Rare case of life-threatening thrombocytopenia occurring after radiotherapy in a patient treated with immune checkpoint inhibitor

2020 ◽  
Vol 13 (6) ◽  
pp. e235249 ◽  
Author(s):  
Aurore Hendrix ◽  
Anne-Emmanuella Yeo ◽  
Sarah Lejeune ◽  
Emmanuel Seront
Keyword(s):  
Renal Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Potential Interaction ◽  
High Dose ◽  
Severe Thrombocytopenia ◽  
Metastatic Renal Cancer ◽  
Advanced Renal Cancer ◽  
Endocrine Organs ◽  
Life Threatening

Immune checkpoint inhibitors (ICIs) improve significantly outcome of patients with advanced renal cancer. Although immune-related adverse events involve frequently skin, digestive tract, lung, liver and endocrine organs, haematological toxicities are rare. We describe the case of a patient with metastatic renal cancer who was treated with nivolumab. Eight courses of nivolumab were administered without any toxicity; brain metastases were then diagnosed and treated with stereotactic radiotherapy. As the extra-cranial disease was stable, the ninth course of nivolumab was administered 5 days after the end of radiotherapy. One week later, he presented with rectal and nasal bleeding in a context of severe thrombocytopenia (1000/mm3). High dose of steroids and intravenous immunoglobulin reversed slowly the thrombocytopenia. This case highlights the possibility of life-threatening thrombocytopenia with ICIs. Interestingly, the close time relation with radiotherapy highlights a potential interaction, warranting a close follow-up of patients in this situation.

scholarly journals The Year in Review for Renal Cancer

2020 ◽  
Vol 7 (1) ◽  
pp. 5-6
Author(s):  
Ulka Vaishampayan
Keyword(s):  
Renal Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Front Line ◽  
Advanced Renal Cancer ◽  
Fda Approval ◽  
Multiple Biomarkers ◽  
Line Setting

The treatment of kidney cancer has made some remarkable strides over the last few years. Two regimens received Food and Drug Administration (FDA) approval, multiple biomarkers were reported to show promise, and further enhancement and refinement of the prognostic characteristics occurred. The combinations of anti-angiogenic tyrosine kinase inhibitors with immune checkpoint inhibitors have rap-idly become the preferred therapies in the front-line setting of advanced renal cancer.

Hypophysitis due to Immune Checkpoint Inhibitors

2021 ◽  
Vol 5 (1) ◽  
pp. 01-07
Author(s):  
Sami Azar
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Anterior Pituitary ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Pituitary Hormones ◽  
High Dose ◽  
Antineoplastic Drugs ◽  
Secondary Adrenal Insufficiency ◽  
Life Threatening

Immune checkpoint inhibitors are antineoplastic drugs associated with adverse events that result from unleashing the immune system against self-antigens while attacking neoplastic cells. Endocrinopathies are among the most common associated adverse events and hypophysitis is a frequent endocrine side effect of this treatment. We conducted a systematic search of the literature in 2 databases: PubMed and Medline. Articles that reported endocrine adverse events of immune checkpoint inhibitors were reviewed. Hypophysitis is most commonly seen with cytotoxic T-lymphocytes associated protein 4 (CTLA-4) inhibitors and can result in different anterior pituitary hormones deficiencies. Monitoring for this complication is of particular interest due to the life-threatening nature of secondary adrenal insufficiency and thyroid dysfunction if not promptly recognized and treated. Hypophysitis is the most common endocrinopathy seen and is usually treated by adequate hormonal replacement. The use of high dose corticosteroids has not been established as a treatment of this endocrine toxicity. Hormonal screening should be a part of baseline laboratory testing of all patients undergoing treatment with immune checkpoint inhibitors.

Cutaneous Adverse Events of Immune Checkpoint Inhibitors: A Summarized Overview

2019 ◽  
Vol 14 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Kerasia-Maria Plachouri ◽  
Eleftheria Vryzaki ◽  
Sophia Georgiou
Keyword(s):  
Side Effects ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Skin Toxicity ◽  
Maculopapular Rash ◽  
Symptomatic Treatment ◽  
Stevens Johnson Syndrome ◽  
Life Threatening ◽  
Skin Side Effects

Background:The introduction of Immune Checkpoint Inhibitors in the recent years has resulted in high response rates and extended survival in patients with metastatic/advanced malignancies. Their mechanism of action is the indirect activation of cytotoxic T-cells through the blockade of inhibitory receptors of immunomodulatory pathways, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1) and its ligand (PD-L1). Despite their impressive therapeutic results, they can also induce immune-related toxicity, affecting various organs, including the skin.Objective:To provide an updated summarized overview of the most common immune-mediated cutaneous side effects and their management.Method:English articles derived from the databases PubMed and SCOPUS and published between 2009 and 2018, were analyzed for this narrative review.Results:The most common adverse cutaneous reactions include maculopapular rash, lichenoid reactions, vitiligo and pruritus, with severity Grade 1 or 2. Less frequent but eventually life-threatening skin side effects, including Stevens-Johnson syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms and Toxic Epidermal necrolysis, have also been reported.Conclusion:Basic knowledge of the Immune-Checkpoint-Inhibitors-induced skin toxicity is necessary in order to recognize these treatment-related complications. The most frequent skin side effects, such as maculopapular rash, vitiligo and pruritus, tend to subside under symptomatic treatment so that permanent discontinuation of therapy is not commonly necessary. In the case of life-threatening side effects, apart from the necessary symptomatic treatment, the immunotherapy should be permanently stopped. Information concerning the management of ICIs-mediated skin toxicity can be obtained from the literature as well as from the Summary of Product Characteristics of each agent.

scholarly journals Immune checkpoint inhibitor combination therapies very frequently induce secondary adrenal insufficiency

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Katsunori Manaka ◽  
Junichiro Sato ◽  
Maki Takeuchi ◽  
Kousuke Watanabe ◽  
Hidenori Kage ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Adrenal Insufficiency ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Delayed Diagnosis ◽  
Secondary Adrenal Insufficiency ◽  
Acth Deficiency ◽  
Life Threatening ◽  
Inhibitor Combination

AbstractImmune checkpoint inhibitors (ICIs) are potent therapeutic options for many types of advanced cancer. The expansion of ICIs use however has led to an increase in immune-related adverse events (irAEs). Secondary adrenal insufficiency (AI) can be life-threatening especially in patients with delayed diagnosis. We retrospectively investigated secondary AI in ICI-treated patients. A total of 373 cancer patients treated with ICIs were included and evaluated. An adrenocorticotropic hormone (ACTH) deficiency was described in 13 patients. Among 24 patients with a combination of nivolumab and ipilimumab therapy, 7 patients (29%) developed secondary AI in a median time of 8 weeks during the combination therapy and 2 of 15 patients (13%) developed isolated ACTH deficiency during maintenance nivolumab monotherapy following the combination therapy. More than half of the patients (4/7) with a combination therapy-induced multiple anterior hormone deficiencies was diagnosed as secondary AI based on regular ACTH and cortisol tests with slight subjective symptoms. Secondary AI can arise frequently and rapidly in cancer patients receiving a combination ICI therapy, and thus we speculate active surveillance of AI using regular ACTH and cortisol tests during the combination therapy might be useful for avoiding life-threatening conditions due to secondary AI.

scholarly journals Refractory constrictive pericarditis caused by an immune checkpoint inhibitor properly managed with infliximab: a case report

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Shohei Moriyama ◽  
Mitsuhiro Fukata ◽  
Ryoma Tatsumoto ◽  
Mihoko Kono
Keyword(s):  
Lung Cancer ◽  
Constrictive Pericarditis ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Rescue Therapy ◽  
Treatment Strategies ◽  
High Dose ◽  
Acute Pericarditis ◽  
Line Therapy ◽  
Steroid Refractory

Abstract Background Immune checkpoint inhibitors (ICIs) can cause cardiac immune-related adverse events (irAEs), including pericarditis. Cardiovascular events related to pericardial irAE are less frequent, but fulminant forms can be fatal. However, the diagnosis and treatment strategies for pericardial irAE have not established. Case summary A 58-year-old man was diagnosed with advanced non-small-cell lung cancer and nivolumab was administered as 5th-line therapy. Eighteen months after the initiation of nivolumab, the patient developed limb oedema and increased body weight. Although a favourable response of the cancer was observed, pericardial thickening and effusion were newly detected. He was diagnosed with irAE pericarditis after excluding other causes of pericarditis. Nivolumab was suspended and a high-dose corticosteroid was initiated. However, right heart failure (RHF) symptoms were exacerbated during the tapering of corticosteroid because acute pericarditis developed to steroid-refractory constrictive pericarditis. To suppress sustained inflammation of the pericardium, infliximab, a tumour necrosis factor-alfa inhibitor, was initiated. After the initiation of infliximab, the corticosteroid dose was tapered without deterioration of RHF. Exacerbation of lung cancer by irAE treatment including infliximab was not observed. Discussion IrAE should be considered when pericarditis develops after the administration of ICI even after a long period from its initiation. Infliximab rescue therapy may be considered as a 2nd-line therapy for steroid-refractory irAE pericarditis even with constrictive physiology.

High-dose Interleukin-2 Can Produce a High Rate of Response and Durable Remissions in Appropriately Selected Patients With Metastatic Renal Cancer

2011 ◽  
Vol 34 (1) ◽  
pp. 107-112 ◽  
Author(s):  
Alaaeldin Shablak ◽  
Kanwal Sikand ◽  
Jonathan H. Shanks ◽  
Fiona Thistlethwaite ◽  
Andrea Spencer-Shaw ◽  
...  
Keyword(s):  
Renal Cancer ◽  
Interleukin 2 ◽  
High Rate ◽  
High Dose ◽  
Metastatic Renal Cancer ◽  
Rate Of Response

Effect of high-dose corticosteroid use on efficacy of immune checkpoint inhibitors in patients with renal cell carcinoma (RCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4583-4583
Author(s):  
Chris Labaki ◽  
Sarah Abou Alaiwi ◽  
Andrew Lachlan Schmidt ◽  
Talal El Zarif ◽  
Ziad Bakouny ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Univariate Analysis ◽  
High Dose ◽  
Line Of Therapy

4583 Background: The use of High-Dose Corticosteroids (HDC) has been linked to poor outcomes in patients with lung cancer treated with immune checkpoint inhibitors (ICIs) (Ricciuti B, JCO, 2019). There is no data on the effect of HDC on renal cell carcinoma patients (RCC) treated with immunotherapy. We hypothesized that HDC use would be associated with worse outcomes in RCC patients receiving ICIs. Methods: This study evaluated a retrospective cohort of patients with RCC at Dana-Farber Cancer Institute in Boston, MA. Clinical information including demographics, IMDC risk score, RCC histology, steroid administration, ICI regimen, line of therapy, time to treatment failure (TTF) and overall survival (OS) were collected. Patients were divided into those receiving HDC (prednisone ≥10 mg or equivalent for ≥ 1 week, HDC group) or not receiving HDC (No-HDC group). HDC administration was evaluated in relation to TTF and OS in a univariate analysis (Log-rank test) and a multivariate analysis (Cox regression). Results: 190 patients with RCC receiving ICIs were included, with a median age of 59 years. HDC were administered to 56 patients and 134 patients received no (N= 116) or only low-dose (N=18) steroids. In the HDC group, 40 patients received steroids for immune-related adverse events, 8 for other cancer-related indications, and 8 for non-oncological indications. There was no difference in TTF between the HDC and No-HDC groups (12-mo TTF rate: 34.8 vs. 32.3%, respectively; log-rank p=0.65). Similarly, there was no difference in OS between the HDC and No-HDC groups (36-mo OS rate: 56.7 vs. 62.4%, respectively; log-rank p=0.97). After adjusting for IMDC risk group, RCC histology, ICI regimen type, and line of therapy, TTF and OS did not differ in the HDC group as compared to No-HDC group (HR=1.14 [95%CI: 0.80-1.62], p=0.44 and HR=1.17 [95%CI: 0.65-2.11], p=0.59, respectively). Conclusions: In this retrospective study of patients with RCC treated with ICIs, administration of high-dose corticosteroids was not associated with worse outcomes.[Table: see text]

scholarly journals Management of pulmonary toxicity associated with immune checkpoint inhibitors

2019 ◽  
Vol 28 (154) ◽  
pp. 190012 ◽  
Author(s):  
Myriam Delaunay ◽  
Grégoire Prévot ◽  
Samia Collot ◽  
Laurent Guilleminault ◽  
Alain Didier ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Pulmonary Toxicity ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
Serious Adverse Events ◽  
Programmed Cell Death 1 ◽  
Life Threatening

Immunotherapy has become a standard of care in oncology, following the recent approvals of cytotoxic T-lymphocyte-associated protein-4 and programmed cell death-1 inhibitors in lung cancer, melanoma, renal cell carcinoma, Hodgkin's lymphoma, bladder, head and neck cancers. Besides their efficacy, these agents also generate specific immune-related adverse events. Due to the increasing prescription of immune-checkpoint inhibitors, the incidence of immune toxicity will continue to rise. The awareness of immune-related adverse events is key to ensuring both diagnosis and management of the possible serious adverse events. Although severe immune-related adverse events remain rare, they can lead to discontinued treatment or to death if they are not forecasted and managed properly. Even if lung toxicity is not the most frequent adverse event, it remains critical as it can be life-threatening. Herein, the main aspects of pulmonary toxicity are reviewed and guidelines are also proposed in order to manage the possible side-effects.

scholarly journals Challenge of immune-mediated adverse reactions in the emergency department

2019 ◽  
Vol 36 (6) ◽  
pp. 369-377 ◽  
Author(s):  
Gregory A Daniels ◽  
Angela D Guerrera ◽  
Donna Katz ◽  
Jayne Viets-Upchurch
Keyword(s):  
Immune System ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Adverse Reactions ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoints ◽  
High Dose ◽  
Clear Understanding ◽  
Immune Mediated ◽  
Multiple Drugs

Multiple drugs of a new class of cancer treatments called immune checkpoint inhibitors, which work by enabling the immune system to attack tumour cells, have been approved for a variety of indications in recent years. Immune checkpoints, such as cytotoxic T-lymphocyte antigen-4 and programmed death-1, are part of the normal immune system and regulate immune activation. Treatment with inhibitors of these checkpoints can significantly improve response rates, progression-free survival and overall survival of patients with cancer; it can also result in adverse reactions that present similarly to other conditions. These immune-mediated adverse reactions (IMARs) are most commonly gastrointestinal, respiratory, endocrine or dermatologic. Although patients’ presentations may appear similar to other types of cancer therapy, the underlying causes, and consequently their management, may differ. Prompt recognition is critical because, with appropriate management, most IMARs resolve and patients can continue receiving immune checkpoint inhibitor treatment. Rarely, these IMARs may be life-threatening and escape detection from the usual evaluations in the emergency environment. Given the unusual spectrum and mechanism of IMARs arising from immune checkpoint inhibitors, emergency departmentED staff require a clear understanding of the evaluation of IMARs to enable them to appropriately assess and treat these patients. Treatment of IMARs, most often with high-dose steroids, differs from chemotherapy-related adverse events and when possible should be coordinated with the treating oncologist. This review summarises the ED presentation and management of IMARs arising from immune checkpoint inhibitors and includes recommendations for tools and resources for ED healthcare professionals.

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