scholarly journals Hematologic Immune-Related Adverse Events from Immune Checkpoint Inhibitors: A Systematic Review of Case-Reports and Case-Series

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3606-3606
Author(s):  
Karthik Gnanapandithan ◽  
Prakash Kharel ◽  
Alyssa Grimshaw ◽  
Smith Giri
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Clinical Presentation ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Treatment Strategies ◽  
Case Series ◽  
Supportive Treatment ◽  
Hematopoietic Growth Factors ◽  
Eligibility Criteria ◽  
Organ Systems

Introduction: Immune checkpoint inhibitors (ICI) have proven to be a significant breakthrough in modern cancer therapy. However, this has come at a cost of immune-related adverse events (irAE) affecting various organ systems. Hematological irAEs including autoimmune hemolytic anemia (AIHA), pure red cell aplasia (PRCA), immune thrombocytopenia (ITP), thrombotic thrombocytopenic purpura (TTP), hemophagocytic lymphohistiocytosis (HLH), aplastic anemia and pancytopenia, are well recognized side effects of ICI. Due to their rarity, existing literature is confined to case reports and series. We conducted a systematic review of all published case reports and series till date to summarize clinical presentation, risk factors, management, and outcomes of patients who develop hematologic irAEs during ICI treatment. Methods: Using free text and controlled vocabulary (MESH and EMTREE terms), we performed a systematic search of the literature using Ovid Embase, Ovid Medline, Pubmed, Scopus, and Web of Science Core Collection. Eligibility criteria included any case report or case series describing at least one hematologic irAEs developing during and likely related to ICI therapy for solid/hematologic malignancy. Two authors independently screened the titles, abstracts, and the full text of the selected papers. Patients who had received at least one FDA approved ICI (PD-1, PDL-1 or CTLA-4 inhibitors), and subsequently developed a decline in one or more of cell lines were included. Data regarding clinical presentation, concomitant other irAEs, treatment and clinical outcomes was extracted using a standardized data extraction form and summarized using descriptive statistics. Results: Of the 19856 articles screened, a total of 59 articles were selected for full-text review, and a total of 54 reports describing 57 cases met our eligibility criteria. The median age at the time of presentation was 63 y(interquartile range (IQR) 51-74) yrs, and 29 (50.9%) were males. PD-1 inhibitors were implicated in 35 (61%), CTLA-4 inhibitors in 14 (25%) and PD1/CTLA4 combination therapy in 7 (12%). The most common malignancies included metastatic melanoma (n=32, 56%) and non-small cell lung cancer (n=16, 28%). Only 8 patients (14%) reported a pre-existing history of autoimmune disease and only 11 (19%) had additional irAES involving other organ systems. AIHA (n=16, 28%), ITP (n=12, 21%) and pancytopenia (n=13, 23%) were the three most common subtypes of hematologic irAEs. Two or more cell lines were affected in 13 patients (23%). Twenty-six (46%) of the irAEs were detected on regular laboratory tests. The median number of cycles prior to the onset of hematologic irAEs was 3 (IQR 2-4). Among treatment strategies, corticosteroids were used in most patients (n=50, 88%). Other treatment modalities employed included Intravenous Immunoglobulin (IVIg) (n=14; 25%), hematopoietic growth factors and other supportive treatment were Treatment strategies were based on the actual irAE and the patient's condition. Corticosteroids, transfusion of blood products, hematopoietic growth factors, and other supportive treatment were primarily employed in most patients. Steroids were used in 50 (88%) patients and intravenous immunoglobulins in 14 (25%). Other immunosuppressants, anti-thymocyte globulins, and plasma exchange were used in select patients. Most of the patients (n=44, 77%) were described as having improved or recovered blood counts with treatment. Only 5 (9%) of these patients were rechallenged with the same or other ICI therapy. Among these, the same hematologic irAE recurred in 2 patients (40%). Cytopenia, as an irAE, was directly responsible for the death of 8 patients (14%). Conclusion: Hematologic irAEs are rare but potentially fatal adverse effect of ICI therapy. Although it can have diverse manifestations, AIHA and ITP are the most common subtypes. Almost half of these patients are clinically silent and detected in routine laboratory evaluation. Most hematologic irAEs appear early during the course of therapy and without pre-existing/concomitant irAEs. Most cases report successful resolution with treatment that commonly include high dose corticosteroids, and successful re-challenge has been reported in a few cases. Disclosures No relevant conflicts of interest to declare.

scholarly journals Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: Case Series and Review of the Literature

2019 ◽  
Vol 12 (1) ◽  
pp. 260-276 ◽  
Author(s):  
Nikhil Agrawal ◽  
Arjun Khunger ◽  
Pankit Vachhani ◽  
Teresa A. Colvin ◽  
Alexander Hattoum ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Troponin I ◽  
Cardiac Toxicity ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Case Series ◽  
Fulminant Myocarditis ◽  
Comprehensive Cancer Center ◽  
Cancer Center

The development of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of patients with advanced stage cancers. However, immune-related adverse events are frequently observed. Cardiac toxicity from ICI therapy can range from asymptomatic troponin-I elevations to conduction abnormalities of the heart and even fulminant myocarditis. Although rare, myocarditis is a potentially fatal adverse effect of ICI therapy. We present a series of five cases of ICI-related cardio-toxicity diagnosed and managed at Roswell Park Comprehensive Cancer Center along with a review of published case reports in the literature. Our series highlights the importance of high clinical suspicion, early diagnosis of myocarditis, and prompt initiation of immunosuppressive therapy.

Safety and Efficacy of Immune Checkpoint Inhibitors in Children and Young Adults with Haematological Malignancies: Review and Future Perspectives

2021 ◽  
Vol 19 ◽  
Author(s):  
Eleni Tsotridou ◽  
Eleni Vasileiou ◽  
Elpis Mantadakis ◽  
Athanasios Tragiannidis
Keyword(s):  
Clinical Trials ◽  
Young Adults ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Safety Data ◽  
Case Series ◽  
Great Promise ◽  
Haematological Malignancies

Despite the marked improvement in overall survival rates of paediatric patients with haematological malignancies that has been achieved during the last decades, there is still a pressing need for novel therapeutic approaches for the subset of patients with relapsed or refractory disease. Immune checkpoint inhibitors aim to induce potent anti-tumour immune responses by targeted blockade of inhibitory receptors and have shown great promise in preclinical models and studies in the adult population. However, paediatric malignancies present unique features and so far, experience with these agents remains limited. In the current review we present an overview of efficacy and safety data from case reports, case series and clinical trials employing the use of immune checkpoint inhibitors in children, adolescents and young adults with haematological malignancies. We also discuss new possibilities involving novel targets and combination treatments and provide a summary of the currently registered clinical trials.

Immune checkpoint inhibitors for advanced or metastatic basal cell carcinoma: how much evidence do we need?

Immunotherapy ◽  
2021 ◽  
Author(s):  
Elissar Moujaess ◽  
Reine Merhy ◽  
Joseph Kattan ◽  
Anne-Sophie Sarkis ◽  
Roland Tomb
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Unmet Need ◽  
Case Series ◽  
Metastatic Basal Cell Carcinoma

Basal cell carcinoma (BCC) is one of the most frequent and most curable tumors at its early stages. BCC rarely metastasizes and its treatment in this setting is still challenging. Hedgehog inhibitors showed an activity in advanced or metastatic disease. However, there is an unmet need for new agents. Immune checkpoint inhibitors have been assessed in melanoma and other cutaneous tumors, and very recently an anti-PD1 was approved for advanced BCC. In this paper, available data are reviewed on experimental and preclinical studies evaluating immunotherapy in BCC, as well as on the clinical evidence supporting the efficacy and safety of immune checkpoint inhibitors for advanced or metastatic BCC based on case reports, case series and clinical trials.

scholarly journals Perspective of Immune Checkpoint Inhibitors in Thymic Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1065
Author(s):  
Kyoichi Kaira ◽  
Hisao Imai ◽  
Hiroshi Kagamu
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Thymic Carcinoma ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Objective Response ◽  
Experimental Studies ◽  
Case Series ◽  
Phase Ii Studies ◽  
Dismal Prognosis

Thymic carcinoma is a rare neoplasm with a dismal prognosis, and there are no established therapeutic regimens for metastatic or recurrent disease. Immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 antibodies, are widely approved in several human cancers, contributing to prolonging survival in thoracic tumors. Thymic carcinoma exhibits histologic properties of squamous cell carcinoma (SQC), and resembles the SQC of the lung. ICIs are not approved in thymic carcinoma. Thus, several clinical trials have been undertaken to demonstrate if they are therapeutically effective for patients with thymic carcinoma. In our review, three prospective phase II studies and several case series were discussed in thymic carcinoma. We found that the objective response rate, disease control rate, and progression-free survival in PD-1 blockade monotherapy were approximately 20%, 73%, and four months, respectively. Two exploratory investigations indicated that PD-L1 within tumor cells exhibits a possibility of the therapeutic prediction of PD-1 blockade in thymic carcinoma. Several case reports, alongside their treatment content, have also been reviewed. The therapeutic efficacy of PD-1 blockade monotherapy is still limited in patients with thymic carcinoma. Future perspectives focus on the therapeutic implication of tyrokinase inhibitors plus ICIs or new experimental agents plus ICIs alongside several ongoing experimental studies.

scholarly journals Current Status and Prospects of Immunotherapy for Gynecologic Melanoma

2021 ◽  
Vol 11 (5) ◽  
pp. 403
Author(s):  
Mayuka Anko ◽  
Yusuke Kobayashi ◽  
Kouji Banno ◽  
Daisuke Aoki
Keyword(s):  
Targeted Therapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Treatment Options ◽  
Case Series ◽  
Current Status ◽  
Kit Mutation

Gynecologic melanomas are rare and have a poor prognosis. Although immunotherapy (immune checkpoint inhibitors) and targeted therapy has greatly improved the systemic treatment of cutaneous melanoma (CM) in recent years, its efficacy in gynecologic melanomas remains uncertain because of the rarity of this malignancy and its scarce literature. This review aimed to evaluate the literature of gynecologic melanomas treated with immunotherapy and targeted therapy through a PubMed search. We identified one study focusing on the overall survival of gynecologic melanomas separately and five case series and nine case reports concentrating on gynecologic melanomas treated with an immune checkpoint inhibitor and/or targeted therapy. Furthermore, the KIT mutation has the highest rate among all mutations in mucosal melanoma types. The KIT inhibitors (Tyrosine kinase inhibitors: TKIs) imatinib and nilotinib could be the treatment options. Moreover, immune checkpoint inhibitors combined with KIT inhibitors may potentially treat cases of resistance to immune checkpoint inhibitors. However, because of the different conditions and a small number of cases, it is difficult to evaluate the efficacy of immunotherapy and targeted therapy for gynecologic melanoma rigorously at this time. Further prospective cohort or randomized trials of gynecologic melanoma alone are needed to assess the treatment with solid evidence.

Thrombosis in Cancer Patients Treated with Hematopoietic Growth Factors - A Meta-Analysis

1996 ◽  
Vol 75 (02) ◽  
pp. 368-371 ◽  
Author(s):  
T Barbul ◽  
G Finazzi ◽  
A Grassi ◽  
R Marchioli
Keyword(s):  
Cancer Patients ◽  
Case Reports ◽  
Meta Analysis ◽  
Case Series ◽  
Hematopoietic Growth Factors ◽  
Patients With Cancer ◽  
Cytotoxic Treatment ◽  
Pertinent Data ◽  
Thrombotic Complications ◽  
Vascular Occlusions

SummaryHematopoietic colony-stimulating factors (CSFs) are largely used in patients with cancer undergoing cytotoxic treatment to accelerate neutrophil recovery and decrease the incidence of febrile neutropenia. Clinical practice guidelines for their use have been recently established (1), taking into account clinical benefit, but also cost and toxicity. Vascular occlusions have been recently reported among the severe reactions associated with the use of CSFs, in anedoctal case reports (2, 3), consecutive case series (4) and randomized clinical trial (5, 6). However, the role of CSFs in the pathogenesis of thrombotic complications is difficult to ascertain, because pertinent data are scanty and widely distributed over a number of heterogenous investigations. We report here a systematic review of relevant articles, with the aims to estimate the prevalence of thrombosis associated with the use of CSFs and to assess if this rate is significantly higher than that observed in cancer patients not receiving CSFs.

scholarly journals Zolpidem for Insomnia: A Double-Edged Sword. A Systematic Literature Review on Zolpidem-Induced Complex Sleep Behaviors

2021 ◽  
pp. 025371762199237
Author(s):  
Niti Mittal ◽  
Rakesh Mittal ◽  
M. C. Gupta
Keyword(s):  
Adverse Reactions ◽  
Case Reports ◽  
Case Series ◽  
Eligibility Criteria ◽  
Study Objective ◽  
Spontaneous Reports ◽  
Cochrane Database ◽  
Sleep Behaviors ◽  
Therapeutic Doses ◽  
Favorable Side Effect Profile

Background: Being a nonbenzodiazepine, zolpidem is believed to have a favorable side-effect profile and is widely prescribed for insomnia. However, in the past few years, numerous neuropsychiatric adverse reactions, particularly complex sleep behaviors (CSBs), have been reported with zolpidem. Objective: To conduct a systematic review of zolpidem-associated CSBs. Data Sources: An electronic search was conducted using MEDLINE, Embase, PubMed, and Cochrane database of systematic reviews to extract relevant articles till July 2020. Study Eligibility Criteria: Any type of literature article (case report, case series, and observational or interventional study) reporting CSBs associated with zolpidem. Results: In this review, we present aggregate summarized data from 148 patients presenting with zolpidem-induced CSBs (79 patients from 23 case reports and 5 case series; 69 patients out of 1454 taking zolpidem [4.7%] from three observational clinical studies). Various types of CSBs associated with zolpidem were reported, most common being sleepwalking/somnambulism and sleep-related eating disorder. On causality assessment, around 88% of cases were found to have a probable association with zolpidem. Limitations: Extraction of data from observational studies and spontaneous reports, due to nonavailability of any randomized controlled trials relevant to the study objective. Conclusion and Implication of Key Findings: Zolpidem-induced CSBs, although not very common, may develop when the drug is used at therapeutic doses for insomnia. Doctors need to be alert to monitor such adverse effects of zolpidem and exercise caution while prescribing it.

scholarly journals Ocular adverse events associated with immune checkpoint inhibitors: a novel multidisciplinary management algorithm

2021 ◽  
Vol 13 ◽  
pp. 175883592199298
Author(s):  
Orthi Shahzad ◽  
Nicola Thompson ◽  
Gerry Clare ◽  
Sarah Welsh ◽  
Erika Damato ◽  
...  
Keyword(s):  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Case Series ◽  
Simple Algorithm ◽  
Cancer Therapeutics ◽  
Management Algorithm ◽  
Ocular Symptoms ◽  
Systemic Corticosteroids ◽  
Permanent Loss

Ocular immune-related adverse events (IrAEs) associated with use of checkpoint inhibitors (CPIs) in cancer therapeutics are relatively rare, occurring in approximately 1% of treated patients. Recognition and early intervention are essential because the degree of tissue damage may be disproportionate to the symptoms, and lack of appropriate treatment risks permanent loss of vision. International guidelines on managing ocular IrAEs provide limited advice only. Importantly, local interventions can be effective and may avoid the need for systemic corticosteroids, thereby permitting the continuation of CPIs. We present a single institution case series of eight affected patients managed by our multidisciplinary team. Consistent with previously published series and case reports, we identified anterior uveitis as the most common ocular IrAE associated with CPIs requiring intervention. Based on our experience, as well as published guidance, we generated a simple algorithm to assist clinicians efficiently manage patients developing ocular symptoms during treatment with CPIs. In addition, we make recommendations for optimising treatment of uveitis and address implications for ongoing CPI therapy.

scholarly journals Clinical Presentation, Management, and Prognosis of Pseudogout in Joint Arthroplasty: A Retrospective Cohort Study

2019 ◽  
Vol 4 (1) ◽  
pp. 20-26 ◽  
Author(s):  
Merit P. George ◽  
Floranne C. Ernste ◽  
Aaron Tande ◽  
Douglas Osmon ◽  
Tad Mabry ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Medical Center ◽  
Case Reports ◽  
Joint Infection ◽  
Case Series ◽  
Calcium Pyrophosphate ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Antibiotic Overuse ◽  
Concomitant Infection

Abstract. Introduction: Calcium pyrophosphate deposition disease (CPPD), or pseudogout, is rare in prosthetic joints, but can mimic prosthetic joint infection (PJI) according to case reports. The purpose of this case series is to describe the demographics, presentation, management, and outcomes of a cohort of these patients seen at our academic medical center.Methods: Patients with post-implant pseudogout, who were evaluated at our medical center between January 1, 2000 and June 30, 2016, were identified from our EHR. Data pertaining to demographics, presentation, management, and outcomes were abstracted, and patients were categorized into two groups based on presence of concomitant infection along with positive CPDD findings in synovial fluid.Results: 22 patients were included. 90.9% of cases involved a TKA. The most common indication for arthroplasty was degenerative joint disease. Only four patients had a history of previous gout or pseudogout, three of which belonged to the group with no evidence of concomitant joint infection. Clinical features for patients without concomitant infection included pain (100%), swelling at the joint (88.9%), redness (33.3%), fever (22.2%), and decreased range of motion (100%). 45.5% of patients received antibiotics prior to joint aspiration (44.4% of patients with negative synovial fluid cultures, 46.2% of patients with concomitant infection).Conclusion: Our study suggests similar clinical presentation between post-implant pseudogout and PJI. Among patients with pseudogout as well as in those with PJI, the first dose of antibiotics should not be given before sampling for synovial culture. Unfortunately, many patients receive antibiotics prior to culture ascertainment, which raises concern for antibiotic overuse.

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.

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