scholarly journals P366 Long-term evolution of gastrointestinal immune-related adverse events (GI-IrAE) induced by immune checkpoint inhibitors (ICI)

2018 ◽  
Vol 12 (supplement_1) ◽  
pp. S289-S290
Author(s):  
A de Malet ◽  
G Antoni ◽  
E Soularue ◽  
M Collins ◽  
L Marthey ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Long Term Evolution ◽  
Term Evolution

Association between immune-related adverse events and long-term survival outcomes in patients treated with immune checkpoint inhibitors

2020 ◽  
Vol 132 ◽  
pp. 61-70 ◽  
Author(s):  
Denis Maillet ◽  
Pauline Corbaux ◽  
Jean-Jacques Stelmes ◽  
Stéphane Dalle ◽  
Myriam Locatelli-Sanchez ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Survival Outcomes ◽  
Term Survival ◽  
Long Term Survival

scholarly journals FRI0494 RHEUMATIC IMMUNE RELATED ADVERSE EVENTS OF CHECKPOINT INHIBITORS: A RETROSPECTIVE REVIEW OF 70 PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 845.2-846
Author(s):  
T. Lenfant ◽  
L. Calabrese ◽  
C. Calabrese
Keyword(s):  
Adverse Events ◽  
Prospective Studies ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Clinical Aspects ◽  
Link Type ◽  
Conventional Dmards

Background:Immune Checkpoint inhibitors (ICI) have revolutionized cancer therapy by achieving remarkable survival benefits however, at the cost of a myriad of immune-related adverse events (irAEs)[1]. Rheumatic irAE can develop in 5-10% of patients although the true incidence is unknown given the lack of prospective studies [2]. Symptoms are heterogenous and probably underreported with few data available about their management and outcome [3].Objectives:To describe the clinical, biological, and radiological features of the largest cohort of rheumatic irAEs from ICI along with their therapeutic management, outcome and follow-up in real-world practice.Methods:A referral process for emergent rheumatic irAEs was initiated in February 2016 between the oncology and rheumatology departments at the Cleveland Clinic Foundation. All patients were evaluated by authors CC and/or LHC. Patients’ characteristics were retrospectively collected from medical charts after IRB approval.Results:70 patients referred for one or more rheumatic irAEs between February 2016 and January 2020 were included. 66% were male, median age was 60.8 years. Among them, 24 (34%) had pre-existing rheumatic complaints. Melanoma was the most frequent malignancy (56%). ICI therapy included anti-CTLA4 (40%), anti-PD1/L1 (79%), and dual therapy ipilimumab/nivolumab (41%). Rheumatic irAE occurred in a median 4 months after ICI initiation, with phenotypes including inflammatory arthritis (32 patients), sicca-like symptoms (12), polymyalgia rheumatica-like (7), and myositis (2). Oral, intravenous or intraarticular glucocorticoids (GC) were administered to 54 patients (77%). Of these 54 patients, 22 (41%) required long term GC, 19 had bone density scan and 15 received pneumocystis (PJP) prophylaxis. One PJP case, 1 osteoporotic fracture and 2 avascular necrosis cases were reported. 16 patients received conventional DMARDS (23%) and 9 received biologics (13%). ICI therapy was held for rheumatic irAE in 31% of cases and for another systemic irAE in 29%. Median follow-up was 13.6 months, at end of follow-up 51 patients were still on treatment for rheumatic irAE and 41% of them were still symptomatic despite ongoing treatment.Conclusion:Rheumatic irAEs are heterogeneous and often chronic requiring prolonged immunomodulatory therapy. Prospective studies are required to define optimal management of rheumatic irAEs that maintain long-term oncologic outcomes.References:[1]Suarez-Almazor ME, Kim ST, Abdel-Wahab N, Diab A. Review: Immune-Related Adverse Events With Use of Checkpoint Inhibitors for Immunotherapy of Cancer. Arthritis Rheumatol 2017;69:687–99.https://doi.org/10.1002/art.40043.[2]Abdel-Wahab N, Suarez-Almazor ME. Frequency and distribution of various rheumatic disorders associated with checkpoint inhibitor therapy. Rheumatol (United Kingdom) 2019;58:vii40–8.https://doi.org/10.1093/rheumatology/kez297.[3]Kostine M, Rouxel L, Barnetche T, Veillon R, Martin F, Dutriaux C, et al. Rheumatic disorders associated with immune checkpoint inhibitors in patients with cancer-clinical aspects and relationship with tumour response: a single-centre prospective cohort study. Ann Rheum Dis 2018;77:393–8.https://doi.org/10.1136/annrheumdis-2017-212257.Disclosure of Interests:Tiphaine Lenfant: None declared, Leonard Calabrese Consultant of: AbbVie, GSK, Bristol-Myers Squibb, Genentech, Janssen, Novartis, Sanofi, Horizon, Crescendo, and Gilead, Speakers bureau: Sanofi, Horizon, Crescendo, Novartis, Genentech, Janssen, and AbbVie, cassandra calabrese Consultant of: AbbvieGSK, Speakers bureau: Sanofi-Genzyme

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.

scholarly journals SAT0540 ONE-YEAR OUTCOMES AFTER RHEUMATIC IMMUNE-RELATED ADVERSE EVENTS FROM CHECKPOINT INHIBITORS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1227.2-1227
Author(s):  
E. Berard ◽  
T. Barnetche ◽  
L. Rouxel ◽  
C. Dutriaux ◽  
L. Dousset ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Symptomatic Treatment ◽  
Musculoskeletal Symptoms ◽  
Day Range ◽  
One Year

Background:Description and initial management of rheumatic immune-related adverse-events (irAEs) from cancer immunotherapies have been reported by several groups but to date, few studies have evaluated the long-term outcomes and management of rheumatic irAEs (1).Objectives:To describe the long-term management and assess the one-year outcomes of patients who experienced rheumatic immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICI).Methods:This was a single-centre prospective observational study including patients referred for musculoskeletal symptoms while treated with ICI. After baseline rheumatological evaluation defining the clinical entity presented, follow-up visits were organised according to the type and severity of irAE. At one year, persistence of irAE, ongoing treatment, as well as cancer outcomes were assessed.Results:63 patients were included between September 2015 and June 2018. 24 patients (38%) presented with non-inflammatory musculoskeletal conditions managed with short-term symptomatic treatment and did not require specific follow-up. 39 patients (62%) experienced inflammatory manifestations, mimicking either rheumatoid arthritis (RA, n=19), polymyalgia rheumatica (PMR, n=16), psoriatic arthritis (PsA, n=3) and one flare of a preexisting axial spondyloarthritis. Overall, 32 patients (82%) received systemic glucocorticoids, with a median rheumatic dosage of 15mg/day (range: 5-60mg/day). None of the patients had to permanently discontinue ICI therapy for rheumatic irAE. 20 patients (67%) were still receiving glucocorticoids at one year, with a median dosage of 5mg/day (range: 2-20mg/day). Glucocorticoids were more frequently discontinued for patients with RA-like condition (44%) than PMR-like condition (23%), but no other predictive factor of glucocorticoids withdrawal could be identified. At one year, overall survival and progression-free survival were comparable between patients who were still receiving glucocorticoids for rheumatic irAE and patients who have discontinued. Eight patients required csDMARDs.Conclusion:At one year, a majority of patients required long-term low-dose glucocorticoids for chronic rheumatic irAE, which seems not altering oncological control.References:[1]Braaten TJ, Brahmer JR, Forde PM, et al. Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation. Ann Rheum Dis. 2019 Sep 20.Disclosure of Interests:None declared

scholarly journals Questionnaire-based detection of immune-related adverse events in cancer patients treated with PD-1/PD-L1 immune checkpoint inhibitors

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Luisa Maria Griewing ◽  
Claudia Schweizer ◽  
Philipp Schubert ◽  
Sandra Rutzner ◽  
Markus Eckstein ◽  
...  
Keyword(s):  
Adverse Events ◽  
Cancer Patients ◽  
Weight Change ◽  
Immune Checkpoint ◽  
Detection Rate ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Patient Questionnaire ◽  
Organ Specific ◽  
Tumor Entities

Abstract Background Immune checkpoint inhibitors (ICI) have become standard treatment in different tumor entities. However, safe treatment with ICI targeting the PD-1/PD-L1 axis requires early detection of immune-related adverse events (irAE). There exist different questionnaires of drug manufacturers for the detection of irAE that have not been validated so far. Methods The prospective non-interventional ST-ICI trial studied treatment with PD-1/PD-L1 ICI alone or combined with radiotherapy. In the current analysis, the detection rate of self-reported irAE with a patient questionnaire containing 41 different questions was compared to clinician-reported irAE. Results Between April 2017 and August 2019, a total of 104 patients were prospectively enrolled. NSCLC (44%) and HNSCC (42%) were the most frequent tumor entities. A total of 784 questionnaires were collected. A total of 29 irAE were reported by clinicians. The most frequent irAE was hypothyroidism (9%), followed by skin reactions (5%), hepatitis (4%), diarrhea (3%), and pneumonitis (3%). Questions that became significantly more often positive at time points of clinician-reported irAE were “weight change”, “difficulty to grip things”, “bloody or mucous stool” and “insomnia”. Self-reported organ-specific questions detected at least 50% of clinician-reported irAE of gastrointestinal, lung, endocrine, and skin irAE. It was not possible to detect hepatic irAE with the questionnaire. Conclusion Questionnaires can help to detect gastrointestinal, lung, endocrine, or skin irAE, but not hepatic irAE. Questions on “weight change” and “insomnia” may help to increase the detection rate of irAE, besides organ-specific questions. These results are a valuable contribution to the future development of a specific and practicable questionnaire for early self-reported detection of irAE during ICI therapy in cancer patients. Trial registration ClinicalTrials.gov, NCT03453892. Registered on 05 March 2018.

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