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

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.

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

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.

scholarly journals 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

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.

scholarly journals Clinical and Hematological Predictors of High-Grade Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors

2021 ◽  
Vol 13 (5) ◽  
pp. 268-275
Author(s):  
Ashish Manne ◽  
Madhuri S. Mulekar ◽  
Daisy E. Escobar ◽  
Alhareth Alsayed ◽  
Gaurav Sharma ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
High Grade

scholarly journals Safety and Efficacy of the Rechallenge of Immune Checkpoint Inhibitors After Immune-Related Adverse Events in Patients With Cancer: A Systemic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Qing Zhao ◽  
Jianwei Zhang ◽  
Lingyi Xu ◽  
Huaxia Yang ◽  
Naixin Liang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Systemic Review ◽  
High Grade ◽  
Safety And Efficacy ◽  
Patients With Cancer ◽  
Significant Difference

IntroductionLittle evidence exists on the safety and efficacy of the rechallenge of immune checkpoint inhibitors (ICIs) after immune-related adverse events (irAEs) in patients with cancer.MethodsWe searched PubMed, Web of Science, Embase, and Cochrane for articles on ICI rechallenge after irAEs for systemic review and meta-analysis. The outcomes included the incidence and associated factors for safety and objective response rate (ORR) and disease control rate (DCR) for efficacy.ResultsA total of 789 ICI rechallenge cases from 18 cohort studies, 5 case series studies, and 54 case reports were included. The pooled incidence of all-grade and high-grade irAEs after rechallenge in patients with cancer was 34.2% and 11.7%, respectively. Compared with initial ICI treatment, rechallenge showed a higher incidence for all-grade irAEs (OR, 3.81; 95% CI, 2.15–6.74; p < 0.0001), but similar incidence for high-grade irAEs (p > 0.05). Types of initial irAEs (pneumonitis and global irAEs) and cancer (non-small cell lung cancer and multiple cancer) recapitulated these findings. Gastrointestinal irAEs and time interval between initial irAEs and ICI rechallenge were associated with higher recurrence of high-grade irAEs (p < 0.05), whereas initial anti-PD-1/PD-L1 antibodies were associated with a lower recurrence (p < 0.05). Anti-PD-1/PD-L1 antibodies rechallenge was associated with a lower all-grade irAE recurrence (p < 0.05). The pooled ORR and DCR after rechallenge were 43.1% and 71.9%, respectively, showing no significant difference compared with initial ICI treatment (p > 0.05).ConclusionsICI rechallenge after irAEs showed lower safety and similar efficacy outcomes compared with initial ICI treatment.Systematic Review RegistrationPROSPERO, identifier CRD42020191405.

scholarly journals IMMU-04. IMMUNE-RELATED ADVERSE EVENTS STRONGLY PREDICT SUPERIOR OUTCOMES IN BRAIN METASTASES PATIENTS RECEIVING LOCAL TREATMENT AND IMMUNE CHECKPOINT INHIBITORS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii105-ii105
Author(s):  
Alexander Hulsbergen ◽  
Asad Lak ◽  
Yu Tung Lo ◽  
Nayan Lamba ◽  
Steven Nagtegaal ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Adverse Events ◽  
Brain Metastases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Local Treatment ◽  
Sensitivity Analyses ◽  
Immortal Time Bias ◽  
The Brain

Abstract INTRODUCTION In several cancers treated with immune checkpoint inhibitors (ICIs), a remarkable association between the occurrence of immune-related adverse events (irAEs) and superior oncological outcomes has been reported. This effect has hitherto not been reported in the brain. This study aimed to investigate the relation between irAEs and outcomes in brain metastases (BM) patients treated with both local treatment to the brain (LT; i.e. surgery and/or radiation) and ICIs. METHODS This study is a retrospective cohort analysis of patients treated for non-small cell lung cancer (NSCLC) BMs in a tertiary institution in Boston, MA. Outcomes of interest were overall survival (OS) and intracranial progression-free survival (IC-PFS), measured from the time of LT. Sensitivity analyses were performed to account for immortal time bias (i.e., patients who live longer receive more cycles of ICIs and thus have more opportunity to develop an irAE). RESULTS A total of 184 patients were included; 62 (33.7%) were treated with neurosurgical resection and 122 (66.3%) with upfront brain radiation. irAEs occurred in 62 patients (33.7%). After adjusting for lung-Graded Prognostic Assessment, type of LT, type of ICI, newly diagnosed vs. recurrent BM, BM size and number, targetable mutations, and smoking status, irAEs were strongly associated with better OS (HR 0.33, 95% CI 0.19 – 0.58, p < 0.0001) and IC-PFS (HR 0.41; 95% CI 0.26 – 0.65; p = 0.0001). Landmark analysis including only patients who received more than 3 cycles of ICI (n = 133) demonstrated similar results for OS and IC-PFS, as did sensitivity analysis adjusting for the number of cycles administered (HR range 0.36 – 0.51, all p-values < 0.02). CONCLUSIONS After adjusting for known prognostic factors, irAEs strongly predict superior outcomes after LT in NSCLC BM patients. Sensitivity analysis suggests that this is unlikely due to immortal time bias.

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