroid-refractory ICI-pneumonitis or infectious complications (IVIG alone=3/7, 42.9%; infliximab alone=2/2, 100%; IVIG + infliximab=3/3, 100%). All five patients treated with infliximab (5/5; 100%) died from steroid-refractory ICI-pneumonitis or infectious complications. Mechanical ventilation was required in 53% of patients treated with infliximab alone, 80% of those treated with IVIG + infliximab, and 25.5% of those treated with IVIG alone.ConclusionsSteroid-refractory ICI-pneumonitis constituted 18.5% of referrals for multidisciplinary irAE care. Steroid-refractory ICI-pnuemonitis occurred early in patients’ treatment courses, and most commonly exhibited a DAD radiographic pattern. Patients treated with IVIG alone demonstrated an improvement in both level-of-care and oxygenation requirements and had fewer fatalities (43%) from steroid-refractory ICI-pneumonitis when compared to treatment with infliximab (100% mortality).

OBJECTIVES/GOALS: This study aims to assess the outcomes of a new virtual multidisciplinary immune-related toxicity (IR-tox) team implemented at Johns Hopkins Hospital. In particular, to understand if the IR-tox team’s input reduced the number of inpatient hospitalizations for irAEs for referred patients. METHODS/STUDY POPULATION: Since August 2017, nearly 250 patient referrals to the IR-tox team have been created and stored in an electronic database. Through retrospective chart review, hospitalization and irAE management data will be collected for these patients to assess whether rates for suspected irAEs have decreased. These rates will be compared against historical controls. We will assess the features of hospitalized patients, their immunotherapy regimens, and management to identify high-risk groups who may require early intervention. Additionally, we aim to understand what patient features are associated with IR-Tox team referral and subsequent hospitalization. RESULTS/ANTICIPATED RESULTS: The IR-tox team provided a new multidisciplinary channel to help physicians diagnose and manage complex irAEs. The goal of the team was the reduce the number of irAE-related hospitalizations as, historically, 85% of high-grade irAEs have required hospitalization. A clinically meaningful reduction is defined as lowering the hospitalization rate to 75%. Planned analyses includes calculating the hospitalization rate, using descriptive statistics to summarize patient features, multivariate analyses to understand features associated with both IR-Tox team referral and hospitalization, and computing the relative risk reduction to assess the efficacy of subspecialist referral implementation. DISCUSSION/SIGNIFICANCE OF IMPACT: IrAEs are challenging to diagnose and treat. They contribute to a notable proportion of hospitalizations in those treated with immunotherapy. With expanding use of immunotherapy, widespread implementations of IR-Tox teams may help reduce hospitalizations and costs associated with care for irAEs.

e15074 Background: Immune checkpoint inhibitors (ICIs) cause immune-related adverse events (irAEs) that may require multidisciplinary input. We developed an IR-Tox program consisting of an electronic irAE referral platform +/- in-person consultation, and a monthly irAE tumor board, run by an IR-Tox team comprising 38 organ-specialists and oncologists. Herein, we present our 2-year experience. Methods: Electronic referrals for patients (pts) treated with ICIs at an academic center were sent to the IR-Tox team between 08/2017-12/2019. Demographic, treatment, and irAE data, including in-person consultations and hospitalizations, were collected in an IRB-approved database. Results: The IR-Tox Team received 270 referrals from 227 discrete pts (outpt: 64% inpt: 36%). Median age was 63 years (range: 3-91), 52% were male, 23% had a prior autoimmune condition, and 28% had a prior irAE. Pts had thoracic (30%), gastrointestinal (18%) or melanoma/skin cancers (17%). The majority of pts received ICI monotherapy (56%) vs. combination (44%). Referrals were for suspected irAE (92%, 209/227) or pre-ICI assessment for known autoimmune disease (8%, 18/227). Referrals for confirmed irAEs (147/209) were mainly for high-grade toxicity (G1 = 8%, 2 = 37%, 3 = 54%), 49% were hospitalized (72/147), and 86% (127/147) improved/resolved. In those who did not have a confirmed irAE (n = 62), an alternative medical condition was the most frequent diagnosis (27%, 17/62). The most common irAEs were pneumonitis (51%), dermatitis (11%), arthritis (7%), hepatitis (6%), and colitis (5%). In the entire cohort, organ-specialists were consulted electronically in 92% of pts (209/227), and 73% were subsequently seen in-person (166/227), with the majority (90/166; 54%) undergoing an invasive diagnostic procedure to confirm the irAE. Of outpatients referred, 64% (94/146) required subsequent in-person consults from organ-specialists and only 12% (18/146) were hospitalized. After all irAE-hospitalizations, continued irAE management was delivered in conjunction with organ-specialists in 51% of cases (32/72). Conclusions: A multidisciplinary IR-Tox program is a utilized service that has assisted in irAE identification and management over 2+ years. Use of an electronic referral platform may impact subsequent need for in-person specialist consultations and/or hospitalizations for irAEs. Ongoing management of complex irAEs is now commonly delivered in a multidisciplinary fashion.

138 Background: Immune checkpoint inhibitors (ICIs) are anti-cancer agents now in routine clinical practice, and may cause immune-related adverse events (irAEs). The proportion of inpatient admissions for irAEs, spectrum of toxicities, management and outcomes are not well described. Methods: Patients with solid tumors admitted to the inpatient oncology service at a tertiary academic center over 3 months, were identified. Patient demographics, treatment details, irAE event and management data, were collected for those who received ICIs, in an IRB-approved database. The diagnosis of irAEs was confirmed by the treating physician and oncologist. Associations between clinical details and irAEs were evaluated using Fisher's exact test. Results: We identified 240 inpatient oncology patients: 53 (22.1%) had received ICIs, and 25% (13/53) were admitted for irAEs. The majority of irAEs requiring admission were high grade (CTCAE grade 1-2: 6/13, 46%; grade 3+: 7/13, 54%), and included: colitis (31%), pneumonitis (23%), skin rash (8%), fever (8%), pancreatitis (8%), fatigue (8%), and renal transplant rejection (8%). Treatment for irAEs included: ICI withhold (2/13, 15%), oral/IV corticosteroids (10/13, 76%), and infliximab (1/13, 8%); with 85% of patients requiring subspecialty consultations. Those with irAEs had a shorter median length of stay vs. other inpatients (5 vs. 6 days). Most irAEs resolved/improved (11/13, 85%), while 15% worsened (1/13) or resulted in patient death (1/13). There was a numerically higher risk of any/grade3+ irAEs for those: treated with combination vs monotherapy (33% vs 23%; 100% vs 40%), age > 65 vs < 65 (33% vs 15%; 56% vs 50%), and former/current vs. never smokers (31% vs 19%; 63% vs 40%), however differences were not statistically significant. Conclusions: Patients with irAEs constitute a notable proportion of inpatient oncology admissions, with a higher incidence than in reported clinical trials. Initial data suggest that patients treated with combination ICIs, aged > 65, and former/current smokers may be more likely to be admitted for irAEs. The majority of irAE admissions require subspecialty consultations, signifying a growing need for multidisciplinary irAE management.