scholarly journals Phenotypic Differences in Thyroid Immune Related Adverse Events Following Treatment With Immune Checkpoint Inhibitors

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A876-A877
Author(s):  
Christopher Alan Muir ◽  
Alexander M Menzies ◽  
Roderick John Clifton-Bligh ◽  
Georgina V Long ◽  
Richard A Scolyer ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Thyroid Dysfunction ◽  
Cancer Survival ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Organ Systems ◽  
Euthyroid Hyperthyroxinemia ◽  
Overt Hyperthyroidism

Abstract Background: Thyroid toxicity is common following immune checkpoint inhibitor (ICI) treatment. Published studies estimate the incidence at 10-20%, although rates vary widely between different ICIs. The etiology of ICI-associated thyroid immune related adverse events (irAEs) is unknown & not all patients develop a classic thyroiditis-like presentation of transient hyperthyroidism followed by a hypothyroid phase. Only small observational cohorts have been reported & the clinical & biochemical features of thyroid irAEs have not been well characterized. The current study aimed to describe thyroid irAEs in a large cohort of patients with melanoma. Methods: We reviewed outcomes in a prospective cohort of adult patients undergoing ICI treatment for advanced melanoma. Thyroid function was measured at baseline & at regular intervals during treatment. Thyroid irAEs were defined as new biochemical thyroid dysfunction developing over the course of routine follow-up. Results: Thyroid irAEs occurred in 518 of 1246 (42%) patients. Median follow-up was 11.3 months. Multiple patterns of thyroid-irAEs were observed, such as hyperthyroidism (subclinical or overt) in 31%, hypothyroidism in 8%, & euthyroid hyperthyroxinemia, hypothyroxinemia & isolated low FT3 syndrome each in 1% of participants. Thyroid irAEs were more frequent following combination (CTLA-4 + PD-1) ICI treatment (56%) than following PD-1 (38%) or CTLA-4 (25%) based monotherapies (p=0.001). The severity of thyroid irAEs differed by ICI, with higher rates of overt (vs. subclinical) thyroid dysfunction following combination ICI treatment (47%) relative to PD-1 (37%) & CTLA-4 (19%) monotherapies (p=0.001). Younger age (OR 0.88 per 10-yrs; 95% CI 0.81-0.96), female sex (OR 1.62; 95% CI 1.27-2.08) & combination ICI-treatment (vs. CTLA-4, OR 3.76, 95% CI 2.49-5.75; vs. PD-1, OR 1.90, 95% CI 1.45-2.49) were associated with higher odds of thyroid irAE. Time to onset of thyroid dysfunction was shorter in patients with overt hyperthyroidism relative to other types of thyroid irAE (log rank p=0.001). Overt hyperthyroidism was associated with increased irAEs in other organ systems (colitis, hepatitis, etc), increased irAE severity & increased multi-system irAEs than euthyroid patients or patients with other subtypes of thyroid irAE (p=0.003). Overt hyperthyroidism was also associated with improved progression free survival (HR 0.57; 95% CI 0.39-0.84; p=0.005) & overall survival (HR 0.68; 95% CI 0.49-0.94; p=0.02). No benefit to cancer survival was observed with other thyroid irAE subtypes. Conclusions: Thyroid irAEs were common. Combination ICI treatment resulted in more frequent, more severe, & earlier onset thyroid irAEs. Of thyroid irAE subtypes, overt hyperthyroidism was uniquely associated with increased immune responsiveness, as evidenced by higher incidence of extra-thyroidal irAEs & improvements in cancer survival.

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 Correlation between immune-related adverse events and prognosis in patients with gastric cancer treated with nivolumab

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ken Masuda ◽  
Hirokazu Shoji ◽  
Kengo Nagashima ◽  
Shun Yamamoto ◽  
Masashi Ishikawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Clinical Benefit ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Motor Neuropathy ◽  
Metastatic Sites

Abstract Background Recent studies have shown that immune-related adverse events (irAEs) caused by immune checkpoint inhibitors were associated with clinical benefit in patients with melanoma or lung cancer. In advanced gastric cancer (AGC) patients, there have been few reports about the correlation between irAEs and efficacy of immune checkpoint inhibitors. In this study, we retrospectively investigated the correlation between irAEs and efficacy in AGC patients treated with nivolumab. Methods The subjects of this study were AGC patients received nivolumab monotherapy between January 2015 and August 2018. IrAEs were defined as those AEs having a potential immunological basis that required close follow-up, or immunosuppressive therapy and/or endocrine therapy. We divided the patients who received nivolumab into two groups based on occurrence of irAEs; those with irAEs (irAE group) or those without (non-irAE group). We assessed the efficacy in both groups. Results Of the 65 AGC patients that received nivolumab monotherapy, 14 developed irAEs. The median time to onset of irAEs was 30.5 days (range 3–407 days). Median follow-up period for survivors was 32 months (95% CI, 10.8 to 34.5). The median progression-free survival was 7.5 months (95% CI, 3.6 to 11.5) in the irAE group and 1.4 months (95% CI, 1.2 to 1.6) in the non-irAE group (HR = 0.11, p < 0.001). The median overall survival was 16.8 months (95% CI, 4.4 to not reached) in the irAE group and 3.2 months (95% CI, 2.2 to 4.1) in the non-irAE group (HR = 0.17, p < 0.001). Multivariate analysis demonstrated that number of metastatic sites ≥2 (HR = 2.15; 95% CI, 1.02 to 4.54), high ALP level (HR = 2.50; 95% CI, 1.27 to 4.54), and absence of irAEs (HR = 9.54, 95% CI, 3.34 to 27.30 for yes vs. no) were associated with a poor prognosis. The most frequent irAEs was diarrhea/colitis (n = 5). Grade 3 adverse events were observed in 6 patients; hyperglycemia (n = 2), diarrhea/colitis (n = 1), adrenal insufficiency (n = 1), aspartate aminotransferase increased (n = 1), peripheral motor neuropathy (n = 1). There were no grade 4 or 5 adverse events related to nivolumab. Conclusions Development of irAEs was associated with clinical benefit for AGC patients receiving nivolumab monotherapy.

Thyroid immune-related adverse events following immune checkpoint inhibitor treatment

2021 ◽  
Author(s):  
Christopher A Muir ◽  
Roderick J Clifton-Bligh ◽  
Georgina V Long ◽  
Richard A Scolyer ◽  
Serigne N Lo ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Thyroid Dysfunction ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Progression Free Survival ◽  
Overt Hypothyroidism ◽  
Female Sex ◽  
Younger Age

Abstract Background Thyroid dysfunction occurs commonly following immune checkpoint inhibition. The etiology of thyroid immune-related adverse events (irAEs) remains unclear and clinical presentation can be variable. This study sought to define thyroid irAEs following immune checkpoint inhibitor (ICI) treatment and describe their clinical and biochemical associations. Methods We performed a retrospective cohort study of thyroid dysfunction in patients with melanoma undergoing CTLA-4 and/or PD-1 based ICI treatment from Nov 1, 2009 to Dec 31, 2019. Thyroid function was measured at baseline and at regular intervals following the start of ICI-treatment. Clinical and biochemical features were evaluated for associations with ICI-associated thyroid irAEs. The prevalence of thyroid autoantibodies and the effect of thyroid irAEs on survival were analysed. Results A total of 1246 patients were included with a median follow-up of 11.3 months. 518 (42%) patients developed an ICI-associated thyroid irAE. Subclinical thyrotoxicosis (n=234) was the most common thyroid irAE, followed by overt thyrotoxicosis (n=154), subclinical hypothyroidism (n=61), and overt hypothyroidism (n=39). Onset of overt thyrotoxicosis occurred a median of 5 weeks (IQR 2-8) after receipt of first dose of ICI. Combination immunotherapy was strongly associated with development of overt thyrotoxicosis (OR 10.8, 95% CI 4.51-25.6 vs. CTLA-4 monotherapy; p&lt;0.001), as was female sex (OR 2.02, 95% CI 1.37-2.95; p&lt;0.001) and younger age (OR 0.83 per 10-years, 95% CI 0.72-0.95; p=0.007). By comparison, median onset of overt hypothyroidism was 14 weeks (IQR 8-25). The frequency of overt hypothyroidism did not differ between different ICI-types. The strongest associations for hypothyroidism were higher baseline TSH (OR 2.33 per mIU/L, 95% CI 1.61-3.33; p&lt;0.001) and female sex (OR 3.31, 95% CI 1.67-6.56; p=0.01). Overt thyrotoxicosis was associated with longer progression free survival (HR 0.68, 95% CI 0.49-0.94; p=0.02) and overall survival (HR 0.57, 95% CI 0.39-0.84; p=0.005). There was no association between hypothyroidism and cancer outcomes. Conclusions Thyroid irAEs are common and there are multiple distinct phenotypes. Different thyroid irAE subtypes have unique clinical and biochemical associations, suggesting potentially distinct etiologies for thyrotoxicosis and hypothyroidism arising in this context.

Correlation between immune-related adverse events and prognosis in patients with gastric cancer treated with nivolumab.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4049-4049 ◽  
Author(s):  
Ken Masuda ◽  
Hirokazu Shoji ◽  
Kengo Nagashima ◽  
Shun Yamamoto ◽  
Masashi Ishikawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Clinical Benefit ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Motor Neuropathy ◽  
Progression Of Disease

4049 Background: Recent studies have shown that immune-related adverse events (irAEs) caused by immune checkpoint inhibitors were associated with clinical benefit in patients with melanoma or lung cancer. In advanced gastric cancer (AGC) patients, there have been few reports about the correlation between irAEs and efficacy of immune checkpoint inhibitors. Therefore, in this study, we retrospectively investigated the correlation between irAEs and efficacy in AGC patients treated with nivolumab. Methods: The subjects of this study were AGC patients that had received nivolumab monotherapy between January 2015 and August 2018. IrAEs were defined as those AEs having a potential immunological basis that required close follow-up, or immunosuppressive therapy and/or endocrine therapy. We divided the patients who received nivolumab into two groups based on occurrence of irAEs; those with irAEs (irAE group) or those without (non-irAE group). We assessed the efficacy in both groups. Results: Of the 65 AGC patients that received nivolumab monotherapy, 14 developed irAEs. The median time to onset of irAEs was 30.5 days (range 3–407 days). Median follow-up period for survivors was 32 months (95% CI, 10.8 to 34.5). The median progression-free survival was 7.5 months (95% CI, 3.6 to 11.5) in the irAE group and 1.4 months (95% CI, 1.2 to 1.6) in the non-irAE group (HR = 0.11, p < 0.001). The median overall survival was 16.8 months (95% CI, 4.4 to not reached) in the irAE group and 3.2 months (95% CI, 2.2 to 4.1) in the non-irAE group (HR = 0.17, p < 0.001). Multivariate analysis demonstrated that high ALP level (HR = 2.88; 95% CI, 1.51 to 5.51) and absence of irAEs (HR = 3.06, 95% CI, 3.06 to 23.46 for yes vs. no) were associated with a poor prognosis. The most frequent irAEs was diarrhea/colitis (n = 5). Grade 3 adverse events were observed in 6 patients; hyperglycemia (n = 2), diarrhea/colitis (n = 1), adrenal insufficiency (n = 1), increased aspartate aminotransferase increased (n = 1), peripheral motor neuropathy (n = 1). One of the 14 patients experienced the irAE after discontinuation of nivolumab due to progression of disease. There were no grade 4 or 5 adverse events related to nivolumab. Conclusions: Development of irAEs was associated with clinical benefit for AGC patients receiving nivolumab monotherapy.

scholarly journals Association between Immune Related Adverse Events and Outcome in Patients with Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 860
Author(s):  
Agnese Paderi ◽  
Roberta Giorgione ◽  
Elisa Giommoni ◽  
Marinella Micol Mela ◽  
Virginia Rossi ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Thyroid Dysfunction ◽  
Checkpoint Inhibitors ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Favorable Clinical Outcome

Background: It has been reported that the occurrence of immune-related adverse events (irAEs) in oncological patients treated with immune-checkpoint inhibitors (ICIs) may be associated with favorable clinical outcome. We reported the clinical correlation between irAEs and the efficacy of ICIs in a real-world cohort of metastatic renal cell cancer (mRCC) patients. Methods: We retrospectively evaluated 43 patients with mRCC who were treated with nivolumab or with nivolumab plus ipilimumab. We considered seven specific classes of irAEs including pulmonary, hepatic, gastrointestinal, cutaneous, endocrine, rheumatological, and renal manifestations. We assessed progression-free survival (PFS) of specific irAEs classes compared to the no-irAEs group. Results: Twenty-nine out of 43 patients (67.4%) experienced a total of 49 irAEs registered. The most frequent irAE was thyroid dysfunction (n = 14). The median PFS after the beginning of therapy was significantly longer in patients with thyroid dysfunction and cutaneous reactions. In multivariate analysis, thyroid dysfunction was an independent factor for favorable outcome [HR: 0.29 (95% CI 0.11–0.77) p = 0.013]. Moreover, experiencing ≥2 irAEs in the same patient correlated in multivariate analysis with better outcome compared with none/one irAE [HR: 0.33 (95% CI 0.13–0.84) p = 0.020]. Conclusions: This retrospective study suggests an association between specific irAES (thyroid dysfunction and skin reaction) and efficacy of ICIs in metastatic RCC. Notably, multiple irAEs in a single patient were associated with better tumor response.

scholarly journals Immune-related adverse events of immune checkpoint inhibitors: a brief review

2018 ◽  
Vol 25 (5) ◽  
Author(s):  
G. Myers
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Health Care Professionals ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Hematologic Malignancies ◽  
T Cell Response ◽  
Proactive Management ◽  
Organ Systems

Immune checkpoint inhibitors (icis) such as inhibitors of ctla-4, PD-1, and PD-L1, given as monotherapy or combination therapy have emerged as effective treatment options for immune-sensitive solid tumours and hematologic malignancies. The benefits of icis can be offset by immune-related adverse events (iraes) that leave all organ systems vulnerable and subsequently increase the risk for morbidity and mortality.Because of fluctuating onset and prolonged duration, the toxicities associated with iraes represent a shift from the understanding of conventional anticancer toxicities. The ctla-4 and PD-1/PD-L1 inhibitors modulate T-cell response differently, resulting in distinct toxicity patterns, toxicity kinetics, and dose–toxicity relationships. Using individualized patient education, screening, and assessment for the early identification of iraes is key to proactive management and is therefore key to improving outcomes and prolonging therapy.Management of iraes is guided by appropriate grading, which sets the stage for the treatment setting (outpatient vs. inpatient), ici treatment course (delay vs. discontinuation), supportive care, corticosteroid use, organ specialist consultation, and additional immunosuppression. Health care professionals in oncology must work collaboratively with emergency and community colleagues to facilitate an understanding of iraes in an effort to optimize seamless care.

scholarly journals Promising Immunotherapy in Metastatic Testicular Sex Cord Stromal Tumours After First-Line Chemotherapy

2022 ◽  
Vol 12 ◽  
Author(s):  
Bingqing Shang ◽  
Chuanzhen Cao ◽  
Weixing Jiang ◽  
Hongzhe Shi ◽  
Xingang Bi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Chemotherapy Resistance ◽  
Progression Free Survival ◽  
Retroperitoneal Lymph Node Dissection ◽  
First Line ◽  
Experienced Grade ◽  
Line Chemotherapy

BackgroundTesticular sex cord stromal tumours (TSCSTs) are rare, with few studies focusing on the metastatic TSCST prognosis. The value of treatments, including radical orchiectomy (RO) and retroperitoneal lymph node dissection (RPLND), in preventing metastasis is controversial. Additionally, metastatic TSCSTs are resistant to chemotherapy. We aimed to assess the effectiveness and safety of immunotherapy in metastatic TSCSTs after first-line chemotherapy.MethodsWe retrospectively screened patients with testicular tumours undergoing testis surgery between January 2005 and January 2019. Patients with TSCSTs who had undergone testis-sparing surgery (TSS) or RO were identified. The malignant type was defined as metastasis confirmed by pathology. Treatment responses, progression-free survival (PFS), overall survival (OS) and safety were analysed.ResultsAmong the 494 testicular tumour patients who received TSS or RO, 11 (2.2%) patients with histologically proven TSCSTs were identified. At the last follow-up, 7 patients survived without tumours, and 4 patients developed metastasis and received first-line cisplatin-based chemotherapy, with 1 of them achieving an objective response. Their PFS times were 1.5, 2.2, 9.0, and 17.0 months, respectively. Two patients received immune checkpoint inhibitors (ICIs) after developing chemotherapy resistance and achieved a partial response up to the last follow-up; one of them experienced Grade 1 adverse events, and the other experienced Grade 2 adverse events during immunotherapy. The median OS time of the 4 patients with metastatic TSCSTs was 32 months.ConclusionsTSCSTs are rare, and most are benign with a good prognosis. ICIs represent a promising option for improving clinical outcomes in metastatic TSCSTs.

Abstract 14600: Pre-existing Autoimmune Disease and the Risk for Cardiovascular and Non-cardiovascular Immune Mediated Adverse Events With Immune Checkpoint Inhibitors

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Charlotte Lee ◽  
Zsofia D Drobni ◽  
Amna Zafar ◽  
Raza M Alvi ◽  
Sean P Murphy ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Autoimmune Disease ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Cardiovascular Events ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Skin Toxicity ◽  
Significant Difference

Introduction: The use of immune checkpoint inhibitors (ICIs) is associated with an increase in cardiovascular events. The mechanism is likely related to immune activation and inflammation. Patients with pre-existing autoimmune disease have a baseline increased risk for cardiovascular disease and have been traditionally excluded from clinical trials of ICIs. There is limited data on the cardiovascular and non-cardiovascular safety of ICIs in these patients. Methods: This was a retrospective study of 2845 patients treated with an ICI at the Massachusetts General Hospital. This cohort was screened by individual chart review for patients with a diagnosis of an autoimmune disease prior to ICI therapy. These autoimmune patients were compared to controls at a 1:2 ratio. Baseline characteristics and risk of cardiovascular and non-cardiovascular immune related adverse events (iRAEs) were compared. Cardiovascular events were a composite of myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), stroke, transient ischemic attack (TIA), deep venous thrombosis (DVT), pulmonary embolism (PE), or myocarditis. Results: 93 patients had a diagnosis of an autoimmune disease prior to ICI. These patients were more likely to be older and to have a history of coronary artery disease, heart failure, chronic kidney disease, hypertension and diabetes mellitus. There were 12 events over a median follow-up period of 300 days. There was no significant difference in composite of cardiovascular events in follow-up (13 vs. 9.1%, autoimmune vs. none, P =0.41). The individual cardiovascular event rates were as follows: MI (4.3 vs. 0.5%, P =0.04), PCI (0 vs. 0.5%, P =1), CABG (0. vs. 0.5%, P =1), stroke (0 vs. 0%), TIA (0 vs. 0.5%, P =1), DVT (5.4 vs. 2.2%, P =0.17), PE (1.1 vs. 4.8%, P =0.17), and myocarditis (2.2 vs. 1.1%, P =0.60). There was an increased rate of pneumonitis (14 vs. 4%, P <0.001) and skin toxicity (16 vs. 0%, P <0.001). Conclusions: Patients with pre-existing autoimmune disease treated with an ICI had a higher baseline cardiovascular risk but did not have a significant increase in cardiovascular events in an unadjusted analysis. These patients did, however, have an increased rate of pneumonitis and skin toxicity after ICI.

Behcet’s-like syndrome following pembrolizumab: An immune-related adverse event associated with programmed death receptor-1 inhibitor therapy

2019 ◽  
Vol 26 (4) ◽  
pp. 995-999 ◽  
Author(s):  
Steffi Thomas ◽  
Chay Bae ◽  
Tabanor Joy-Ann ◽  
William Traverse
Keyword(s):  
Adverse Events ◽  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Programmed Death ◽  
Organ Systems ◽  
Wide Range ◽  
The Right

Introduction The landscape for the treatment of metastatic melanoma has been revolutionized with the introduction immune checkpoint inhibitors. Immune checkpoint inhibitors have now become the standard of care for the treatment of cancers. These immune agents including programmed death receptor-1 inhibitors, programmed death-ligand 1 inhibitors and cytotoxic T-lymphocyte antigen-4 inhibitors have shown promising results but have been associated with numerous immune-related complications. Pembrolizumab, a programmed death receptor-1 inhibitor, has been associated with a number of immune-related adverse events affecting multiple organ systems including integument, ocular, endocrine, cardiovascular, pulmonary, renal, gastrointestinal, and musculoskeletal system. Case report We present a case of an 88-year-old Caucasian male with metastatic melanoma of the face with metastasis to the right fifth cranial nerve and into the right cavernous sinus. He underwent resection of the melanoma and was placed on pembrolizumab at 2 mg/kg every three weeks. Interestingly, 24 months on pembrolizumab therapy, he developed corneal erosions, oral and genital ulcerations. Management and outcome Patient completed his 24 months of pembrolizumab and was started on prednisone and colchicine with improvement in his symptoms. At his follow-up eight months, he had recurrence of an oral ulcer. Discussion Here we present a rare case of an elderly male on pembrolizumab who suffered from corneal erosions, oral and genital ulcers, a syndrome similar to Behcet’s disease. Given that pembrolizumab and other immune checkpoint inhibitors are being utilized in the treatment of cancers, physicians should be aware of the wide range immune-related adverse events including the possible Behcet’s-like syndrome presentation.

Implementation of a pharmacy consult service for evaluation of immune checkpoint inhibitor related adverse events at a large community hospital

2020 ◽  
pp. 107815522097026
Author(s):  
Jeff Kamta ◽  
Bren Magruder ◽  
Lisa Hymel
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Primary Outcome ◽  
Checkpoint Inhibitors ◽  
Delayed Presentation ◽  
Consult Service ◽  
Organ Systems ◽  
History Of ◽  
Secondary Outcomes

Introduction Immune checkpoint inhibitors (ICI) are novel oncolytic therapies associated with various immune related adverse events (irAEs) affecting multiple organ systems, which may have a delayed presentation. Identification of irAEs and prompt initiation of appropriate treatment represents a challenge to clinicians. The purpose of this study was to evaluate the effectiveness of a pharmacy consult service in identification and management of irAEs. Methodology: This was a single center, retrospective study. Patients included were: ≥18 years old, admitted as inpatients, and reported a history of cancer treatment within the last year. A pharmacy consult was developed and implemented for patients who reported a history of ICI therapy within the last year. Education regarding the consult service was provided to select physicians, nurses, and all pharmacists. Primary outcome: percent of admitted patients reporting ICI therapy within the last year, who required pharmacist intervention for an irAE. Secondary outcomes: types of interventions performed, percentage of recommendation acceptance, pharmacist time spent. Results Fifty-one patients received a pharmacy immunotherapy consult. Seventeen patients (33%) met the primary outcome. Thirty-three separate recommendations were made by pharmacists for these 17 patients. The secondary outcomes of interventions made and percentage accepted (n; % accepted): Initiation/adjustment of steroid therapy (20; 40%), placement of a consult for oncology or other specialist (10; 70%), other therapeutic interventions (3; 67%). Average time spent by pharmacist on initial consultations (SD): 29 minutes (15). Conclusion A pharmacy consult service may help to increase identification of patients receiving immune checkpoint inhibitors and initiate timely interventions.

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