scholarly journals Identification and Classification of Polymyalgia Rheumatica (PMR) and PMR-Like Syndromes Following Immune Checkpoint Inhibitors (ICIs) Therapy: Discussion Points and Grey Areas Emerging from a Systematic Review of Published Literature

Medicines ◽  
2020 ◽  
Vol 7 (11) ◽  
pp. 68
Author(s):  
Ciro Manzo ◽  
Marco Isetta ◽  
Maria Natale ◽  
Alberto Castagna
Keyword(s):  
Clinical Judgment ◽  
Immune Checkpoint ◽  
Polymyalgia Rheumatica ◽  
Immune Checkpoint Inhibitors ◽  
English Language ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Bibliographic Databases ◽  
Future Research ◽  
Free Text

Background: Polymyalgia Rheumatica (PMR) is one of the most frequent rheumatologic immune-related adverse effects (IRAEs) in cancer patients following therapy with immune checkpoint inhibitors (ICIs). Atypical findings in many patients often lead to diagnosing PMR-like syndromes. Materials and methods: The aim of our research was to review reported diagnoses of PMR and PMR-like syndromes following ICIs therapy, and assess whether they can be redefined as adverse drug reaction (ADR). In line with PRISMA guidelines, we carried out a systematic search on three main bibliographic databases, based on a combination of subject headings and free text. We included all studies and case-reports published after 2011 (when FDA approved the use of the first ICI) describing the association of PMR or PMR-like syndromes with all types of ICIs therapy. We excluded reviews, conference abstracts, comments, secondary articles, and non-English language studies. Results: We reviewed data from seven studies and eight case-reports, involving a total of 54 patients. Limitations included: the small size of all studies; only one retrospective study used validated criteria for PMR; most reports assessed IRAEs by clinical judgment only and did not seek validation through assessment scales. To date, it remains a conundrum whether IRAEs-PMR is identical to the idiopathic form of the disease, or whether it should be considered a subset of the disease or a new entity. Conclusions: Our review indicates that the relationship between PMR and ICIs therapy is yet to be clearly understood and defined and that future research should remedy the current limits in study design.

scholarly journals Biomarkers for Predicting Response to Immunotherapy with Immune Checkpoint Inhibitors in Cancer Patients

2019 ◽  
Vol 65 (10) ◽  
pp. 1228-1238 ◽  
Author(s):  
Michael J Duffy ◽  
John Crown
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Future Research ◽  
Specific Gene ◽  
Tumor Type ◽  
Clinical Use ◽  
Durable Response ◽  
Cancer Types

Abstract BACKGROUND Immunotherapy, especially the use of immune checkpoint inhibitors, has revolutionized the management of several different cancer types in recent years. However, for most types of cancer, only a minority of patients experience a durable response. Furthermore, administration of immunotherapy can result in serious adverse reactions. Thus, for the most efficient and effective use of immunotherapy, accurate predictive biomarkers that have undergone analytical and clinical validation are necessary. CONTENT Among the most widely investigated predictive biomarkers for immunotherapy are programmed death-ligand 1 (PD-L1), microsatellite instability/defective mismatch repair (MSI/dMMR), and tumor mutational burden (TMB). MSI/dMMR is approved for clinical use irrespective of the tumor type, whereas PD-L1 is approved only for use in certain cancer types (e.g., for predicting response to first-line pembrolizumab monotherapy in non-small cell lung cancer). Although not yet approved for clinical use, TMB has been shown to predict response to several different forms of immunotherapy and across multiple cancer types. Less widely investigated predictive biomarkers for immunotherapy include tumor-infiltrating CD8+ lymphocytes and specific gene signatures. Despite being widely investigated, assays for MSI/dMMR, PD-L1, and TMB lack standardization and are still evolving. An urgent focus of future research should be the optimization and standardization of method for determining these biomarkers. SUMMARY Biomarkers for predicting response to immunotherapy are paving the way for personalized treatment for patients with diverse cancer types. However, standardization of the available biomarker assays is an urgent requirement.

Malignant melanoma followed by the development of type I diabetes and thyroid dysfunction caused by immune checkpoint inhibitors : Two case reports

Skin Cancer ◽  
2018 ◽  
Vol 33 (1) ◽  
pp. 22-29
Author(s):  
Aya TAKAHASHI ◽  
Masato AMAKATA ◽  
Yoshiki SATO ◽  
Megumi YOKOYAMA ◽  
Kaduhisa HIRAHARA ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Thyroid Dysfunction ◽  
Checkpoint Inhibitors ◽  
Type I Diabetes ◽  
Case Reports ◽  
Type I

Multidisciplinary team management for high grade immune-related adverse events (irAEs): A single center experience.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15076-e15076
Author(s):  
PRABHSIMRANJOT SINGH ◽  
Osama Abu-Shawer ◽  
Amanda Brito ◽  
Eric Yenulevich ◽  
Shilpa Grover ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Massachusetts General Hospital ◽  
Average Length ◽  
Immunosuppressive Agents ◽  
Future Research ◽  
Inpatient Service ◽  
High Grade

e15076 Background: Immune checkpoint inhibitors (ICIs) are increasingly used in the management of cancer. High grade irAEs are uncommon but can be severe and require hospital admission. There is an urgent need for early identification and triage of patients with irAEs in order to improve their management and outcomes. Methods: We established Immunotherapy toxicity (ITOX) team as the first in nation inpatient service at DFCI and Brigham and Women's Hospital (BWH) along with our partners at Massachusetts General Hospital (MGH) that is specifically devoted to mitigating irAEs. The ITOX service is consistent of 2 PAs and a medical oncology attending with an expertise in immunotherapy. The service utilizes algorithms that are modified from the ASCO and NCCN guidelines by our medical subspecialty experts at BWH. The service uses a multi-disciplinary approach with around the hour consulting service from experts in the field including GI, pulmonary, endocrinology and others. We leveraged EPIC to triage patients who are admitted to BWH and have ever received or currently on immune checkpoint inhibitors (ICIs). The daily list generated by EPIC is then curated manually by a PA to identify patients with potential irAEs. Results: A total of 138 patients with high grade irAEs were admitted to BWH between June 2018 and June 2019. Seventy percent of the 201 irAEs- related admissions were to ITOX service (70% accuracy in triaging). Most common irAEs was colitis (31%), pneumonitis (28%) and hepatitis (13%) which is consistent with the most common reported irAEs due to ICIs. Eighty five percent of the patients had grade 3 irAEs and 15% were admitted with life threatening grade 4 adverse events. About half of the patient had received ICI monotherapy; 33% received combination of ICI and non-ICI (chemotherapy or targeted therapy) and 17% received combination of ICIs. Most patients responded to steroids and only 9% had steroid-refractory irAEs requiring other immunosuppressive agents. The average length of stay for irAEs-related admission was 11 days with readmission rate of 26% within a year. Over 50 patients consented for tissue and blood biospecimen collection at the time of toxicity. Conclusions: We demonstrated the feasibility of empowering EMR to accurately triage patients with suspected irAEs to the ITOX service that is supported by institution developed guidelines and specialists. Our model is adaptable in major academic centers and can have major impact on quality improvement and future research studies that can be conducted in this unique setting.

Association of antibiotic exposure with overall survival and colitis in patients with stage III and IV melanoma receiving immune checkpoint inhibitors.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 56-56
Author(s):  
Brian Chu ◽  
Jahan J. Mohiuddin ◽  
Andrea Facciabene ◽  
Xingmei Wang ◽  
Abigail Doucette ◽  
...  
Keyword(s):  
Overall Survival ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Stage Iii ◽  
Secondary Outcome ◽  
Future Research ◽  
Antibiotic Exposure ◽  
Primary Analysis ◽  
Immune Mediated

56 Background: Recent studies suggest that changes in the gut microbiome modulate response to cancer treatment, including immune checkpoint inhibitors (ICI). Broad-spectrum antibiotics (Abx) are known to cause significant dysbiosis. We hypothesize that recent Abx exposure worsens outcomes in patients (pts) with stage III/IV melanoma (MM) receiving ICI. Methods: We identified MM pts treated with ICI from our institutional database. All received their first ICI between 2004-2019. Antibiotic exposure was defined as receipt of Abx within 3 months prior to the first infusion of ICI. The primary outcome was overall survival (OS) and the secondary outcome was immune-mediated colitis requiring intravenous (IV) steroids. Stage III and IV pts were analyzed separately for the primary analysis. Results: Of 568 pts in our database, 20% received Abx within the 3 months prior to ICI. 36% of pts had stage III disease and 26% of pts were treated with either adjuvant or neoadjuvant ICI. 1.6% of pts died of causes other than MM. The Abx+ and Abx- groups were balanced in terms of stage, race, age, sex, BRAF status, LDH, prior systemic therapies, and class of ICI received. Only 4 pts were hospitalized due to the infection prompting the Abx, and no pts died due to the infection. In the Stage IV group, Abx+ pts had worse OS on MV analysis (HR 1.6, 95% CI 1.1-2.2). Stage III Abx+ also had worse OS (HR 2.8, 95% CI 1.3-5.9). In a sensitivity analysis excluding pts who received IV Abx or were admitted due to infection, survival was still worse for Abx+ pts (HR 1.7, 95% CI 1.2-2.4). In a Fine-Grey competing risk MV model, Abx+ had a higher rate of immune-mediated colitis requiring IV steroids (HR 2.1, 95% CI 1.02-4.5). Conclusions: In MM pts treated with ICI, receipt of Abx within 3 months prior to ICI initiation was associated with decreased OS and increased colitis. Future research should include prospective studies to better define the risk/benefit profile of antibiotics in close proximity to ICI. [Table: see text]

scholarly journals Concealed complete response in melanoma patients under therapy with immune checkpoint inhibitors: two case reports

2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Stefan Schliep ◽  
Abbas Agaimy ◽  
Alexander Cavallaro ◽  
Franklin Kiesewetter ◽  
Gerold Schuler ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Complete Response ◽  
Melanoma Patients

scholarly journals Clinical practice alert on the use of immune checkpoint inhibitors in patients latently infected with tuberculosis

2019 ◽  
Author(s):  
Chirag Dhar
Keyword(s):  
Clinical Practice ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Latent Tuberculosis ◽  
Latently Infected ◽  
Multiple Case

Multiple case reports have been published on the risk of tuberculosis activation in patients on immune checkpoint inhibitors (ICPIs). To this matter, I caution clinicians to test for latent tuberculosis before starting their patients on ICPIs.

Re-introducing immunotherapy in patients surviving immune checkpoint inhibitors-mediated myocarditis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15228-e15228
Author(s):  
Shira Peleg Hasson ◽  
Michal laufer-Perl ◽  
Ido Wolf ◽  
Ayelet Sivan
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Single Agent ◽  
Low Grade ◽  
Reduced Ejection Fraction ◽  
Cardiac Symptoms ◽  
The One ◽  
Grade Iii

e15228 Background: Immune checkpoint inhibitors (ICI) have transformed the standard care in cancer treatment. Recent case reports describe ICI-mediated myocarditis with an atypical presentation and fatal potential which lead to permanent interruption of immunotherapy. We aim to characterize ICI-mediated myocarditis and re-introduction to immunotherapy. Methods: We retrospectively evaluated the presentation, severity, and prognosis of patients diagnosed with ICI-mediated myocarditis during 2019, and presented the clinical course and outcomes of patients that were chosen for re-introduction. Results: Among seven patients, only one patient had a history of cardiac disease. The majority were diagnosed with lung adenocarcinoma and treated with anti-programmed death-1 antibody (57%). All patients were treated with single agent ICI. Most patients presented with cardiac symptoms, elevated troponin and typical magnetic resonance imaging; however only 43% had reduced ejection fraction. Five patients were defined as grade I-II and two as grade III-IV. Overall, three patients were chosen for re-introduction with concomitant low dose steroids and weekly troponin follow-up. Two patients diagnosed with grade I/II renewed therapy successfully with no recurrence of symptoms and improvement in disease burden, while the one patient diagnosed with grade III developed worsening of cardiac symptoms after the 1st cycle and therefore therapy was interrupted permanently. Overall, survival was higher among the re-introduction patients (67% vs. 25%). Conclusions: ICI-mediated myocarditis is potentially fatal and leads to permanent interruption of life saving cancer therapy. We imply that re-introduction may be considered in low grade patients; however, better definition of the diagnosis and grading is needed.

Side effects of extended interval dosing of checkpoint inhibitors among patients during COVID-19 pandemic at the Moncton and the Miramichi hospitals.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14550-e14550
Author(s):  
Mahmoud Abdelsalam ◽  
Rana Sughayar ◽  
Glenn Myers ◽  
Mrudula Avileli ◽  
Maged Salem
Keyword(s):  
Lung Cancer ◽  
Side Effects ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Low Dose ◽  
Checkpoint Inhibitors ◽  
Future Research ◽  
Important Data ◽  
Dosing Schedule

e14550 Background: Since the COVID-19 pandemic started, managing cancer patients who are more vulnerable than the rest of the population has been a concern. One of the strategies to decrease cancer patient visits to the Oncology Clinic was by the use of an extended dosing schedule of immune checkpoint inhibitors. The goal of the present study is to record and describe patients’ experiences with irAEs on the modified treatment schedules. Methods: The study included cancer patients getting their treatment at the cancer care clinics at The Moncton Hospital and the Miramichi Hospital, and who switched to receiving either a modified dose of Pembrolizumab or Durvalumab. These participants were asked to complete a short survey that covered important data in their diagnosis and treatment, as well as the type of cancer diagnosed and which drug they were prescribed for treatment. Participants were also asked about the presence of any possible immune-related symptoms from a list of possible AEs since their last treatment visit, and to indicate (A) how often the symptom was experienced, and (B) how severe the symptom was. Results: Twenty-one patients filled out the questionnaire half of whom were females. Most of the patients had lung cancer and were on pembrolizumab. All the patients interviewed developed at least one new symptom after the change in the dose was introduced. The most frequent symptoms reported were itchy skin and fatigue and they were severely experienced. However, very few of the symptoms experienced required a physician consult or hospitalization. Most of the participants welcomed the change in the dose to protect them from COVID-19 and were mainly indifferent as to whether they get the low dose more frequently or the higher dose less frequently. Conclusions: This study has highlighted the frequency and severity of irAEs with the use of extended dosing schedule of immune checkpoint inhibitors. Future research should have more patients to validate this outcome and look for the causes behind the increased incidence and severity of irAEs with higher dose less frequent intervals of these immunotherapies.[Table: see text]

Tamponade during immune checkpoint inhibitors therapy in lung cancer: case-reports and systematic review of the literature

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Mustafic ◽  
A Celebic ◽  
S Lannou ◽  
S Mallet ◽  
A Vieillard Baron ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Smoking Cessation ◽  
Cancer Therapy ◽  
Mortality Rate ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Immune Therapy ◽  
Pericardial Fluid

Abstract Introduction Immune therapy is a new option that has revolutionized cancer therapy. Immune checkpoint inhibitors target mostly either PD-1 (Pembrolizumab, Nivolumab) or PD-L1 (Durvalumab). Immune-related cardiotoxic side effects, among them, tamponade, initially thought to be rare, seem to be increasingly cited in the literature. Moreover, tobacco smoking is linked to 80% of lung cancers. Smoking during cancer therapy may influence on radiotherapy and chemotherapy outcomes but little is known on immunotherapy. Purpose We aimed to review all the published cases of tamponade during immune therapy for lung cancer and to report all the cases that occurred in the University Hospital Ambroise Paré. We also wanted to highlight the possible impact of tobacco on immunotherapy. Methods We conducted a literature review in the PubMED database, from database inception up to 02/14/2020, with a combination of the following terms: “tamponade AND ((immune checkpoint inhibitors) OR (PD-1) OR (PD-L1))”. We also reported all the tamponade cases occurred in our hospital from the beginning of immune checkpoint inhibitors therapy existence up to 02/14/2020. Results Seventeen cases citing tamponade were identified in the literature to which we added 3 cases from our hospital. Mortality rate at 1 month was of 20%. Nivolumab was involved in 80%, Pembrolizumab in 10% and Durvalumab in 10%. In 75%, lung cancer was with a stage IV. Men accounted for 85% and mean age was of 62 years. Active smokers represented 85% and passive smokers existed in 5%, after diagnosis, smoking cessation was done in 10%. Tamponade occurred either shortly after the first administrations but also after several doses. Pericardial fluid cytology revealed malignant cells in half of the cases and microbiology was always negative. For all the cases, excepted for one who was directly considered as palliative, an evacuation of the pericardial fluid was done. In 45% a corticotherapy was initiated. Two cases quickly worsened after pericardial evacuation by unmasking a probable myocarditis with cardiogenic shock which needed the use of a veno-arterial extracorporeal membrane oxygenation. Conclusions Tamponade under immune checkpoint inhibitors therapy appears less rare than initially thought and mortality rate at one month was not negligible. The use of regular echocardiography during this immune therapy may be crucial in detecting early stages of the disease process and smoking cessation should also be advised for these patients. The prevalence of complications among all the patients both exposed to immune therapy and tobacco could not be calculated in this work (case-reports), but some recent studies may indicate survival gains of smoking cessation. Further research establishing more specific guidelines is naturally necessary in dealing with this potentially fatal effect but also in establishing the possibly additional role of smoking in the cardiotoxicity of immunotherapy. Funding Acknowledgement Type of funding source: None

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