Immune checkpoint inhibitor induced hepatitis: Risk factors, outcomes, and impact on survival.

e14525 Background: Immune checkpoint inhibitors (ICIs) have improved the survival of patients with multiple cancer types, however ICI treatment is associated with a unique set of immune-related adverse events (irAEs) that can affect any organ. Few studies have evaluated the risk factors and outcomes of ICI induced hepatitis (ICIH). Methods: We utilized an institutional database of patients with advanced cancers treated with ICI between 2011 and 2017 at The OSU Comprehensive Cancer Center to identify patients with ICIH. Any patient who received at least one dose of ICI alone or in combination with other systemic therapies either as part of clinical trial or standard of care were included. Clinical data were extracted through chart abstraction. irAEs were graded using the Common Terminology Criteria for Adverse Events v5. Overall survival (OS) was calculated from the date of ICI initiation to death from any cause or the date of the last follow-up. OS with 95% confidence intervals were estimated using the Kaplan–Meier method. OS was also evaluated by occurrence of ICIH using the log-rank test. Results: We identified 1,096 patients treated with at least one dose of ICI. Most common cancers included lung (n=224, 20%) and melanoma (n=342, 31%). The most common ICIs were PD1/L1 (n=774, 71%) and CTLA-4 inhibitors (n=195, 18%). ICIH of any grade occurred in 64 (6%) patients. Overall, 46 (71%) were male and median age was 60 years. Severity of hepatitis was grade 1-2 in 30 patients (47%) (Table 1). The incidence of ≥grade 3 ICIH in the entire cohort was 3.1%. Median time to ICIH diagnosis was 63 days. ICIH occurred alone in 24 patients, and co-occurred with other irAEs in 40 patients. The most common co-occurring irAEs were pneumonitis (n=7); colitis (n=15), thyroid abnormality (n=14); and dermatitis (n=15). ICIH was more common in women (p=0.038), in patients treated with combination ICIs (p<0.001), and among patients receiving first line therapy (p=0.018). Patients who developed ICIH had significantly longer OS than patients who did not develop ICIH; there was no difference in OS between patients with ≥grade 3 ICIH vs grade 1-2 (Table). 33 out of 34 patients with ≥grade3 ICIH were treated with steroids; 3 received mycophenolate and one received infliximab. Of patients with ≥grade 3 ICIH, 11 resumed ICI therapy without recurrent ICIH. Conclusions: Female sex, combination immunotherapy, and line of therapy were associated with ICIH. Patients with ICIH had improved clinical outcomes compared to those that did not develop ICIH, even those with higher grade toxicity. Further study is needed to assist in developing risk stratification models and optimal treatment for ICIH. OS of patients with and without immune checkpoint inhibitor hepatitis.[Table: see text]

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Expansion of pharmacist clinical services to optimize the management of immune checkpoint inhibitor toxicities

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155218817937 ◽

2019 ◽

Vol 25 (4) ◽

pp. 954-960 ◽

Cited By ~ 4

Author(s):

Catherine E Renna ◽

Elizabeth N Dow ◽

Jason J Bergsbaken ◽

Ticiana A Leal

Keyword(s):

Adverse Events ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Early Recognition ◽

Management Program ◽

Cancer Center ◽

Caregiver Education

Introduction The development of immune checkpoint inhibitors has revolutionized cancer treatment and is now a part of the treatment paradigm for several malignancies. Although immune checkpoint inhibitors are generally well tolerated, treatment is associated with immune-related adverse events, some serious and potentially life threatening. Early identification and prompt appropriate management of immune-related adverse events are crucial to prevent morbidity and mortality. The complexity and severity of immune-related adverse events require interdisciplinary collaboration to optimize care. Patient and caregiver education and continued communication between patients and members of the oncology care team are vital for timely recognition and successful management of immune-related adverse events. The objective of this program is to provide a proof of concept; a pharmacist-led immune checkpoint inhibitor management program will increase early recognition and management of immune-related adverse events through patient and caregiver education and proactively assessing patients for toxicities. Methods At the University of Wisconsin Carbone Cancer Center, we developed and implemented a pharmacist-driven program, referred to as the immune checkpoint inhibitor program, which aimed to ensure patient and caregiver education and continuous monitoring of immune-related adverse events. This program utilized pharmacist–patient encounters to improve patient and caregiver education and follow-up monitoring. The design and implementation are detailed. Pharmacist interventions and patient outcomes were evaluated. Results At interim analysis, 47 patients were enrolled in the program and pharmacists completed 34 interventions on 26 patients. Pharmacists are well positioned to educate patients and caregivers on immune checkpoint inhibitor therapy and provide proactive monitoring to detect immune-related adverse events. We hypothesize that the interventions made by pharmacist may lead to earlier recognition and treatment of immune-related adverse events.

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Immune checkpoint inhibitor-related thrombocytopenia: Incidence, risk factors, and effect on overall survival.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e14549 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e14549-e14549

Author(s):

Tyler Haddad ◽

Songzhu Zhao ◽

Mingjia Li ◽

Sandip H. Patel ◽

Andrew Johns ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

Adverse Events ◽

Immune Checkpoint ◽

Clinical Decision Making ◽

Comprehensive Cancer Center ◽

Cancer Center ◽

Cancer Type ◽

Grade 3 ◽

Line Of Therapy

e14549 Background: Immune checkpoint inhibitors (ICI) are a standard of care therapy for patients with many different cancers. ICI are generally well tolerated but are associated with unique immune-related adverse events (irAEs). Immune-related thrombocytopenia (irTCP) is an understudied and poorly understood toxicity and risk factors for irTCP are unknown. Although other irAE have been associated with clinical benefit, little data is available regarding either risk of irTCP or the effect of irTCP on clinical outcomes of patients treated with ICI. Methods: We conducted a retrospective review of sequential patients with any solid or hematologic cancer treated with ICI between 2011 and 2017 at The Ohio State University Comprehensive Cancer Center. All patients who received ICI alone or in combination with other systemic therapy in any line of treatment were included; those with thrombocytopenia ≥ grade 3 at baseline were excluded. Thrombocytopenia grading was performed utilizing the Common Terminology Criteria for Adverse Events version 5.0. Attribution to ICI was defined as timing after ICI initiation, lack of alternative causes, and improvement with either holding treatment or use of immune suppressive therapy. Overall survival (OS) was calculated from the date of initiation of ICI to death from any cause or date of the last follow-up examination. Cox proportional hazard models were used to examine the associations between platelet categories with OS. Median OS was estimated using Kaplan-Meier method with 95% CI. Results: We identified 1,038 patients treated with ICI therapy after excluding patients with baseline thrombocytopenia. The median age was 61.4; 613 (59.1%) were male and 613 (59.1%) had history of smoking. The most common cancer types were melanoma (n = 337, 32.5%), lung (n = 213, 20.5%), and renal cell carcinoma (n = 114, 11%). The most common ICI were PD1/L1 (n = 729, 70.2%) and CTLA4 (n = 191, 18.4%). Overall, 89 (8.6%) patients developed grade ≥3 thrombocytopenia; twenty were attributed to ICI (1.93% overall). Patients who developed ≥3 irTCP had worse overall survival compared to those whose thrombocytopenia was unrelated to ICI (5.45 vs 11.3 months; HR. 2.077, 95% CI 1.231, 3.503; log-rank p = 0.005). Patients with ≥3 irTCP also had shorter survival compared to those without thrombocytopenia of any etiology (5.45 vs 13.3 months; HR 2.247, 95% CI: 1.414, 3.571; p < 0.001). irTCP was more common among those treated with PD1/L1 (p = 0.03) but was not associated with cancer type, smoking status, age, gender, race, or line of therapy. Conclusions: Type of immunotherapy is related to irTCP, whereas cancer type and line of therapy are not. Unlike other irAEs, we found that irTCP was associated with shorter overall survival. These findings provide important insight into a poorly understood and rare toxicity. irTCP should be evaluated in more extensive studies to better inform clinical decision making.

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Clinical Outcomes of Cetuximab and Paclitaxel after Progression on Immune Checkpoint Inhibitors in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Medicina ◽

10.3390/medicina57111151 ◽

2021 ◽

Vol 57 (11) ◽

pp. 1151

Author(s):

Shinsuke Suzuki ◽

Satoshi Toyoma ◽

Yohei Kawasaki ◽

Koh Koizumi ◽

Nobuko Iikawa ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Adverse Events ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Neck Squamous Cell Carcinoma ◽

Grade 3

Background and Objectives: In recent years, the effectiveness of chemotherapy after immune checkpoint inhibitor administration has attracted attention in various cancers, including head and neck cancers. However, individual assessments of the administered chemotherapy regimens are insufficient. This study aimed to evaluate the efficacy and safety of chemotherapy after immune checkpoint inhibitor administration in recurrent metastatic head and neck cancer by focusing on a single regimen. Materials and Methods: We retrospectively reviewed clinical and radiological data from the medical records of 18 patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who received systemic chemotherapy with weekly cetuximab and paclitaxel (Cmab + PTX) after progression following immune checkpoint inhibitor (ICI) therapy. The objective response rate (ORR) and disease control rate (DCR) were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Adverse events (AEs) were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Results: In all patients, the ORR, DCR, median PFS, and median OS were 44.4%, 72.2%, 3.8 months, and 9.6 months, respectively. Regarding AEs, three patients developed grade 3 neutropenia. Grade 3 anemia, paronychia, asthenia, and peripheral neuropathy were observed in one patient each. There were no treatment-related deaths. Conclusions: Cmab + PTX was shown to maintain high efficacy and acceptable safety for R/M HNSCC that progressed after ICI therapy. Further research is needed to establish optimal treatment sequences and drug combinations for recurrent R/M HNSCC.

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Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease

Journal of Clinical Oncology ◽

10.1200/jco.19.01674 ◽

2020 ◽

Vol 38 (6) ◽

pp. 576-583 ◽

Cited By ~ 23

Author(s):

Hamzah Abu-Sbeih ◽

David M. Faleck ◽

Biagio Ricciuti ◽

Robin B. Mendelsohn ◽

Abdul R. Naqash ◽

...

Keyword(s):

Adverse Events ◽

T Lymphocyte ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Cytotoxic T Lymphocyte ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Inhibitor Therapy ◽

Checkpoint Inhibitor Therapy ◽

Inflammatory Bowel

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.

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Biomarkers to predict immune-related adverse events with checkpoint inhibitors.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.8_suppl.131 ◽

2019 ◽

Vol 37 (8_suppl) ◽

pp. 131-131 ◽

Cited By ~ 3

Author(s):

Lia Head ◽

Nicholas Gorden ◽

Robert Van Gulick ◽

Carol M. Amato ◽

Ashley Frazer-Abel ◽

...

Keyword(s):

Adverse Events ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Inhibitor Therapy ◽

Tnf Alpha ◽

Immune Markers ◽

Ifn Alpha ◽

Checkpoint Inhibitor Therapy

131 Background: Immune-related adverse events (IRAE) occur commonly with immune checkpoint inhibitor therapy for the treatment of cancer, although the specific event and severity can vary widely. Little is known regarding factors that may predict which patients will develop an IRAE. The goal of this study is to identify blood biomarkers predictive of IRAE associated with immune checkpoint inhibitor therapy. Methods: Blood samples collected from patients with melanoma prior to receiving therapy with immune checkpoint inhibitors were obtained from the University of Colorado Skin Cancer Biorepository. Testing for a panel of autoantibodies and cytokines (ANA, CCP 3.1, IL-1 beta, IL-2, IL-6, IL-10, IL-12, IP-10, MCP-1, TNF alpha, IFN alpha 2, IFN gamma) in serum samples from patients who had at least one documented IRAE was performed by Exsera BioLabs. Descriptive statistics were used to evaluate biomarker levels in relation to type, grade, and number of adverse events. Results: Pre-treatment samples from 45 patients were evaluated. Median age was 55; 26 were male and 19 were female. The most common IRAEs were colitis (n = 22), thyroid dysfunction (n = 21), and dermatitis (n = 20). Most IRAEs were grade 2 in severity, and the majority of patients (n = 36) experienced more than 1 IRAE. TNF alpha was elevated in 60% of patient samples, while IFN alpha 2 was elevated in 44%. Borderline ANA was detected in 27% of samples and ANA was positive in 11%. No samples had elevation of IL-2. Between 9% and 18% of samples had elevation of the other immune markers tested (IFN gamma, IL-1 beta, IL-6, IL-10, IL-12, and CCP 3.1). Elevation of TNF alpha and IFN alpha 2 were associated with higher grades of IRAEs. No associations between immune markers and the number or type of adverse events in an individual patient were noted. Results from 15 patients who did not have a documented IRAE on immune checkpoint inhibitor therapy are currently pending to confirm these findings are unique to patients developing IRAE. Conclusions: This preliminary data suggests that baseline elevations of TNF alpha and IFN alpha 2 may predict development of IRAEs with immune checkpoint inhibitor therapy. Results from samples from patients who did not develop an IRAE on therapy will be reported at the meeting.

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Immune Checkpoint Inhibitor Associated Hepatotoxicity in Primary Liver Cancer Versus Other Cancers: A Systematic Review and Meta‐Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.650292 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jianyang Fu ◽

Wang-Zhong Li ◽

Nicole A. McGrath ◽

Chunwei Walter Lai ◽

Gagandeep Brar ◽

...

Keyword(s):

Solid Tumors ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Primary Liver Cancer ◽

Meta Analysis ◽

High Grade ◽

Liver Cancers ◽

Grade 3

BackgroundOverall risks of hepatotoxicity with immune checkpoint inhibitors (ICIs) have yet to be compared in primary liver cancers to other solid tumors.MethodsWe reviewed data from the PubMed, Embase, and Scopus databases, and assessed the risk of hepatotoxicity associated with ICIs.ResultsA total of 117 trials were eligible for the meta‐analysis, including 7 trials with primary liver cancers. The most common hepatotoxicity was ALT elevation (incidence of all grade 5.29%, 95% CI 4.52-6.20) and AST elevation (incidence of all grade 5.88%, 95% CI 4.96-6.97). The incidence of all grade ALT and AST elevation was 6.01% and 6.84% for anti-PD‐1 (95% CI 5.04-7.18/5.69-8.25) and 3.60% and 3.72% for anti-PD-L1 (95% CI 2.72-4.76/2.82-4.94; p< 0.001/p<0.001). The incidence of ≥ grade 3 ALT and AST elevation was 1.54% and 1.48% for anti-PD‐1 (95% CI 1.19-1.58/1.07-2.04) and 1.03% and 1.08% for anti-PD-L1 (95% CI 0.71-1.51/0.80-1.45; p= 0.002/p<0.001). The incidence of all grade ALT and AST elevation was 13.3% and 14.2% in primary liver cancers (95% CI 11.1-16.0 and 9.93-20.36) vs. 4.92% and 5.38% in other solid tumors (95% CI 4.21-5.76 and 4.52-5.76 in other solid tumors; p <0.001/p<0.001).ConclusionOur study indicates that anti-PD-1 is associated with a higher risk of all‐ and high‐grade hepatotoxicity compared to anti-PD-L1, and primary liver cancers are associated with a higher risk of all‐ and high‐grade hepatotoxicity compared to other solid tumors.

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Endocrinopathies Associated with Immune Checkpoint Inhibitor Cancer Treatment: A Review

Journal of Clinical Medicine ◽

10.3390/jcm9072033 ◽

2020 ◽

Vol 9 (7) ◽

pp. 2033

Author(s):

Naoko Okura ◽

Mai Asano ◽

Junji Uchino ◽

Yoshie Morimoto ◽

Masahiro Iwasaku ◽

...

Keyword(s):

Adverse Events ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Endocrine Disorders ◽

Appropriate Treatment ◽

Generic Term ◽

Pituitary Glands

Treatment with immune checkpoint inhibitors has shown efficacy against a variety of cancer types. The effects of nivolumab and pembrolizumab on lung cancer have been reported, and further therapeutic advances are ongoing. The side effects of immune checkpoint inhibitors are very different from those of conventional cytocidal anticancer drugs and molecular targeted drugs, and they involve various organs such as the digestive and respiratory organs, thyroid and pituitary glands, and skin. The generic term for such adverse events is immune-related adverse events (irAEs). They are relatively infrequent, and, if mild, treatment with immune checkpoint inhibitors can be continued with careful control. However, early detection and appropriate treatment are critical, as moderate-to-severe irAEs are associated with markedly reduced organ function and quality of life, with fatal consequences in some cases. Of these, endocrinopathies caused by immune checkpoint inhibitors are sometimes difficult to distinguish from nonspecific symptoms in patients with advanced cancer and may have serious outcomes when the diagnosis is delayed. Therefore, it is necessary to anticipate and appropriately address the onset of endocrinopathies during treatment with immune checkpoint inhibitors. Here, we present a review of endocrine disorders caused by immune checkpoint inhibitor treatment.

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

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0639 ◽

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.

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SAT0536 IMMUNE CHECKPOINT INHIBITOR THERAPY IN PATIENTS WITH PREEXISTING SARCOIDOSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5839 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1225.2-1226

Author(s):

X. Pundole ◽

O. Lambotte ◽

M. Ramos-Casals ◽

M. Suarez-Almazor

Keyword(s):

Autoimmune Diseases ◽

Medical Record ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Inhibitor Therapy ◽

Cancer Center ◽

History Of ◽

Checkpoint Inhibitor Therapy

Background:Immune checkpoint inhibitors (ICI) have changed the treatment landscape of many cancer types, but are also associated with development of immune-related adverse events, includingde novosarcoid like reactions. However, little is known about the use of ICI therapy in patients with preexisting sarcoidosis as patients with preexisting autoimmune diseases have been systematically excluded from clinical trials of ICI therapy due to concerns of heightened toxicities. Emerging research suggests that ICI therapy can be considered in some patients with autoimmune diseases.1Objectives:To determine the risk of sarcoidosis exacerbation or flare in patients with preexisting sarcoidosis receiving ICI therapy.Methods:We conducted a retrospective cohort study of patients seen at The University of Texas MD Anderson Cancer Center between 2016-2019. Patients were included in the cohort if they received one of 7 ICI therapies (ipilimumab, nivolumab, pembrolizumab, durvalumab, avelumab, atezolizumab, or cemiplimab) and had an International Classification of Disease version 10 code of sarcoidosis (D86.*), prior to the ICI initiation, with diagnosis confirmed in medical record by treating physicians. A sarcoidosis diagnosis was considered “possible” if the medical record documented a history of sarcoidosis, “probable” if a history of biopsy proven sarcoidosis was mentioned, and “definitive” if histological evidence was available. Frequency of flares and outcomes of patients after receiving ICI were collected.Results:During the study timeframe a total of 32 patients with preexisting sarcoidosis received ICI therapy. Nine patients (28%) had a definitive diagnosis of sarcoidosis, 12 (37%) had a probable diagnosis and 11 (35%) had a possible diagnosis of sarcoidosis. The mean time between diagnosis of sarcoidosis and initiation of ICI therapy was 13 years (range: <1 to 51 years). Twenty-seven patients (84%) received monotherapy and five patients (16%) received combination or sequential ICI therapy. Of the 32 patients, one patient with a 20-year remote history of sarcoidosis, never treated, developed a clinically symptomatic exacerbation of sarcoidosis one month after the initial dose of atezolizumab, with increased hilar nodules on imaging, skin nodules, arthritis and uveitis. Biopsy of a lymph node showed non-necrotizing granulomas, and biopsy of the skin panniculitis. The patient also developed colitis thought to be an immune-related adverse event. Atezolizumab was discontinued after 3 doses. Patient was treated with prednisone and azathioprine.Conclusion:Patients with a remote history of stable sarcoidosis at the time of ICI therapy infrequently develop a flare of their sarcoidosis. The risk of flares in patients with active sarcoidosis requiring immunosuppression at the time of ICI initiation is unknown.References:[1]Kennedy LC, Bhatia S, Thompson JA, Grivas P. Preexisting autoimmune disease: implications for immune checkpoint inhibitor therapy in solid tumors. Journal of the National Comprehensive Cancer Network. 2019 Jun 1;17(6):750-7.Acknowledgments:NoneDisclosure of Interests:Xerxes Pundole: None declared, Olivier Lambotte Consultant of: BMS France, MSD, Astra Zeneca, Incyte, Manuel Ramos-Casals: None declared, Maria Suarez-Almazor: None declared

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Risk factors for immune mediated adverse events with immune checkpoint inhibitors.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.2622 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 2622-2622

Author(s):

Ari Pelcovits ◽

Hetal Mistry ◽

Rani Chudasama ◽

Sarah Andrea ◽

Humera Khurshid

Keyword(s):

Risk Factors ◽

Adverse Events ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Multinomial Logistic Regression ◽

Concurrent Chemotherapy ◽

Historical Cohort ◽

Weighted Estimates ◽

Grade 3

2622 Background: Immune checkpoint inhibitors (ICIs) are associated with unique toxicity - immune-related adverse events (irAEs). irAEs are common, occurring in nearly 30 % of patients (pts) in clinical trials. Risk factors for irAEs remain largely unknown, with limited evidence to guide risk stratification for these pts. Methods: In this historical cohort study, we identified 400 pts receiving ICIs at our institution between 1/1/2015 - 12/31/2019 and followed them until progression, death, or study end date. Using modified Poisson and multinomial logistic regression we assessed irAEs (yes/no; none/grade 1-2/grade 3-4) as a function of independent risk factors in separate models. These included age, PDL-1%, steroid use in the 2 weeks (S2wks) prior to ICI, concurrent chemotherapy, combination ICI use, and pre-ICI creatinine (Cr) and absolute lymphocyte count. We constructed sample weights using sociodemographic and clinical factors to account for confounding by indication and mortality-related censoring. Results: 367 pts (median age: 68 yrs) had complete data for analysis comprising 55% men and 89% white. 111 (31%) experienced an irAE during the study period (median time to first event: 81 days). Risk was greatest for the youngest and oldest pts on ICI. In weighted models, Pts ≤59 yrs were 3 times as likely to experience an irAE relative to those aged 60-68 (95% CI: 1.18,7.41; Table). Additionally, for each 1 unit increase in Cr, risk of irAE increased by 19% (95% CI: 1.08,1.28). Precision of weighted estimates was impacted by limited pt comparability across factors of interest and overall sample size. While not statistically significant (RR: 2.04;95% CI:0.92,4.53) 70.6% of pts on combination ICIs experienced an irAE compared with 20.3% on one ICI. Similarly, while not statistically significant, 15.4% of pts with PDL-1 >49% experienced a grade 3/4 irAE compared with 7.7% of pts with PDL-1<1%. Conclusions: In this real-world analysis of irAEs, younger age and elevated creatinine were risk factors for development of irAEs. Further research leveraging larger data sources is needed to examine PDL-1% as a potential risk factor of irAE.[Table: see text]

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