scholarly journals SARS-CoV-2 infection and adverse events in patients with cancer receiving immune checkpoint inhibitors: an observational prospective study

2021 ◽  
Vol 9 (2) ◽  
pp. e001694
Author(s):  
Mario Mandala ◽  
Paul Lorigan ◽  
Matilde De Luca ◽  
Andrea Bianchetti ◽  
Barbara Merelli ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Antigen Expression ◽  
Serious Adverse Events ◽  
Exact Test ◽  
Cancer Subtypes ◽  
Patients With Cancer

BackgroundIn ambulatory patients with cancer with asymptomatic or pauci-symptomatic SARS-CoV-2 infection, the safety of targeted therapies (TTs), chemotherapy (CT) or immune checkpoint inhibitors (ICIs) therapy is still unknown.Material and methodsFrom the start of the first epidemic wave of SARS-CoV-2 in Bergamo, Italy, we have prospectively screened all consecutive outpatients who presented for treatment to the Oncology Division of the Papa Giovanni XXIII Hospital, Bergamo for SARS-CoV-2 antigen expression. We identified patients treated with ICIs and compared these to patients with the same cancer subtypes treated with TTs or CT.ResultsBetween March 5 and May 18, 293 consecutive patients (49% melanoma, 34% non-small cell lung cancer, 9% renal cell carcinoma, 8% other) were included in this study: 159 (54%), 50 (17%) and 84 (29%) received ICIs, CT or TTs, respectively. Overall 89 patients (30.0%) were SARS-CoV-2 positive. Mortality of SARS-CoV-2-positive patients was statistically significantly higher compared with SARS-CoV-2 negative patients (8/89 vs 3/204, respectively, Fisher’s exact test p=0.004). All deaths were due to COVID-19. Serious adverse events (SAEs) were more frequent in SARS-CoV-2-positive patients compared with SARS-CoV-2-negative cases (Cochran-Mantel-Haenszel (CMH) test p=0.0008). The incidence of SAEs in SARS-CoV-2 positive compared with SARS-CoV-2 negative patients was similar in ICI and CT patients (17.3% and 3.7% for positive and negative patients in ICIs and 15.4% and 2.7% in CT, Breslow-Day test p=0.891). No COVID-19-related SAEs were observed in the TTs patients.ConclusionsThe incidence of SAEs was higher for SARS-CoV-2-positive patients treated with ICIs and CT, mostly in advanced disease. No SAEs were observed in patients treated with TTs. SAEs were COVID-19 related rather than treatment related. Treatment with ICIs does not appear to significantly increase risk of SAEs compared with CT. This information should be considered when determining treatment options for patients.

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.

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.

Immune-related adverse events associated with immune checkpoint inhibitors in patients with cancer

2020 ◽  
pp. 030089162095346
Author(s):  
Nilay Sengul Samanci ◽  
Duygu Ilke Cikman ◽  
Kerem Oruc ◽  
Sahin Bedir ◽  
Emir Çelik ◽  
...  
Keyword(s):  
Adverse Events ◽  
Health Care Providers ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Early Recognition ◽  
Care Providers ◽  
Patients With Cancer ◽  
Combination Treatments ◽  
Grade 3

Introduction: With the widespread use of immune checkpoint inhibitors (ICIs), we are facing challenges in the management of immune-related adverse events (irAEs). We aimed to characterize the spectrum of toxicity, management, and outcomes for irAEs. Methods: Patients who were treated with at least one ICI in clinical trials, expanded access programs, or routine clinical practice were included. Clinical and laboratory parameters were collected retrospectively to determine the incidence of irAEs, methods of management, and treatment outcomes. Results: A total of 255 patients were screened retrospectively. Of these, 71 (27.8%) patients developed irAEs. More than 2 different types of irAEs were detected in 16 (6.2%) out of 255 patients. A total of 3177 doses were given to 255 patients. In 93 (2.9%) of the 3177 doses, 1 episode of irAEs was experienced. A total of 22 out of 93 (23.7%) episodes were reported as grade 1, 49 (52.7%) as grade 2, 19 (20.4%) as grade 3, and 3 (3.2%) as grade 4. The most frequently seen irAEs were pneumonitis, hepatitis, and hypothyroidism. With regard to treatment, 39 out of 93 episodes (42%) of any grade irAEs occurred after anti–programmed cell death-1 therapy, 47 (50.5%) occurred following administration of anti–programmed death-ligand 1, and 7 (7.5%) occurred after combination treatments. Conclusion: With the increased use of immunotherapeutic agents, increased awareness and early recognition are required for effective management of irAEs. Our experience as a single institution might be of use for health care providers in oncology.

scholarly journals Immuno-related endocrinopathy in patients treated with immune checkpoint inhibitors

2020 ◽  
pp. 16-24
Author(s):  
D. I. Yudin ◽  
K. K. Laktionov ◽  
K. A. Sarantseva ◽  
O. I. Borisova ◽  
V. V. Breder ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Clinical Practice ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Serious Adverse Events ◽  
Immune Mediated ◽  
Discontinuation Of Treatment ◽  
The Russian Federation

Recently immune checkpoint inhibitors amazingly changed the landscape of cancer therapy worldwide. The number of immune checkpoint molecules in clinical practice is constantly increasing. There are some monoclonal antibodies recently registered in the Russian Federation: anti-PD1 antibodies (nivolumab, pembrolizumab), anti-PD-L1 (atezolizumab, durvalumab), anti-CTLA-4 (ipilimumab). Immune-mediated endocrinopathies are some of the most common complications of immunotherapy. According to the results of clinical studies, the incidence of serious endocrine immuno-mediated adverse events with anti-PD1 monoclonal antibodies is low (3.5–8%). The use of anti-CTLA4 antibodies, combined regimens, and the use of immunotherapy after chemoradiotherapy significantly increase the incidence of serious adverse events to 30%. In clinical practice of N.N. Blokhin Cancer Research Center among 245 non-small cell lung cancer and hepatocellular carcinoma patients treated with immunotherapy, 22 (8,9%) developed an immune-mediated endocrinopathy. Most patients developed adverse events of 1–2 degrees, in two patients – 3 degrees, requiring discontinuation of treatment. The aim of this article was to provide useful information and recommendations regarding the management of common immuno-related endocrine adverse events (including hypothyroidism, hyperthyroidism, pituitary, adrenal insufficiency) for clinical oncologists.

scholarly journals Association of Blood Biomarkers and Autoimmunity with Immune Related Adverse Events in Patients with Cancer treated with Immune Checkpoint Inhibitors

2021 ◽  
Author(s):  
Despina Michailidou ◽  
Ali Khaki ◽  
Maria Morelli ◽  
Leonidas Diamantopoulos ◽  
Namrata Singh ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Cancer Type ◽  
Blood Biomarkers ◽  
Lymphocyte Ratio ◽  
Patients With Cancer ◽  
History Of

Abstract Background: Patients with cancer treated with immune checkpoint inhibitors (ICIs) develop immune related adverse events (irAEs), however biomarkers are lacking. We hypothesized that clinicopathologic and laboratory factors would be associated with irAE risk and overall survival (OS) in this population.Methods: In a retrospective study of patients treated with ICIs we collected clinicopathologic, laboratory, irAEs and outcomes data. The association between baseline blood biomarkers, clinicopathologic features and irAEs was assessed by logistic regression adjusting for age, sex, smoking, cancer type, performance status, concomitant other systemic therapy, history of autoimmune disease (AD) and chronic infection. Optimal cutoff values of biomarkers were identified by recursive partitioning analysis.Results: 470 patients were identified; 156 (33%) developed irAEs, which were associated with baseline absolute lymphocyte count >2.6k/ul (adjusted [a]OR:4.12), neutrophil to lymphocyte ratio (NLR) ≤5.3 (aOR:2.08) and monocyte to lymphocyte ratio (MLR)≤0.73 (aOR:3.11). Patients with pre-existing AD (aOR:2.81), family history of AD (aOR:5.86), and ICI combination (aOR:2.26) had higher odds of irAEs. Baseline NLR≤5.3 (aHR:0.68) and MLR≤0.73 (aHR:0.43) were associated with longer OS.Conclusion: irAE were associated with autoimmune history, ICI combination and baseline laboratory measurements. Lower NLR and MLR may have favorable prognostic value. Our hypothesis-generating findings require validation in larger prospective studies.

scholarly journals Evaluation of Readministration of Immune Checkpoint Inhibitors After Immune-Related Adverse Events in Patients With Cancer

JAMA Oncology ◽  
2019 ◽  
Vol 5 (9) ◽  
pp. 1310 ◽  
Author(s):  
Audrey Simonaggio ◽  
Jean Marie Michot ◽  
Anne Laure Voisin ◽  
Jérome Le Pavec ◽  
Michael Collins ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Patients With Cancer

scholarly journals Treatment-Related Serious Adverse Events of Immune Checkpoint Inhibitors in Clinical Trials: A Systematic Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Tao Ouyang ◽  
Yanyan Cao ◽  
Xuefeng Kan ◽  
Lei Chen ◽  
Yanqiao Ren ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
English Language ◽  
Checkpoint Inhibitors ◽  
Serious Adverse Events ◽  
Comprehensive Information ◽  
Grade 3

BackgroundImmune Checkpoint Inhibitors (ICI) have been progressively used in cancer treatment and produced unique toxicity profiles. This systematic review aims to comprehend the patterns and occurrence of treatment-related adverse events (trAEs) based on ICI.MethodsPICOS/PRISMA methods were used to identify published English-language on PubMed, Web of Science, and Scopus from 2015 to 2020. Published clinical trials on ICI monotherapy, combined ICIs, and ICI plus other treatment with tabulated data on grade≥3 trAEs were included. Odds ratio (OR), χ2 tests were used to analyze for effect size and associations.ResultsThis review included 145 clinical trials involving 21786 patients. Grade 3-5 trAEs were more common with ICI when they were plused with other treatments compared with ICI monotherapy(54.3% versus 17.7%, 46.1%, p<0.05). Grade 3-5 trAEs were also more common with CTLA-4 mAbs compared with anti-PD-1 and anti-PD-L1 (34.2% versus 15.1%, 13.6%, p<0.05). Hyperthyroidism (OR 3.8, 95%CI 1.7–8.6), nausea (OR 3.7, 95%CI 2.5–5.3), diarrhea (OR 2.7, 95%CI 2.2–3.2), colitis (OR 3.4, 95%CI 2.7–4.3), ALT increase (OR 4.9, 95%CI 3.9–6.1), AST increase (OR 3.8, 95%CI 3.0–4.9), pruritus (OR 2.4, 95%CI 1.5–3.9), rash (OR 2.8, 95%CI 2.1–3.8), fatigue (OR 2.8, 95%CI 2.2–3.7), decreased appetite (OR 2.4, 95%CI 1.5–3.8), and hypophysitis (OR 2.0, 95%CI 1.2–3.3) were more frequent with combined ICIs. Diarrhea (OR 8.1, 95%CI 6.4–10.3), colitis (OR 12.2, 95%CI 8.7–17.1), ALT increase (OR 5.1, 95%CI 3.5–7.4), AST increase (OR 4.2, 95%CI 2.8–6.3), pruritus (OR 4.1, 95%CI 2.0–8.4), rash (OR 4.4, 95%CI 2.9–6.8), hypophysitis (OR 12.1, 95%CI 6.3–23.4) were more common with CTLA-4 mAbs; whereas pneumonitis (OR 4.7, 95% CI 2.1–10.3) were more frequent with PD-1 mAbs.ConclusionsDifferent immune checkpoint inhibitors are associated with different treatment-related adverse events profiles. A comprehensive data in this systematic review will provide comprehensive information for clinicians.

scholarly journals Hemophagocytic Lymphohistiocytosis Secondary to PD-1 and IDO Inhibition in a Patient with Refractory Glioblastoma

2020 ◽  
Vol 13 (2) ◽  
pp. 508-514
Author(s):  
Rohit Thummalapalli ◽  
Thatcher Heumann ◽  
Julie Stein ◽  
Sarah Khan ◽  
David S. Priemer ◽  
...  
Keyword(s):  
Adverse Events ◽  
Solid Tumors ◽  
Immune Checkpoint ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Altered Mental Status ◽  
Rapid Onset ◽  
History Of

Immune checkpoint inhibition (ICI)-based approaches have transformed the treatment landscape of numerous solid tumors. Glioblastoma (GBM) is an aggressive and almost universally fatal disease which is in need of novel treatment options, and combinations of immune checkpoint inhibitors, including dual agent therapy, are starting to be explored in refractory GBM. Growing adoption of ICI-based approaches in solid tumors has been met with improved understanding of immune-related adverse events (IRAEs), including primary hematologic adverse events. Although management guidelines for multiple hematologic IRAEs have been established, the emergence of hemophagocytic lymphohistiocytosis (HLH) secondary to ICI therapy has only rarely been described, and its pathogenesis and optimal management are incompletely understood. We present the case of a 74-year-old male with a history of refractory GBM treated with PD-1 and indoleamine-pyrrole 2,3-dioxygenase (IDO) inhibition who experienced acute liver injury, followed by progressive fevers, altered mental status, and cytopenias. Serum studies and examination of spleen and bone marrow pathology were consistent with HLH, which was refractory to steroids and ultimately resulted in his rapid clinical decline. Here, we review prior cases of HLH secondary to ICI therapy across solid tumors, and explore potential mechanisms contributing to the rapid onset and refractory nature of our patient’s HLH syndrome. We hope to further highlight HLH as an emerging hematologic IRAE secondary to ICI therapy, and suggest that new practice guidelines begin to recognize HLH as a characteristic hematologic IRAE in patients treated with PD-1 and other immune checkpoint inhibitors.

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