scholarly journals Immune Checkpoint Inhibitors Induced Autoimmune Haemolytic Anemia: Case Series and Literature Review

2021 ◽  
Author(s):  
Yuanqiang Wu ◽  
Shengchi Chen ◽  
Jisheng Li ◽  
Yue Pan ◽  
Chunhong Hu ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Prospective Trial ◽  
Case Series ◽  
Aged Patients ◽  
Red Cell Membrane ◽  
Life Threatening ◽  
Haemolytic Anemia ◽  
Positive Direct

Abstract Immune checkpoint inhibitors (ICIs) have brought a revolution to the anti-cancer treatment, however, they also triger a unique spectrum of immune-related adverse events (irAEs). Among irAEs, haemopoietic AEs are rarely reported and mostly severe or even life-threatening, especially autoimmune haemolytic anemia (AIHA). AIHA is presumed to relate to the abnormal formation of circulating autoantibodies against red cell membrane antigens. It usually cannot be discovered timely because of atypical symptoms. It is diagnosed according to presence of hemolysis evidences such as decrease of haemoglobin, increase of indirect bilirubin and lactate dehydrogenase (LDH), urobilinogen, and positive direct antiglobulin test (DAT). Treatments of AIHA are according to clinical experience and consensus, which have not been verified by prospective trial. Here we investigate previous reported ICIs induced AIHA cases including thirty detailedly documented patients. On the other hand, we report three patients who developed AIHA after three different anti-PD-1 antibodies. Most of them were aged patients with melanoma or NSCLC, developed AIHA by anti-PD-1 antibodies and relived with glucocorticoid. 43.3% of previous cases and all of our observed cases had anemia before ICIs treatment, which reminds us of anemia as a risk factor for ICIs induced AIHA. By screening parameters like complete blood examination, reticulocyte, liver function test or DAT test prior to immunotherapy, doctors could exclude pretreatment haemolytic anemia or be aware of post ICIs AIHA. Thus, it is possible to avoid the potentially life-threatening AIHA, or improve the level of pre-alarm and treatment ability of AIHA.

Autoimmune hypophysitis secondary to therapy with immune checkpoint inhibitors: Four cases describing the clinical heterogeneity of central endocrine dysfunction

2020 ◽  
Vol 26 (7) ◽  
pp. 1774-1779 ◽  
Author(s):  
Amelie Hartmann ◽  
Maria Paparoupa ◽  
Bjoern G Volkmer ◽  
Rainer Rompel ◽  
Andreas Wittig ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Clinical Manifestations ◽  
Case Series ◽  
Autoimmune Hypophysitis ◽  
General Weakness ◽  
Wide Range ◽  
Life Threatening ◽  
Loss Of Appetite

Introduction Immune checkpoint inhibitors are becoming increasingly important in oncology. Immune-related adverse events, including autoimmune hypophysitis, have been reported before. Case report We present a case series of three males and one female, suffering from either malignant melanoma or renal cell carcinoma, who developed hypophysitis under Nivolumab and/or Ipilimumab. A wide range of clinical manifestations from asymptomatic hypophysitis, headache, general weakness, loss of appetite, visual field impairment, and confusion to acute life-threatening Addison crisis was observed. Management and outcome: All patients received corticosteroids. Immune checkpoint inhibitors were discontinued in three cases until resolution of symptoms. Discussion The objective of our report is to raise the awareness of physicians, regarding this rare clinical entity, which may become life-threatening, if not promptly recognized and properly treated.

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 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.

Polyradiculoneuropathy induced by immune checkpoint inhibitors: a case series and review of the literature

2020 ◽  
Author(s):  
Kensuke Okada ◽  
Morinobu Seki ◽  
Hiroshi Yaguchi ◽  
Kenichi Sakuta ◽  
Taiji Mukai ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Review Of The Literature

scholarly journals Angiosarcoma patients treated with immune checkpoint inhibitors: a case series of seven patients from a single institution

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Vaia Florou ◽  
Andrew E. Rosenberg ◽  
Eric Wieder ◽  
Krishna V. Komanduri ◽  
Despina Kolonias ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Single Institution

scholarly journals Case Report: Cardiac Toxicity Associated With Immune Checkpoint Inhibitors

2021 ◽  
Vol 8 ◽  
Author(s):  
Ru Chen ◽  
Ling Peng ◽  
Zhihua Qiu ◽  
Yan Wang ◽  
Fen Wei ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Troponin I ◽  
Systemic Corticosteroid ◽  
Checkpoint Inhibitors ◽  
Cardiac Conduction ◽  
Fulminant Myocarditis ◽  
Cancer Type ◽  
Life Threatening ◽  
The Subject

Immune checkpoint inhibitors (ICIs) have now emerged as a mainstay of treatment for various cancer. Along with the development of ICIs, immune-related adverse effects (irAEs) have been the subject of wide attention. The cardiac irAE, a rare but potentially fatal and fulminant effect, have been reported recently. This article retrospectively reviewed 10 cases from our hospital with cardiac irAEs, with severity ranging from asymptomatic troponin-I elevations to cardiac conduction abnormalities and even fulminant myocarditis. In our series, all the cases were solid tumors and lung cancer was the most frequent cancer type (4,40%). In total, three (30.0%) patients experienced more than one type of life-threatening complication. A systemic corticosteroid was given to nine patients (90.0%). The majority of cases (7, 70%) were performed at an initial dose of 1–2 mg/kg/day. Two (20.0%) patients were admitted to ICU, three (30.0%) patients were put on mechanical ventilation, two (20.0%) patients received the plasma exchange therapy, and one patient was implanted with a pacemaker. Two (20.0%) of the patients succumbed and died, with a median duration of 7.5 days (IQR5.0–10.0) from diagnosis of cardiac irAE to death. Based on these results, we recommend that clinicians be alert to cardiac irAEs, including performing cardiovascular examinations before ICI treatment to accurately diagnose suspected myocarditis, enabling immediate initiation of immunosuppressive therapy to improve prognosis.

scholarly journals Multitumor Case Series of Germline BRCA1, BRCA2 and CHEK2-Mutated Patients Responding Favorably on Immune Checkpoint Inhibitors

2021 ◽  
Vol 28 (5) ◽  
pp. 3227-3239
Author(s):  
Lisa Kinget ◽  
Oliver Bechter ◽  
Kevin Punie ◽  
Philip R. Debruyne ◽  
Hilde Brems ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Predictive Biomarkers ◽  
Solid Malignancies ◽  
Tumor Mutational Burden ◽  
Brca1 Brca2 ◽  
Tumor Types ◽  
Selection Of

In recent years, immune checkpoint inhibitors (ICPI) have become widely used for multiple solid malignancies. Reliable predictive biomarkers for selection of patients who would benefit most are lacking. Several tumor types with somatic or germline alterations in genes involved in the DNA damage response (DDR) pathway harbor a higher tumor mutational burden, possibly associated with an increased tumoral neoantigen load. These neoantigens are thought to lead to stronger immune activation and enhanced response to ICPIs. We present a series of seven patients with different malignancies with germline disease-associated variants in DDR genes (BRCA1, BRCA2, CHEK2) responding favorably to ICPIs.

scholarly journals Reintroduction of immune-checkpoint inhibitors after immune-related meningitis: a case series of melanoma patients

2020 ◽  
Vol 8 (2) ◽  
pp. e001034 ◽  
Author(s):  
Stefania Cuzzubbo ◽  
Pauline Tetu ◽  
Sarah Guegan ◽  
Renata Ursu ◽  
Catherine Belin ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Complete Recovery ◽  
Careful Analysis ◽  
Normal Brain ◽  
Retrospective Case ◽  
High Count

Immune-checkpoint inhibitors (ICIs) targeting cytotoxic T lymphocyte-associated antigen-4 and programmed cell death ligand-1) are associated with several immune-related neurological disorders. Cases of meningitis related to ICIs are poorly described in literature and probably underestimated. Several guidelines are available for the acute management of these adverse events, but the safety of resuming ICIs in these patients remains unclear. We conducted a retrospective case series of immune-related meningitis associated with ICIs that occurred between October 1 2015 and October 31 2019 in two centers: Saint-Louis and Cochin hospitals, Paris, France. Diagnosis was defined by a (1) high count of lymphocytes (>8 cells/mm3) and/or high level of proteins (>0.45 g/L) without bacteria/virus or tumor cells detection, in cerebrospinal fluid and (2) normal brain and spine imaging. Patients were followed-up for at least 6 months from the meningitis onset. Seven cases of immune-related meningitis are here reported. Median delay of meningitis occurrence after ICIs onset was 9 days. Steroid treatment was introduced in four patients at a dose of 1 mg/kg (prednisone), allowing a complete recovery within 2 weeks. The other three patients spontaneously improved within 3 weeks. Given the favorable outcome, ICIs were reintroduced in all patients. The rechallenge was well tolerated and no patients experienced meningitis recurrence. In conclusion, in our series, the clinical course was favorable and steroids were not always required. Resuming ICIs in these patients appeared safe and can thus be considered in case of isolated meningitis. However, a careful analysis of the risk/benefit ratio should be done on a case-by-case basis.

Treatment outcomes in malignant pleural mesothelioma: A single center experience of systemic therapies and biomarkers.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20070-e20070
Author(s):  
Adithya Balasubramanian ◽  
Adrian Pick ◽  
Beena Kumar ◽  
Zdenka Prodanovic ◽  
Prashant Joshi ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Survival Data ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Asbestos Exposure ◽  
Case Series ◽  
Stage Iv ◽  
Pleural Mesothelioma ◽  
Retrospective Audit

e20070 Background: Malignant Pleural Mesothelioma (MPM) is a rare but fatal disease related to asbestos exposure, with historic survival in the order of 9 to 17 months. Chemotherapy is associated with only a modest benefit. The advent of immunotherapy has heralded significantly improved outcomes using checkpoint inhibitors in an as yet ill-defined cohort. We aim to identify predictive and prognostic biomarkers in a series of patients (pts) with MPM and describe survival data. Methods: A retrospective audit was undertaken of pts with MPM diagnosed between 2013 and 2017 at a single tertiary centre in Melbourne, Australia (Monash Health). Data relating to patient outcomes and clinicopathological features were obtained through medical reports. Further immunostains are being performed on archived tissue for PDL-1 status. Results: 65 pts were identified, of whom 52 (80.0%) were male. Median age was 73 years (range 44-90). 52 pts were noted to be ECOG 0-1. 42 pts (64.6%) were noted to have suspected asbestos exposure. Epithelioid MPM was the most common subtype, noted in 41 pts (63.1%) (table 1). 8 pts (12.3%) presented with stage IV disease. 16 pts (24.6%) received checkpoint inhibitor therapy, with 10 (63 %) in the second/third line setting. Median overall survival (OS) was 19.8 months (95% CI 13.3-26.3) in the whole cohort.Patient characteristics associated with poor OS were: presence of weight loss (P = 0.001), chest pain (p = 0.08) and ECOG 2 (p = 0.04). Pts with sarcomatoid histology who received immune checkpoint inhibitors in any line of treatment had significantly prolonged OS compared to other histologies. 3-year survival was 80% in this group while median OS was not reached (p = 0.04). This difference was not seen with other histologies. Conclusions: The evolving landscape of treatment in MPM appears to show promise in improving OS. In this unselected case series, our data is consistent with historic controls in terms of survival and prognostic factors. The finding of significantly improved survival with immune checkpoint inhibitors in the sarcomatoid histology is exciting and warrants further exploration. Further data on PDL1 status will be presented.

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