scholarly journals Immune-Related Adverse Events Requiring Hospitalization: Spectrum of Toxicity, Treatment, and Outcomes

2019 ◽  
Vol 15 (9) ◽  
pp. e825-e834 ◽  
Author(s):  
Aanika Balaji ◽  
Jiajia Zhang ◽  
Beatriz Wills ◽  
Kristen A. Marrone ◽  
Hany Elmariah ◽  
...  
Keyword(s):  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Patient Characteristics ◽  
Spectrum Management ◽  
Service Planning ◽  
Inpatient Service ◽  
High Demand ◽  
Academic Center ◽  
Increased Risk ◽  
Oncology Center

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.

Rates of immunosuppressive treatment and hospitalization after checkpoint inhibitor therapy in melanoma and lung cancer patients with autoimmune diseases.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14140-e14140
Author(s):  
David Andrew Bender ◽  
Catherine Spina ◽  
Samuel P. Heilbroner ◽  
Eric Xanthopoulos ◽  
Tony J. C. Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Autoimmune Diseases ◽  
Cancer Patients ◽  
Checkpoint Inhibitors ◽  
Oral Prednisone ◽  
Immunosuppressive Treatment ◽  
Lung Cancer Patients ◽  
Pharmacy Claims ◽  
Increased Risk

e14140 Background: Immune checkpoint inhibitors (ICIs) are known to cause immune-related adverse events. Patients with autoimmune diseases (AID) were excluded from most ICI clinical trials due to the potentially high risk of adverse effects. Data on the safety of ICIs in patients with a diagnosis of AID is therefore limited. Methods: A retrospective cohort study was conducted using a de-identified large oncology health care and pharmacy claims database with data from March 2010 until April 2017. Patients analyzed had a diagnosis of either melanoma or lung cancer and were treated with either of the anti-PD-1 inhibitors nivolumab or pembrolizumab. We assessed whether patients with AID compared with no AID were more likely to require medical interventions within 180 days of ICI therapy. We determined the percentage of patients receiving oral prednisone, IV methylprednisolone, or were hospitalized, which may represent responses to ICI toxicity. Results: 16.7% (16/96) of patients with either melanoma or lung cancer and AID received oral prednisone treatment within 180 days of ICI treatment, while 8.3% (131/1573) of patients without AID received oral prednisone during the same period. 8.4% (16/190) of patients with AID received IV methylprednisolone compared to 3.6% (79/2190) of patients without AID. Among melanoma patients, 24.1% (13/54) of patients with AID were hospitalized following ICI treatment, compared to 5.8% (28/480) of patients without ICI. Among lung cancer patients, 38.2% (52/136) of patients with AID were hospitalized compared to 31.6% (541/1711) of patients without AID. All comparisons are significant at p < 0.05 except hospitalizations in lung cancer patients. Conclusions: Patients with AID were more likely to receive interventions after ICI treatment that may represent responses to immune-related adverse events, suggesting that patients with AID are at increased risk for toxicity when being treated with ICIs.

Immune-related adverse events in advanced NSCLC treated with immunotherapy alone or concurrent chemotherapy and immunotherapy.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 83-83
Author(s):  
John Melson ◽  
Daniel Reed ◽  
Bethany J. Horton ◽  
Margaret Moore ◽  
Jacqueline Theresa Brown ◽  
...  
Keyword(s):  
Adverse Events ◽  
Proportional Hazards ◽  
Advanced Nsclc ◽  
Checkpoint Inhibitors ◽  
Therapy Group ◽  
Stage Iv ◽  
Standard Of Care ◽  
Concurrent Chemotherapy ◽  
Increased Risk ◽  
Treatment Naïve

83 Background: Concurrent chemotherapy (CTX) with checkpoint inhibitors (CPI) has become a new standard of care for treatment naïve stage IV non-small cell lung cancer (NSCLC). Little is known about the timing and pattern of immune-related adverse events (irAEs) when CTX and CPI are combined. We sought to characterize irAEs and determine if combination CTX+CPI affects time to first irAE in comparison to patients (pts) receiving CPI alone. Methods: Advanced NSCLC patients who received at least one dose of a CPI at our institution between 2015 and 2018, either alone or with CTX, were identified. Retrospective review for occurrence of irAEs and clinical outcomes was performed. Proportional hazards models were used to assess time to first irAE for CPI vs CTX+CPI and overall survival (OS) for CPI alone. Results: 149 pts were identified. 112 pts received CPI alone and 37 received CTX+CPI. The proportion of pts with at least 1 irAE was higher in the combination therapy group than the monotherapy group (59% vs 34% of patients). Time to any grade first irAE was shorter with CTX+CPI vs CPI alone (6.0 m vs 36.7 m, HR 1.8, p = 0.0304). Among pts treated with CPI alone, OS was significantly longer with any irAE (38.0 m vs 11.4 m, HR 2.9, p = 0.0026). While there were more irAEs in the CTX+CPI cohort, the frequency of irAEs by organ system was similar to previous reports. Conclusions: For patients receiving CTX+CPI, there is an increased risk of irAEs and a significantly shorter time to first irAE occurrence compared to CPI alone. Among patients receiving CPI alone, the presence of irAE was associated with a 3-fold improvement in OS. Further analysis of OS for the CTX+CPI group is planned with additional follow-up. [Table: see text]

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.

Incidence and prediction of checkpoint inhibitor immune-related nephrotoxicity.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 91-91
Author(s):  
Jonathan D Sorah ◽  
Tracy L. Rose ◽  
Roshni Radhakrishna ◽  
Vimal Derebail ◽  
Matthew I. Milowsky
Keyword(s):  
Autoimmune Disease ◽  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Retrospective Chart Review ◽  
Tumor Type ◽  
True Incidence ◽  
Platinum Based Chemotherapy ◽  
Increased Risk ◽  
Clinically Significant

91 Background: Immune checkpoint inhibitors (ICIs), through inhibition of self-tolerance, have the potential to cause immune-related adverse events that can affect any organ, including the kidneys. Our study aimed to better characterize the incidence of and predictive characteristics for immune-related nephrotoxicity. Methods: All patients at the University of North Carolina (UNC) who received ICIs between April 2014 and December 2018 for any malignancy were identified. Patients on dialysis or those who received concurrent platinum-based chemotherapy were excluded. Any patient who subsequently had a clinically significant acute kidney injury (AKI), defined as a doubling or more of baseline creatinine, was included for analysis. A retrospective chart review was performed to determine the cause of AKI. Any uncertain cases were reviewed by two nephrologists for expert consensus (R.R. and V.D.). Results: 1766 patients received an ICI during the study period. 123 (7%) patients had AKI within one year of the first ICI dose. 14 were due to immune-related nephrotoxicity (11% of patients with AKI and 0.8% of all ICI patients). Pre-existing autoimmune disease was more likely in patients with immune-related nephrotoxicity than in those with non-immune AKI (14% vs 3%, p = 0.04). Similarly, concurrent or prior other immune-related adverse events were more common in patients with immune-related AKI (57% vs 6%, p = 0.01). Patients with immune-related AKI were more likely to see a nephrologist (57% vs 23%, p = 0.007) and had a more profound increase in creatinine from baseline (median 2.6 vs 1.6, p = 0.02). Age, sex, urinalysis findings, and primary tumor type were not associated with increased risk. Conclusions: The true incidence of ICI related nephrotoxicity is difficult to ascertain due to the many confounders that contribute to AKI in this population. Severe immune-related nephrotoxicity is rare, but patients with preexisting autoimmune disease or history of immune-related adverse events are at increased risk.

scholarly journals Differential Dermatologic Adverse Events Associated With Checkpoint Inhibitor Monotherapy and Combination Therapy: A Meta-Analysis of Randomized Control Trials

2021 ◽  
Vol 12 ◽  
Author(s):  
Yang Ge ◽  
Huiyun Zhang ◽  
Nathaniel Weygant ◽  
Jiannan Yao
Keyword(s):  
Relative Risk ◽  
Combination Therapy ◽  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
High Grade ◽  
Treatment Regimens ◽  
Increased Risk ◽  
Significant Difference ◽  
Dermatologic Adverse Events

Background: As immune checkpoint inhibitors (ICIs) transition to the forefront of cancer treatment, a better understanding of immune related adverse events (IRAEs) is essential to promote safe clinical practice. Dermatologic adverse events are the most common IRAEs and can lead to drug withdrawal and decreased quality of life. This meta-analysis aimed to investigate the risk of the most prevalent dermatologic adverse events (pruritus and rash) among various ICI treatment regimens.Methods: A systematic search of electronic databases was performed to identify qualified randomized controlled trials (RCTs). Data for any grade and high grade pruritus and rash were extracted for meta-analysis. Two reviewers independently assessed methodological quality. The relative risk summary and 95% confidence interval were calculated.Results: 50 RCTs involving 29941 patients were analyzed. The risk of pruritus (2.15 and 4.21 relative risk respectively) and rash (1.61 and 3.89 relative risk respectively) developing from CTLA-4 or PD-1/-L1 inhibitor were increased compared to placebo, but this effect was not dose-dependent. PD-1/-L1 plus CTLA-4 inhibitor was associated with increased risk of pruritus (1.76 and 0.98 relative risk respectively) and rash (1.72 and 1.37 relative risk respectively) compared to either monotherapy. Compared with CTLA-4 inhibitor, PD-1/-L1 inhibitor had a significantly decreased risk of pruritus and rash in both monotherapy and combination therapy (0.65 and 0.29 relative risk respectively). No significant difference was found between PD-1/-L1 inhibitor combined with chemotherapy and PD-1/-L1 monotherapy in any grade and high grade rash (0.84 and 1.43 relative risk respectively). In subgroup analyses, PD-1 inhibitor was associated with reduced risk of pruritus and rash compared to PD-L1 inhibitor.Conclusion: Our meta-analysis demonstrates a better safety profile for PD-1/-L1 inhibitor compared to CTLA-4 inhibitor in terms of pruritus and rash among both monotherapy and multiple combination therapies. PD-L1 inhibitor may contribute to an increased risk of pruritus and rash compared to PD-1 inhibitor.

Liver injury by immune checkpoint inhibitors in patients with hepatocellular carcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 341-341 ◽  
Author(s):  
Nicola Personeni ◽  
Tiziana Pressiani ◽  
Antonio Capogreco ◽  
Arianna Dal Buono ◽  
Antonio D'Alessio ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Injury ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Subsequent Treatment ◽  
Drug Induced ◽  
Increased Risk ◽  
Grade 3

341 Background: In patients with hepatocellular carcinoma (HCC) and baseline liver dysfunction, hepatic immune-related adverse events (HIRAEs) during immunotherapy have not been adequately characterized and their impact on subsequent treatment outcomes is not known. Methods: 40 patients with advanced/unresectable HCC and Child Pugh score A have been enrolled in first and second-line clinical trials of anti-programmed cell death protein 1 (PD-1) monoclonal antibodies (mAbs). HCC etiologies were: hepatitis C (32.5%), hepatitis B (7.5%), alcohol abuse (27.5%), other (32.5%). 7 received anti-PD-1 mAbs alone and 33 received combined regimens that included anti-PD-1 mAbs plus either anti-cytotoxic T lymphocyte antigen 4 (30.4%) or tyrosine kinase inhibitors (TKIs) (54.5%), or both (15.1%). We reviewed their liver function tests and HIRAEs onset was related to time to treatment failure (TTF). Results: Overall, 12 patients (30%) developed grade ≥ 3 hepatitis according to Common Toxicity Criteria for Adverse Events v. 4.03, resulting in 4 cases of grade 2 drug-induced liver injury per DILI Working Group criteria. Time between therapy initiation and hepatitis onset was 1.4 months (0.4-2.8) and median peak aminotransferase (AT) level was 258 IU/L (85-869). Out of 6 permanent treatment discontinuations due to adverse events (AEs), 4 were linked to hepatitis. Higher AT median levels at baseline were significantly linked to grade ≥ 3 hepatitis compared with lower grades (95 IU/L vs. 36 IU/L, respectively; p = 0.008). Etiology, age, treatment did not predict HIRAEs onset. TTF in patients in patients with grade ≥ 3 hepatitis was shorter than in the whole cohort (1.4 vs. 3.8 months, p = 0.041), while overall survival did not differ (p = 0.125). Conclusions: We observed a 30% incidence of clinically significant HIRAEs. HIRAEs represent the most frequent AEs leading to treatment discontinuation in patients with HCC undergoing treatments with immune checkpoint inhibitors. Baseline AT levels may identify patients at increased risk of grade ≥ 3 hepatitis.

639 Immune-related thyroid dysfunction in patients with existing thyroid dysfunction

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A675-A675
Author(s):  
Francois Kaleta ◽  
Heather Brody ◽  
Praveen Namireddy
Keyword(s):  
New York ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Thyroid Dysfunction ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Increased Risk ◽  
Endocrinological Investigation

BackgroundThyroid dysfunction is a well known side effect of immune checkpoint blockade (ICB) and is one of the most common causes of immune-related adverse events (IRAE). The incidence varies with each individual therapy but generally estimated to be in the range between 6–18% per one study. Hypothyroidism and thyroiditis are the most common manifestations. Initial hyperthyroidism followed by hypothyroidism is another manifestation. Hypothyroidism is more common with an incidence of 10% whereas hyperthyroidism has an incidence of 5%. Less is known about the incidence of worsening thyroid dysfunction in patients with pre-existing thyroid dysfunction treated with ICB.MethodsA retrospective analysis was collected on 370 patients who received immunotherapy from April 2015 to April 2019. Of those, 212 had abnormal thyroid function tests. We analyzed a subgroup of these patients who had baseline thyroid dysfunction for worsening thyroid dysfunction after they were given ICB. Fifty-three patients were included in the analysis and had an abnormal baseline TSH at the start of immunotherapy. Type of immunotherapy, worst TSH, duration between initiation of immunotherapy to worst TSH, treatment type, and grade of abnormality as per Immune Checkpoint Inhibitor Related Adverse Events Common Terminology Criteria for Adverse Events (IRAE-CTCAE) were also recorded. Analysis was done for patients to compare likelihood of worsening TSH resulting in change in treatment for thyroid disorder.ResultsOf the identified patients (N=53) with abnormal TSH screening values outside of the institution’s normal reference range 0.35 - 4.95 uIU/ml, 45.7% (N=16) were hypothyroid and 54.3% (N=19) were hyperthyroid at baseline. Of those who were hypothyroid, 50% (N=8) had worsening TSH and 50% (N=8) had unchanged TSH during treatment. Of those who were hyperthyroid, 31.6% (N=6) had unchanged TSH, 52.6% (N=10) had worsened TSH, and 15.8% (N=3) had normalization of TSH compared to baseline. Overall 26.4% had worsening and of those 11.3% required treatment change.ConclusionsThyroid dysfunction is one of the most common IRAE’s associated with immune checkpoint inhibitors. Little is known about the impact of immunotherapy on patients with existing thyroid dysfunction. Patients who have underlying thyroid dysfunction are at an increased risk for worsening thyroid dysfunction with the use of ICB but though not unduly above the risk general population. Of those with change, only a modest percentage required an alteration of their endocrine therapy. Of interest, our data suggests a potential increased risk in patients with baseline hyperthyroidism compared to hypothyroidism which may be clinically relevant.Ethics ApprovalThe study was approved by ECU Brody School of Medicine Institution’s Ethics Board, approval number 19-000710.ReferencesBarroso-Sousa R, Barry WT, Garrido-Castro AC, et al. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMA oncology. 2018;4:173–182.Fessas P, Possamai LA, Clark J, et al. Immunotoxicity from checkpoint inhibitor therapy: clinical features and underlying mechanisms. Immunology. 2019; 2020;159:167–177.Brody HM, Macherla S, Bulumulle A, Namireddy P, Cherry CR. The real-world incidence of immunotherapy-related thyroid dysfunction: A retrospective analysis of a single center’s experience over five years. Journal of clinical oncology. 2020;38:98–98.Iyer PC, Cabanillas ME, Waguespack SG, et al. Immune-Related Thyroiditis with Immune Checkpoint Inhibitors. Thyroid (New York, N.Y.). 2018;28:1243–1251.Presotto EM, Rastrelli G, Desideri I, et al. Endocrine toxicity in cancer patients treated with nivolumab or pembrolizumab: results of a large multicentre study. Journal of endocrinological investigation. 2019; 2020;43:337–345.Chalan P, Di Dalmazi G, Pani F, De Remigis A, Corsello A, Caturegli P. Thyroid dysfunctions secondary to cancer immunotherapy. Journal of endocrinological investigation. 2017; 2018;41:625–638.Mangla A, Paydary K, Yadav U, Liu J, Lad TE. Predictors and outcomes of thyroid dysfunction with immunotherapy: A single institution observational experience. Journal of clinical oncology. 2019;37:e14134-e14134.Basak EA, van der Meer, Jan W M, Hurkmans DP, et al. Overt Thyroid Dysfunction and Anti-Thyroid Antibodies Predict Response to Anti-PD-1 Immunotherapy in Cancer Patients. Thyroid (New York, N.Y.). 2020;30:966–973.Kassi E, Angelousi A, Asonitis N, et al. Endocrine-related adverse events associated with immune-checkpoint inhibitors in patients with melanoma. Cancer medicine (Malden, MA). 2019;8:6585–6594.

scholarly journals Pericardial disease in patients treated with immune checkpoint inhibitors

2021 ◽  
Vol 9 (6) ◽  
pp. e002771
Author(s):  
Jingyi Gong ◽  
Zsofia Dora Drobni ◽  
Amna Zafar ◽  
Thiago Quinaglia ◽  
Sarah Hartmann ◽  
...  
Keyword(s):  
Pericardial Effusion ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cancer Type ◽  
Pericardial Disease ◽  
Fourfold Increase ◽  
Large Pericardial Effusion ◽  
Academic Center ◽  
Increased Risk

BackgroundThere are limited data on the occurrence, associations and outcomes of pericardial effusions and pericarditis on or after treatment with immune checkpoint inhibitors (ICIs).MethodsThis was a retrospective study at a single academic center that compared 2842 consecutive patients who received ICIs with 2699 age- and cancer-type matched patients with metastatic disease who did not receive ICI. A pericardial event was defined as a composite outcome of pericarditis and new or worsening moderate or large pericardial effusion. The endpoints were obtained through chart review and were blindly adjudicated. To identify risk factors associated with a pericardial event, we compared patients who developed an event on an ICI with patients treated with an ICI who did not develop a pericardial event. Cox proportional-hazard model and logistical regression analysis were performed to study the association between ICI use and pericardial disease as well as pericardial disease and mortality. An additional 6-week landmark analysis was performed to account for lead-time bias.ResultsThere were 42 pericardial events in the patients treated with ICI (n=2842) over 193 days (IQR: 64–411), yielding an incidence rate of 1.57 events per 100 person-years. There was a more than fourfold increase in risk of pericarditis or a pericardial effusion among patients on an ICI compared with controls not treated with ICI after adjusting for potential confounders (HR 4.37, 95% CI 2.09 to 9.14, p<0.001). Patients who developed pericardial disease while on an ICI had a trend for increased all-cause mortality compared with patients who did not develop a pericardial event (HR 1.53, 95% CI 0.99 to 2.36, p=0.05). When comparing those who developed pericardial disease after ICI treatment with those who did not, a higher dose of corticosteroid pre-ICI (>0.7 mg/kg prednisone) was associated with increased risk of pericardial disease (HR 2.56, 95% CI 1.00 to 6.57, p=0.049).ConclusionsICI use was associated with an increased risk of development of pericardial disease among patients with cancer and a pericardial event on an ICI was associated with a trend towards increase in mortality.

Increased risk of immune-related hepatitis among adolescent and young adults (AYAs) with melanoma during immunotherapy with checkpoint inhibitors (ICIs).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9584-9584
Author(s):  
Alicia Darwin ◽  
Damon R. Reed ◽  
Tawee Tanvetyanon
Keyword(s):  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Age Groups ◽  
The Elderly ◽  
Age Related ◽  
Increased Risk ◽  
Melanoma Patients ◽  
Grade 3 ◽  
Elderly Cohort ◽  
Investigational Agents

9584 Background: Melanoma is the second most common malignancy affecting AYA patients after lymphoma. Nevertheless, AYA melanoma does constitute a minority of all melanoma cases. Additionally, the AYA population is not well represented in prospective clinical trials, including immunotherapy trials. While previous research has demonstrated the efficacy of ICIs across age groups, it remains unclear if toxicity profiles will be similar. In the general population, age-related changes in the immune milieu result in differential incidences of autoimmune diseases by age. This study aims to compare the toxicity profile between a cohort of AYA melanoma versus elderly melanoma patients receiving ICI therapy. Methods: In this single NCCN institutional study, electronic medical records of melanoma patients treated with ICIs between 01/2007-01/2019 were reviewed. Subjects receiving concurrent investigational agents or chemotherapy were excluded. The AYA cohort included those aged 15-40 years. The elderly cohort included those aged ≥65 years. Adverse events were coded according to CTC-AE version 5.0. Multivariable logistic regression analyses were performed. Results: Analyses included 184 treatment courses. In the AYA cohort (N = 57), median age at ICI initiation was 28.8 years (range: 17.9-39.3). In the Elderly cohort (N = 127), median age at ICI initiation was 72.3 years. More AYA patients (28.1% AYA vs. 7.9% Elderly) received ICI combination regimens. The most common adverse events amongst both cohorts were transaminitis (23.4%), rashes (49.5%), and diarrhea/colitis (20%). Incidences of pneumonitis, colitis, hypothyroidism, and hypophysitis did not differ significantly between cohorts. However, the AYA cohort experienced a higher incidence of transaminitis (38.6% AYA vs. 16.5% Elderly, p =0.001 ) and increased occurrence of treatment related hospitalization (26.3% AYA vs. 7.1% Elderly, p <0.001 ). Moreover, a higher proportion of severe grade ≥3 transaminitis occurred in the AYA group (27.3% AYA vs. 9.5% Elderly, p =0.004). While occurrence of transaminitis was significantly associated with combination ICIs, the association between AYA status and transaminitis remained significant after adjusting for ICI regimen (OR 2.75, 95% CI: 1.3-5.8). There was a trend toward shorter time to transaminitis onset among the AYA than Elderly cohort (median 53.0 vs. 74.5 days [non-parametric p= 0.28]). To date, median survival has not been reached in both groups ( p= 0.09). Conclusions: In this large cohort of AYA melanoma patients treated with ICI, we found a significantly higher incidence of immune-related transaminitis than in the Elderly cohort. Other immune-related AEs were comparable between cohorts. This finding was independent of ICI regimen. Further investigation will be needed to understand these differences between the AYA and Elderly cohorts.

A multidisciplinary immune-related toxicity (IR-Tox) program for immune-related adverse events: A two-year experience.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15074-e15074
Author(s):  
Aanika Balaji ◽  
Jiajia Zhang ◽  
Karthik Suresh ◽  
Jenna Mammen ◽  
Joanna Melia ◽  
...  
Keyword(s):  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Medical Condition ◽  
Tumor Board ◽  
Entire Cohort ◽  
Academic Center ◽  
Skin Cancers ◽  
Autoimmune Condition ◽  
Electronic Referral ◽  
Invasive Diagnostic Procedure

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.

Sign in / Sign up

Export Citation Format

Share Document