scholarly journals Associated Myocarditis: A Predictive Factor for Response?

2020 ◽  
Vol 13 (2) ◽  
pp. 550-557 ◽  
Author(s):  
Walid Shalata ◽  
Nir Peled ◽  
Itzhak Gabizon ◽  
Omar Abu Saleh ◽  
Waleed Kian ◽  
...  

In the present case report, we aimed to describe 2 cases of myocarditis occurring as serious adverse effects of immune checkpoint inhibitors (ICIs) administered as treatment for metastatic melanoma. We describe 2 female patients: an 81-year-old treated with pembrolizumab and a 55-year-old treated with a combination of nivolumab and ipilimumab. Both patients underwent resection of metastases; while under treatment, both developed myocarditis, most probably as a toxicity from pembrolizumab and nivolumab plus Ipilimumab, respectively. While they achieved complete response, the occurrence of myocarditis as a toxicity of ICIs may have been a predictive sign that the immune system was sufficiently activated by the checkpoint inhibitor therapy to induce complete remission.

2020 ◽  
pp. 107815522094394
Author(s):  
Lukas Delasos ◽  
Christopher Bazewicz ◽  
Aleksandra Sliwinska ◽  
Nerea Lopetegui Lia ◽  
James Vredenburgh

Introduction Immune-checkpoint inhibitors have become an increasingly popular form of systemic therapy for cancer treatment. Their use has proven to be so effective that certain regimens have gained approval as first-line therapy for various solid tumor types. The most common and well-studied forms of immunotherapy include agents that target cytotoxic T-lymphocyte antigen-4, programmed death-1, and programmed death ligand-1. These therapies act by blocking signaling between immune cells and cancer cells which subsequently augment T cell-mediated destruction of tumor cells. Case report Here, we report a case of a 77-year-old black male with no history of or risk factors for diabetes mellitus who presented with acute onset of diabetic ketoacidosis after beginning immunotherapy with nivolumab for metastatic high-grade neuroendocrine tumor of the lung. He was admitted and treated for diabetic ketoacidosis but required prolonged use of an insulin infusion with frequent need of intravenous dextrose due to labile blood sugars. The patient was eventually discharged and discontinued further immunotherapy with nivolumab. Discussion Due to the unique mechanisms by which immune-checkpoint inhibitors cause immune-mediated destruction of tumor cells, clinicians may be challenged with their associated autoimmune complications referred to as immune-related adverse events. In particular, the incidence of endocrine dysfunction following immune-checkpoint inhibitor therapy is approximately 12%, with the development of insulin-dependent diabetes mellitus being a rare complication. Increasing awareness of immune-related adverse events is essential for the early recognition and effective management of patients who present with life-threatening complications related to immune-checkpoint inhibitor therapy.


2020 ◽  
Vol 10 (4) ◽  
pp. 204589402096096 ◽  
Author(s):  
Matthew Glick ◽  
Chase Baxter ◽  
David Lopez ◽  
Kashif Mufti ◽  
Stephen Sawada ◽  
...  

Immune checkpoint inhibitors successfully treat various malignancies by inducing an immune response to tumor cells. However, their use has been associated with a variety of autoimmune disorders, such as diabetes, hepatitis, and pneumonitis. Pulmonary arterial hypertension due to checkpoint inhibitor use has not yet been described. We present a novel case of pulmonary arterial hypertension associated with systemic lupus erythematosus and Sjogren’s syndrome overlap that was induced by therapy with the checkpoint inhibitor durvalumab.


Author(s):  
Hassan Izzedine ◽  
Thibaud Chazal ◽  
Rimda Wanchoo ◽  
Kenar D Jhaveri

Abstract Immune checkpoint inhibitors (CPIs) have recently become a cornerstone for the treatment of different advanced cancers. These drugs have the ability to reactivate the immune system against tumour cells but can also trigger a myriad of side effects, termed immune-related adverse events (irAEs). Although there are numerous reports of CPI-related endocrinopathies, hypercalcaemia as a suspected irAE is not well documented. The mechanisms of CPI hypercalcaemia are not clearly established. However, in our review, four distinct causes emerged: endocrine disease-related, sarcoid-like granuloma, humoral hypercalcaemia due to parathyroid-related hormone and hyperprogressive disease following CPI initiation. Prompt recognition of hypercalcaemia and the institution of therapy can be lifesaving, affording the opportunity to address the underlying aetiology. In this review we discuss the incidence, diagnosis and management of immune-related hypercalcaemia in oncological patients receiving CPI agents.


2018 ◽  
Vol 2 (17) ◽  
pp. 2226-2229 ◽  
Author(s):  
Laura K. Schoch ◽  
Kenneth R. Cooke ◽  
Nina D. Wagner-Johnston ◽  
Ivana Gojo ◽  
Lode J. Swinnen ◽  
...  

Key Points Checkpoint inhibition use before alloBMT followed by PTCy is not associated with increased aGvHD or transplant-related mortality/morbidity. Prior checkpoint inhibitor therapy should not be a contraindication to allogeneic transplantation, especially in the setting of PTCy.


2019 ◽  
Vol 160 (23) ◽  
pp. 887-895
Author(s):  
Éva Szekanecz ◽  
Zoltán Szekanecz

Abstract: Oncotherapy has been revolutionised by the introduction of immune-checkpoint inhibitors including CTLA4, PD1 and PDL1 inhibitors. Patients with malignant diseases may largely benefit from these therapies, which may result in long-term remission even in the most therapy-resistant tumour types. Differences in the mode of action of the various agents may result in varying side-effect profiles. In addition to organ-specific side-effects, overt autoimmune syndromes may also develop. Our current view of oncotherapy has changed as these mostly immune-mediated side-effects highly differ from those observed previously during the administration of traditional anti-tumour compounds. These side-effects should be carefully characterized and differentiated from infections or the progression of the underlying malignancy. Fortunately, several recent recommendations have become available on the management of immune-mediated adverse events due to checkpoint-inhibitor therapy. Orv Hetil. 2019; 160(23): 887–895.


2020 ◽  
Vol 13 (5) ◽  
pp. e233519
Author(s):  
Kevin B Harris ◽  
Pauline Funchain ◽  
Brian B Baggott

As immune checkpoint inhibitors (ICIs) are increasingly used, clinicians are more frequently encountering the side effects of these therapies. ICIs have been implicated in numerous adverse effects against healthy tissues. We present a case of a patient who developed treatment refractory checkpoint inhibitor colitis. Following colonoscopy, it was discovered that this patient had cytomegalovirus (CMV) coinfection. This case report highlights the importance of undertaking an appropriate assessment, including endoscopic and histologic investigation, of patients with presumed ICI colitis. Accurately diagnosing a superimposed CMV colitis changes clinical management and can improve patient outcomes.


2021 ◽  
Author(s):  
Arthur Sillah ◽  
Scott S Tykodi ◽  
Evan T Hall ◽  
John A Thompson ◽  
Nathaniel F Watson ◽  
...  

Lifestyle factors could plausibly modulate the host immune system, the tumor microenvironment and, hence, immune checkpoint inhibitor (ICI) response. As such, these factors should be considered in ICI studies.


2019 ◽  
Vol 25 (8) ◽  
pp. 1867-1872 ◽  
Author(s):  
Jenessa Lee ◽  
Anastasia Graham ◽  
Amy Sion

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.


Blood ◽  
2020 ◽  
Author(s):  
Florian Moik ◽  
Wei-Shin Evelyn Chan ◽  
Sarah Wiedemann ◽  
Christoph Hoeller ◽  
Felix Tuchmann ◽  
...  

The risk of venous and arterial thromboembolism (VTE/ATE) associated with immune checkpoint inhibitors is currently unclear, and clinical trials evaluating these agents in patients with cancer did not provide information. Our aim was to quantify risk of VTE/ATE in a cohort of patients treated with immune checkpoint inhibitors, explore clinical impact, and investigate potential clinical risk factors. Patients treated with an immune checkpoint inhibitor at the Medical University of Vienna from 2015-2018 were identified using the in-house pharmacy records (n=672; most frequent entities: 30.4% melanoma, 24.1% non-small-cell lung cancer; 86% stage-IV-disease). A retrospective chart-review was performed to screen for VTE and/or ATE. Cumulative incidences and between-group differences were analysed within a competing-risk framework. Multi-state modelling was applied to study the impact of VTE/ATE on mortality. Over a median follow-up of 8.5 months, 47 VTE and 9 ATE were observed. Cumulative incidences of VTE and ATE were 12.9% [95% confidence interval (CI): 8.2-18.5)] and 1.8% [95%CI: 0.7-3.6]. Occurrence of VTE was associated with increased mortality (transition hazard-ratio (THR): 3.09 [95%CI: 2.07-4.60]. History of VTE predicted VTE occurrence (subdistribution hazard ratio (SHR): 3.69 [2.00-6.81]) and distant metastasis was non-significantly associated with VTE risk (SHR: 1.71 [95%CI: 0.62-4.73]). No association of VTE with ECOG performance-status, Charlson-Comorbidity-Index or the Khorana-score was observed, and rates of VTE were comparable among subgroups of tumour types and checkpoint-inhibitory agents. In conclusion, patients with cancer under immune checkpoint inhibitor therapy are at high risk of thromboembolism, especially VTE. Furthermore, VTE occurrence was associated with increased risk of mortality.


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