scholarly journals SAT0536 IMMUNE CHECKPOINT INHIBITOR THERAPY IN PATIENTS WITH PREEXISTING SARCOIDOSIS

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

Evaluation of arthralgias in adult oncology patients receiving immune checkpoint inhibitors

2019 ◽  
Vol 25 (8) ◽  
pp. 1867-1872 ◽  
Author(s):  
Jenessa Lee ◽  
Anastasia Graham ◽  
Amy Sion
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Retrospective Chart Review ◽  
Inhibitor Therapy ◽  
Time To Event ◽  
History Of ◽  
Checkpoint Inhibitor Therapy

Immune checkpoint inhibitors are being commonly used as anticancer therapies to treat malignancies. Immune checkpoint inhibitors have been associated with numerous immune-related adverse events (irAEs). IrAEs are well documented; however, rheumatic irAEs are infrequently reported in published literature. The objective of this single-center retrospective chart review study was to evaluate the incidence of arthralgias with immune checkpoint inhibitor therapy as well as the management of these immune-related events. Patients were included if they received one or more doses of nivolumab, pembrolizumab, atezolizumab, ipilimumab, or a combination of agents within the last year. Exclusion criteria included documented history of autoimmune disease, off-label use of immune checkpoint inhibitor, and non-FDA-approved weight-based dosing. This study included 98 patients for review and identified 11 patients that developed arthralgias with immune checkpoint inhibitor therapy. Median time to event was 63 days. Seven patients were treated with corticosteroids. Immune checkpoint inhibitor therapy was held in six patients with arthralgias. Inflammatory markers were collected for six patients and elevated in four of these cases. One patient was referred to rheumatology. The three patients who had grading of arthralgias were not managed optimally according to guideline recommendations. These findings show that 11% of patients treated with immune checkpoint inhibitors had documented arthralgias, consistent with previous reports in the literature. Also, the report shows that management and treatment of these events at our institution was not consistent between providers. Lastly, collaboration with rheumatology may be essential in managing arthralgias and other rheumatologic irAEs.

Peritoneal melanosis associated with metastatic melanoma previously treated with targeted and immune checkpoint inhibitor therapy

2021 ◽  
Vol 14 (1) ◽  
pp. e238235
Author(s):  
Kwang Kiat Sim ◽  
Katie Connell ◽  
Mayank Bhandari ◽  
David Paton
Keyword(s):  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Inhibitor Therapy ◽  
Tumour Regression ◽  
Benign Condition ◽  
Checkpoint Inhibitor Therapy ◽  
Previously Treated

Peritoneal melanosis is an uncommon benign condition, the pathophysiology of which is unclear. Macroscopically, it appears as diffuse dark brown or black pigmentation within the peritoneum, mimicking more sinister conditions such as metastatic melanoma. It has been described in a variety of contexts, but only exceedingly rarely in association with metastatic melanoma, with only two previous published case reports. We present a case of peritoneal melanosis associated with metastatic melanoma involving the spleen, previously treated with targeted and immune checkpoint inhibitor therapy. With increasing reports of melanoma regression manifesting as cutaneous tumorous melanosis in patients treated with immune checkpoint inhibitors, we postulate that, similarly, immunotherapy and tumour regression might have a role to play in the pathogenesis of the peritoneal pigmentation in this case.

scholarly journals Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease

2020 ◽  
Vol 38 (6) ◽  
pp. 576-583 ◽  
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.

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

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 131-131 ◽  
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.

scholarly journals 1-25OH2D Mediated Hypercalcemia Secondary to DISR From Immune Checkpoint Inhibitors

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A169-A170
Author(s):  
Domenic Disanti ◽  
Alissa Marr ◽  
Whitney Sears Goldner
Keyword(s):  
Immune Checkpoint ◽  
Fdg Pet ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Inhibitor Therapy ◽  
Mediastinal Lymphadenopathy ◽  
Humoral Hypercalcemia Of Malignancy ◽  
First Case ◽  
Checkpoint Inhibitor Therapy

Abstract Background: Drug induced sarcoid like reactions (DISR) have recently been described as a potential consequence of immune checkpoint inhibitor therapy. However, hypercalcemia associated with DISR has not been reported. Clinical Case: A 72 year old male presented with metastatic melanoma. He initiated therapy with Ipilimumab/Nivolumab (Ipi/Nivo). Three weeks after his first cycle he developed symptomatic hypercalcemia (calcium 14.4 mg/dL), and acute kidney injury (creatinine 3.45mg/dL), PTH 12 pg/mL, 25OHD 51, and PTHrp 0.5. He received IV fluids and IV bisphosphonates and calcium normalized to 9.1 mg/dL and creatinine 1.85 mg/dL. His Ipi/Nivo were stopped due to concern for neurotoxicity. He subsequently switched to Q3week Pembrolizumab (Pembro) and after 2 infusions, he again developed hypercalcemia (calcium 11.8 mg/dL). FDG PET demonstrated a complete radiographic response. Labs showed a 1,25OH2D of 103 pg/mL (reference range 19.9–79.3 pg/mL), PTH of 4 pg/mL and calcium of 11.4 mg/dL. He was treated with prednisone 20 mg QD. After 9 days on prednisone, 1,25OH2D was 26 pg/mL and calcium 9.4 mg/dL. He took prednisone for 3 weeks total. Repeat labs off prednisone for one week were 1,25OH2D of 38 pg/mL and calcium 9.1 mg/dL. He continued on Pembro. After being off steroids for 5 weeks, he developed body aches and swelling of the hands. 1,25OH2D increased to 100 pg/mL and calcium to 10 mg/dL. He restarted prednisone and stopped Pembro. Labs one month later showed a 1,25OH2D of 45 pg/dL while still on prednisone 10 mg qd and a normal calcium in the mid 9’s. Follow up FDG PET showed hypermetabolic bilateral hilar and mediastinal lymphadenopathy not seen on previous imaging. Ultrasound-guided lymph node biopsy revealed granulomatous lymphadenitis. He was diagnosed with DISR, secondary to immunotherapy with checkpoint inhibitors. He continues on prednisone 10 mg per day and calcium and 1,25OH2D levels have remained normal. Conclusion: This is the first case of 1,25OH2D mediated hypercalcemia as a consequence of DISR induced by immune checkpoint inhibitor therapy. Hypercalcemia in the setting of malignancy is more commonly due to humoral hypercalcemia of malignancy from PTHrp or bone metastasis, but DISR needs to be a consideration in persons with hypercalcemia on immune checkpoint inhibitor therapy, with elevated 1,25OH2D levels and low PTH and PTHrp levels.

scholarly journals Impact of age on the toxicity of immune checkpoint inhibition

2020 ◽  
Vol 8 (2) ◽  
pp. e000871
Author(s):  
Amit Samani ◽  
Shuai Zhang ◽  
Laura Spiers ◽  
Ali Abdulnabi Mohamed ◽  
Sophie Merrick ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Inhibitor Therapy ◽  
Age Cohorts ◽  
Appreciable Increase ◽  
Treatment Type ◽  
Significant Difference ◽  
Checkpoint Inhibitor Therapy

Indications for immune checkpoint inhibitor therapy are increasing. As the population ages, many patients receiving such drugs will be older adults. Such patients are under-represented in clinical trials, and therefore the safety of immune checkpoint inhibitors in this population has not been adequately assessed. A retrospective multicenter analysis of toxicities was performed in patients with advanced or metastatic solid cancers receiving anti-programmed cell death protein 1 (anti-PD-1) and/or anti-CTLA4 antibodies across three age cohorts (<65 years, 65–74 years and ≥75 years) using univariable and multivariable analyzes. Eligible patients (n=448) were divided into age cohorts: <65 years (n=185), 65–74 years (n=154) and ≥75 years (n=109). Fewer patients in the oldest cohort (7.3%) received an anti-CTLA4 antibody containing regimen compared with the younger cohorts (21.1% and 17.5%). There was no significant difference overall in all grade or ≥G3 toxicities between age cohorts. Significantly fewer patients in the older (65–74 years and ≥75 years) age cohorts discontinued treatment because of toxicity (10.1% and 7.4%) compared with in the <65 years cohort (20.5%; p=0.006). Using logistic regression, only treatment type (ipilimumab containing) was significantly associated with all grade toxicity. However, there was a significantly lower incidence of all-grade endocrine toxicity in the oldest cohort (11.0%) compared with the youngest cohort (22.7%, p=0.02; OR 0.43, 95% CI 0.21 to 0.87), while all-grade dermatological toxicity showed the reverse trend (28.4% vs 18.9%; OR 1.85, 95% CI 1.04 to 3.30). Results were corroborated in the sensitivity analysis using only data from patients who received PD-1 inhibitor monotherapy. This multicenter, real-world cohort demonstrates that immune checkpoint inhibitor therapy is safe and well tolerated regardless of age, with no appreciable increase in adverse events in older adult patients.

Analysis of tumor microenvironment characteristics in bladder cancer: implications for immune checkpoint inhibitor therapy

2021 ◽  
Author(s):  
Xingyu Chen ◽  
Haotian Chen ◽  
Dong He ◽  
YaXing Cheng ◽  
Yuxing Zhu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Tumor Microenvironment ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Cox Regression ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Prognostic Significance ◽  
Inhibitor Therapy ◽  
Checkpoint Inhibitor Therapy

Abstract Background The tumor microenvironment (TME) has a significant influence on prognosis and immunotherapy. There are no studies on the systematic analysis of bladder cancer TME and its effect on immune checkpoint inhibitor therapy. Methods We comprehensively evaluated the TME infiltration pattern of bladder cancer in 1,889 patients and conducted extensive immunogenomic analysis to explore the heterogeneity and prognostic significance of the TME of bladder cancer. The principal component analysis algorithm was used to calculate the immune cell (IC)score to quantify the level of IC infiltration. We used the receiver operating characteristic (ROC) curve, Tumor Immune Dysfunction and Exclusion (TIDE), and Subnetwork Mappings in Alignment of Pathways (SubMAP) algorithms to evaluate whether the ICscore can predict the benefits of immune checkpoint inhibitors in bladder cancer patients. Results We identified three different TME phenotypes using unsupervised clustering methods. To explore the potential biological pathways that drive the formation of these microenvironmental phenotypes, we demonstrated the clinical and pathological characteristics, biological signaling pathways, cancer immune circulation, copy number, and somatic mutation differences among the different subtypes. In addition, univariate and multivariate Cox regression analyses showed that the ICscore is a reliable and independent prognostic marker. The ICscore can also predict immune checkpoint inhibitor responsiveness as patients with higher ICscores showed a significant therapeutic advantage in immunotherapy. Conclusions This study increases our understanding of the characteristics of TME infiltration in bladder cancer and provides guidance on more effective personalized immunotherapeutic strategies.

scholarly journals Impact of Immune Checkpoint Inhibitor Therapy on The Overall Survival in Elderly Patients With Non-Small Cell Lung Cancer

2020 ◽  
Author(s):  
Minehiko Inomata ◽  
Kenji Azechi ◽  
Naoki Takata ◽  
Kana Hayashi ◽  
Kotaro Tokui ◽  
...  
Keyword(s):  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Small Cell ◽  
Inhibitor Therapy ◽  
Small Cell Lung ◽  
History Of ◽  
Checkpoint Inhibitor Therapy

Abstract Purpose: We analyzed the relationship between a history of immune checkpoint inhibitor and overall survival in patients with non-small cell lung cancer (NSCLC) aged ≥ 70 years. Methods: We conducted a retrospective analysis of the data of patients with NSCLC aged ≥70 years old who had received systemic anticancer therapy at our institution between 2015 and 2019. Results: The analysis included the data of a total of 63 patients, including 36 patients who had received immune checkpoint inhibitor therapy and 27 patients who had not received treatment with an immune checkpoint inhibitor. Univariate analysis revealed a longer overall survival in patients who had received treatment with an immune checkpoint inhibitor as compared to those who had not received treatment with an immune checkpoint inhibitor (median: 17.2 vs. 9.8 months; p = 0.026, log-rank test). Multivariate analysis revealed a significant association between a history of treatment with immune checkpoint inhibitors and the overall survival (hazard ratio, 95% confidence interval: 0.42, 0.20-0.86; p = 0.019, Cox proportional hazards model). A significant interaction was also observed between a history of treatment with an immune checkpoint inhibitor and the tumor histology (p = 0.006), the association between the overall survival and a history of immune checkpoint inhibitor therapy being stronger in the non-small cell lung cancer patients with squamous cell carcinoma than in those with adenocarcinoma. Conclusion: A significant association between history of immune checkpoint inhibitor therapy and the overall survival was detected in elderly NSCLC patients aged ≥70 years old in a clinical practice setting. Our results also suggested that the impact of immune checkpoint inhibitor therapy on the survival differed depending on the tumor histology.

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