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1.
J Natl Compr Canc Netw ; 20(10): 1134-1138, 2022 10.
Article in English | MEDLINE | ID: covidwho-2080823

ABSTRACT

BACKGROUND: Whether COVID-19 vaccination and the associated immune response increases susceptibility to immune-related adverse events (irAEs) among patients treated with immune checkpoint inhibition (ICI) remains unknown. Short-term follow-up can assess the safety of concurrent administration of the vaccine and ICI treatment. METHODS: We conducted an electronic health record analysis of a cohort of 408 patients with cancer receiving ICI therapy and who were vaccinated for COVID-19 between January 16 and March 27, 2021. Patients were seen in follow-up for 90 days from the day of the first dose in this single-institution tertiary care center. We evaluated the incidence of irAEs and the frequency of each event type and grade among patients who experienced an irAE. We also evaluated the incidence of irAEs in patients who began a new immunotherapy agent after vaccination. RESULTS: Among 408 patients with cancer receiving ICI therapy (median age, 71 years; 217 [53%] male), administration of a COVID-19 mRNA vaccine within 90 days of ICI treatment was not associated with an increased incidence of irAEs. A total of 27 (7%) patients experienced a new irAE within the observation period. Among patients with previous irAEs from ICIs (n=54), 3 (6%) experienced a recurrent irAE, and of those initiating a new immunotherapy (n=52), 9 (17%) experienced an irAE. No excess risk of COVID-19 diagnosis was seen in this subset of patients receiving ICI therapy, and no breakthrough COVID-19 cases were seen after full COVID-19 vaccination. CONCLUSIONS: These findings should reassure providers that COVID-19 vaccination during ICI therapy is safe and efficacious.


Subject(s)
COVID-19 , Neoplasms , Aged , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Testing , COVID-19 Vaccines/adverse effects , Female , Humans , Immune Checkpoint Inhibitors/adverse effects , Male , Neoplasms/complications , Neoplasms/drug therapy , Retrospective Studies , Vaccines, Synthetic , mRNA Vaccines
2.
Future Oncol ; 18(10): 1185-1198, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-2065335

ABSTRACT

Cabozantinib inhibits multiple receptor tyrosine kinases, including the TAM kinase family, and may enhance response to immune checkpoint inhibitors. One cohort of the ongoing phase Ib COSMIC-021 study (NCT03170960) evaluating cabozantinib plus the PD-L1 inhibitor atezolizumab in men with metastatic castration-resistant prostate cancer (mCRPC) that has progressed in soft tissue on/after enzalutamide and/or abiraterone treatment for metastatic disease has shown promising efficacy. Here, we describe the rationale and design of a phase III trial of cabozantinib plus atezolizumab versus a second novel hormone therapy (NHT) in patients who have previously received an NHT for mCRPC, metastatic castration-sensitive PC or nonmetastatic CRPC and have measurable visceral disease and/or extrapelvic adenopathy - a population with a significant unmet need for treatment options. Trial Registration Clinical Trial Registration: NCT04446117 (ClinicalTrials.gov) Registered on 24 June 2020.


Subject(s)
Adenocarcinoma/drug therapy , Anilides/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Immune Checkpoint Inhibitors/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy , Pyridines/therapeutic use , Adenocarcinoma/pathology , Androstenes/therapeutic use , Benzamides/therapeutic use , Humans , Male , Neoplasm Metastasis , Nitriles/therapeutic use , Phenylthiohydantoin/therapeutic use , Prostatic Neoplasms, Castration-Resistant/pathology , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors
3.
J Int Med Res ; 50(9): 3000605221125047, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2053626

ABSTRACT

Lung cancer, considered one of the most common causes of cancer deaths worldwide, is a complex disease with its own challenges. The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), compounded these challenges and forced the medical healthcare system to alter its approach to lung cancer. This narrative review aims to identify the effect of the COVID-19 pandemic on lung cancer screening, diagnosis and management. During this public health crisis, various medical societies have worked on developing guidelines to protect patients with lung cancer from the deleterious effects of SARS-CoV-2 infection, as well as from the complications imposed by treatment delays. The different therapeutic approaches, such as surgery, radiation oncology and immune checkpoint inhibitor therapy, along with the latest international recommendations, will be discussed. Protecting patients with lung cancer from COVID-19 complications, while avoiding barriers in treatment delays, has brought unique challenges to healthcare facilities. Prompt modifications to guidelines, and constant evaluation of their efficacy, are thus needed.


Subject(s)
COVID-19 , Lung Neoplasms , COVID-19 Testing , Early Detection of Cancer , Humans , Immune Checkpoint Inhibitors , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Lung Neoplasms/therapy , Pandemics/prevention & control , SARS-CoV-2
4.
Eur Urol ; 82(6): 602-610, 2022 12.
Article in English | MEDLINE | ID: covidwho-2049204

ABSTRACT

BACKGROUND: Intravenous immune checkpoint inhibition is an effective anticancer strategy for bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) but may be associated with greater systemic toxicity compared with localized therapies. OBJECTIVE: We assessed the safety and antitumor activity of intravesical pembrolizumab combined with BCG. DESIGN, SETTING, AND PARTICIPANTS: A 3 + 3 phase 1 trial of pembrolizumab + BCG was conducted in patients with BCG-unresponsive NMIBC (NCT02808143). INTERVENTION: Pembrolizumab was given intravesically (1-5 mg/kg for 2 h) beginning 2 weeks prior to BCG induction until recurrence. Urine profiling during treatment and spatial transcriptomic profiling of pre- and post-treatment tumors were conducted to identify biomarkers that correlated with response. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Safety and tolerability of immune checkpoint inhibition were assessed, and Kaplan-Meier survival analysis was performed. RESULTS AND LIMITATIONS: Nine patients completed therapy. Median follow-up was 35 months for five patients still alive at the end of the trial. The trial was closed due to the COVID-19 pandemic. Grade 1-2 urinary symptoms were common. The maximum tolerated dose was not reached; however, one dose-limiting toxicity was reported (grade 2 diarrhea) in the only patient who reached 52 weeks without recurrence. One death occurred from myasthenia gravis that was deemed potentially related to treatment. The 6-mo and 1-yr recurrence-free rates were 67% (95% confidence interval [CI]: 42-100%) and 22% (95% CI: 6.5-75%), respectively. Pembrolizumab was detected in the urine and not in blood. CD4+ T cells were significantly increased in the urine after treatment, and a transcriptomic analysis identified decreased expression of T-cell exhaustion markers in late recurrences. CONCLUSIONS: We demonstrate that intravesical pembrolizumab is safe, feasible, and capable of eliciting strong immune responses in a clinical setting and should be investigated further. PATIENT SUMMARY: Direct application of pembrolizumab to the bladder is a promising alternative for non-muscle-invasive bladder cancer unresponsive to Bacillus Calmette-Guérin and should be investigated further.


Subject(s)
COVID-19 , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/pathology , Administration, Intravesical , BCG Vaccine/adverse effects , Immune Checkpoint Inhibitors , Pandemics , Neoplasm Recurrence, Local/pathology , Neoplasm Invasiveness/pathology , Adjuvants, Immunologic
5.
Front Immunol ; 13: 978760, 2022.
Article in English | MEDLINE | ID: covidwho-2043449

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected half a billion people, including vulnerable populations such as cancer patients. While increasing evidence supports the persistence of SARS-CoV-2 months after a negative nasopharyngeal swab test, the effects on long-term immune memory and cancer treatment are unclear. In this report, we examined post-COVID-19 tissue-localized immune responses in a hepatocellular carcinoma (HCC) patient and a colorectal cancer (CRC) patient. Using spatial whole-transcriptomic analysis, we demonstrated spatial profiles consistent with a lymphocyte-associated SARS-CoV-2 response (based on two public COVID-19 gene sets) in the tumors and adjacent normal tissues, despite intra-tumor heterogeneity. The use of RNAscope and multiplex immunohistochemistry revealed that the spatial localization of B cells was significantly associated with lymphocyte-associated SARS-CoV-2 responses within the spatial transcriptomic (ST) niches showing the highest levels of virus. Furthermore, single-cell RNA sequencing data obtained from previous (CRC) or new (HCC) ex vivo stimulation experiments showed that patient-specific SARS-CoV-2 memory B cells were the main contributors to this positive association. Finally, we evaluated the spatial associations between SARS-CoV-2-induced immunological effects and immunotherapy-related anti-tumor immune responses. Immuno-predictive scores (IMPRES) revealed consistent positive spatial correlations between T cells/cytotoxic lymphocytes and the predicted immune checkpoint blockade (ICB) response, particularly in the HCC tissues. However, the positive spatial correlation between B cells and IMPRES score was restricted to the high-virus ST niche. In addition, tumor immune dysfunction and exclusion (TIDE) analysis revealed marked T cell dysfunction and inflammation, alongside low T cell exclusion and M2 tumor-associated macrophage infiltration. Our results provide in situ evidence of SARS-CoV-2-generated persistent immunological memory, which could not only provide tissue protection against reinfection but may also modulate the tumor microenvironment, favoring ICB responsiveness. As the number of cancer patients with COVID-19 comorbidity continues to rise, improved understanding of the long-term immune response induced by SARS-CoV-2 and its impact on cancer treatment is much needed.


Subject(s)
COVID-19 , Carcinoma, Hepatocellular , Liver Neoplasms , Comorbidity , Humans , Immune Checkpoint Inhibitors , Immunologic Memory , Morbidity , SARS-CoV-2 , Transcriptome , Tumor Microenvironment/genetics
6.
Thorac Cancer ; 13(20): 2911-2914, 2022 10.
Article in English | MEDLINE | ID: covidwho-2019069

ABSTRACT

Cytokine release syndrome (CRS) is a systemic inflammatory disease caused by a variety of factors, including infections and certain drugs. A 70-year-old man who was diagnosed with a postoperative recurrence of lung adenocarcinoma received nivolumab, ipilimumab, pemetrexed and carboplatin every 3 weeks for two cycles followed by nivolumab and ipilimumab, which resulted in a partial response. Four days after the dose of nivolumab, the patient returned with diarrhea and fever. The patient was diagnosed with COVID-19 infection accompanied by severe colitis. Although intensive care was performed, the patient suddenly went into cardiopulmonary arrest. Examination revealed an abnormally high interleukin-6 level, suggesting CRS. This is the first report of a patient with CRS accompanied with COVID-19 infection during treatment with ICIs. Cytokine release syndrome (CRS) is a systemic inflammatory disease caused by a variety of factors, including infections and certain drugs. Here, we report a case of non-small cell lung cancer with CRS caused by COVID-19 infection during treatment with nivolumab and ipilimumab. Fever is a common event in cancer patients, especially in COVID-19-infected patients, but when fever develops during cancer immunotherapy, CRS should always be kept in mind.


Subject(s)
COVID-19 , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Aged , COVID-19/complications , Carboplatin/therapeutic use , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Cytokine Release Syndrome , Humans , Immune Checkpoint Inhibitors , Interleukin-6/therapeutic use , Ipilimumab/therapeutic use , Lung Neoplasms/complications , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Male , Nivolumab/adverse effects , Pemetrexed/therapeutic use
7.
J Immunother ; 45(9): 389-395, 2022.
Article in English | MEDLINE | ID: covidwho-2018230

ABSTRACT

Immune checkpoint inhibitors (ICIs) can cause a variety of immune-related adverse events (irAEs). The coronavirus disease 2019 (COVID-19) is associated with increased amounts of pro-inflammatory cytokines, which may affect the outcome of irAEs. Data are limited regarding the impact of COVID-19 on irAEs in ICI-treated cancer patients. Hence, in this study, we retrospectively analyzed ICI-treated adult patients with malignant solid tumors at a single institution between August 2020 and August 2021. Patients who had the most recent ICI treatment over 1-month before or after the positive COVID-19 test were excluded from the study. For the COVID-19 positive group, only the irAEs that developed after COVID-19 infection were considered as events. A total of 579 patients were included in our study, with 46 (7.9%) in the COVID-19 positive group and 533 (92.1%) in the COVID-19 negative group. The baseline characteristics of patients in the 2 groups were similar. With a median follow-up of 331 days (range: 21-2226), we noticed a nonsignificant higher incidence of all-grade irAEs in the COVID-19 positive group (30.4% vs. 19.9%, P =0.18). The incidence of grade 3 and 4 irAEs was significantly higher in the COVID-19 positive group (10.9% vs. 3.2%, P =0.02). Multivariate analysis confirmed the association between COVID-19 infection and increased risk of severe irAE development (odds ratio: 1.08, 95% confidence interval: 1.02-1.14, P =0.01). Our study suggested that COVID-19 may pose a risk of severe irAEs in cancer patients receiving ICIs. Close monitoring and possibly delaying ICI administration could be considered when cancer patients are infected with COVID-19.


Subject(s)
Antineoplastic Agents, Immunological , COVID-19 , Neoplasms , Adult , Antineoplastic Agents, Immunological/therapeutic use , Cytokines , Humans , Immune Checkpoint Inhibitors/adverse effects , Neoplasms/complications , Neoplasms/drug therapy , Neoplasms/epidemiology , Retrospective Studies
8.
Int J Cancer ; 151(11): 1860-1873, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-1976728

ABSTRACT

Immune checkpoint inhibitor (ICI)-induced cardiotoxicity is a rare immune-related adverse event (irAE) characterized by a high mortality rate. From a pathological point of view, this condition can result from a series of causes, including binding of ICIs to target molecules on nonlymphocytic cells, cross-reaction of T lymphocytes against tumor antigens with off-target tissues, generation of autoantibodies and production of proinflammatory cytokines. The diagnosis of ICI-induced cardiotoxicity can be challenging, and cardiac magnetic resonance (CMR) represents the diagnostic tool of choice in clinically stable patients with suspected myocarditis. CMR is gaining a central role in diagnosis and monitoring of cardiovascular damage in cancer patients, and it is entering international cardiology and oncology guidelines. In this narrative review, we summarized the clinical aspects of ICI-associated myocarditis, highlighting its radiological aspects and proposing a novel algorithm for the use of CMR.


Subject(s)
Myocarditis , Antigens, Neoplasm , Autoantibodies , Cardiotoxicity/etiology , Cytokines , Humans , Immune Checkpoint Inhibitors/adverse effects , Magnetic Resonance Imaging , Myocarditis/chemically induced , Myocarditis/diagnostic imaging
9.
Nat Rev Clin Oncol ; 19(8): 494, 2022 08.
Article in English | MEDLINE | ID: covidwho-1972616
10.
Future Oncol ; 18(24): 2627-2638, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1957139

ABSTRACT

Patients with advanced, recurrent or metastatic cancer have poor prognosis despite treatment advancements. Vesicular stomatitis virus (VSV)-glycoprotein (GP; BI 1831169) is a chimeric VSV with its neurotropic glycoprotein G replaced by the non-neurotropic GP of the lymphocytic choriomeningitis virus. This live, recombinant oncolytic virus has demonstrated preclinical efficacy as a viral-based immunotherapy due to its interferon-dependent tumor specificity, potent oncolysis and stimulation of antitumor immune activity. Co-administration of the immune checkpoint inhibitor, ezabenlimab (BI 754091), alongside VSV-GP may synergistically enhance antitumor immune activity. Here, we describe the rationale and design of the first-in-human, phase I, dose-escalation study of VSV-GP alone and in combination with the immune checkpoint inhibitor ezabenlimab in patients with advanced, metastatic or relapsed and refractory solid tumors (NCT05155332).


There is a need to develop new treatments for people living with cancer. Immunotherapy is a type of medicine that works by helping the body's natural defenses, known as the immune system, to destroy cancer cells. There are different types of immunotherapies such as oncolytic viruses (OVs) and immune checkpoint inhibitors (ICIs). OVs are viruses that may help destroy cancer cells while leaving normal cells unharmed. They work by replicating within cancer cells; this causes them to burst and release more of the virus which then infects nearby cancer cells and activates the body's immune system. ICIs may be able to work together with OVs to amplify this effect. Vesicular stomatitis virus (VSV)-glycoprotein (GP) is a type of OV that has been shown to effectively destroy cancer cells in animal studies. This first-in-human study will investigate VSV-GP on its own and in combination with an ICI called ezabenlimab for the treatment of late-stage cancer or cancer that has spread to multiple parts of the body. Here, we describe the background and design of this study in progress which aims to find out if VSV-GP alone or in combination with ezabenlimab is effective against cancer, the suitable dose and if any side effects occur. Trial Registration Number: NCT05155332 (ClinicalTrials.gov).


Subject(s)
Neoplasms , Oncolytic Virotherapy , Oncolytic Viruses , Antibodies, Monoclonal , Cell Line, Tumor , Clinical Trials, Phase I as Topic , Glycoproteins , Humans , Immune Checkpoint Inhibitors , Neoplasms/genetics , Neoplasms/therapy , Oncolytic Viruses/genetics
11.
Immunotherapy ; 14(13): 1015-1020, 2022 09.
Article in English | MEDLINE | ID: covidwho-1952098

ABSTRACT

The exact impact of immune checkpoint inhibitors in the course and outcome of COVID-19 in cancer patients is currently unclear. Herein, we present the first description of an elderly melanoma patient who developed COVID-19 pneumonia while under treatment with nivolumab and bempegaldesleukin in combination with an investigational PEGylated interleukin (IL-2). We present the clinical characteristics and the laboratory and imaging findings of our patient during the course of COVID-19 pneumonia. Moreover, we discuss the currently available data regarding the mechanism of action of immune checkpoint inhibitors and IL-2 analogs in the treatment of COVID-19. The administration of these agents did not have a negative effect on the outcome of COVID-19 pneumonia in an elderly melanoma patient.


Immune checkpoint inhibitors represent a major advance in the treatment of several solid malignancies, including melanoma. Bempegaldesleukin is an investigational PEGylated IL-2 that is being evaluated, in combination with nivolumab, in the management of a variety of cancers. The immunomodulation caused by these agents may also modify the immune response in COVID-19. Currently available data regarding the impact of immune checkpoint inhibitors in reducing the severity of COVID-19 in patients with cancer are mixed, whereas no clinical data are available for bempegaldesleukin. Herein, we report the case of an elderly female melanoma patient who developed COVID-19 pneumonia while under treatment with nivolumab and bempegaldesleukin. The administration of these agents did not have a negative effect on the outcome of COVID-19 pneumonia in our patient.


Subject(s)
COVID-19 , Melanoma , Aged , COVID-19/drug therapy , Humans , Immune Checkpoint Inhibitors , Interleukin-2/therapeutic use , Melanoma/complications , Melanoma/drug therapy , Nivolumab/therapeutic use
12.
Lancet Oncol ; 23(8): 1078-1086, 2022 08.
Article in English | MEDLINE | ID: covidwho-1915191

ABSTRACT

BACKGROUND: Most kidney transplant recipients with cancer stop or reduce immunosuppressive therapy before starting treatment with an immune checkpoint inhibitor, and approximately 40% of such patients will develop allograft rejection. Isolated immunosuppression reduction might be associated with organ rejection. Whether immunosuppression manipulation, immune checkpoint inhibition, or both, induce organ rejection is difficult to ascertain. The aim of this study was to examine the risk of allograft rejection with immune checkpoint inhibitor exposure when baseline immunosuppression was left unchanged. METHODS: We conducted a multicentre, single-arm, phase 1 study in three hospitals in Australia. Kidney transplant recipients aged 18 years or older with incurable, locally advanced cancer or defined metastatic solid tumours were eligible if they had a creatinine concentration of less than 180 mmol/L, no or low concentrations of donor-specific HLA antibodies, and an Eastern Cooperative Oncology Group status of 0-2. Patients received standard doses of nivolumab (3 mg/kg intravenously every 14 days for five cycles, then 480 mg every 28 days for up to 2 years). The primary endpoint was the proportion of patients with irretrievable allograft rejection and no evidence of tumour response. Primary outcome analyses and safety analyses were done in the modified intention-to-treat population. This trial is registered with the Australian and New Zealand Clinical Trials Register, ANZCTR12617000741381, and is completed. FINDINGS: Between May 31, 2017, and Aug 6, 2021, 22 kidney transplant recipients with various solid tumours were screened and enrolled, four of whom chose not to proceed in the study and one of whom had unexpected disease progression. 17 patients (six [35%] women and 11 [65%] men; median age 67 years [IQR 59-71]) were allocated treatment with nivolumab and were included in the analyses. The trial was then stopped due to ongoing difficulties with running clinical trials during COVID-19 health restrictions. Patients were treated with a median of three infusions (IQR 2-10) and median follow-up was 28 months (IQR 16-34). No patients had irretrievable allograft rejection without evidence of tumour response. There were no treatment-related deaths or treatment-related serious adverse events. The most common grade 3 or grade 4 adverse events were decreased lymphocyte count in four (24%) patients, fever or infection in four (24%) patients, decreased haemoglobin in three (18%) patients, and increased creatinine in three (18%) patients. INTERPRETATION: Maintaining baseline immunosuppression before treatment with an immune checkpoint inhibitor in kidney transplant recipients might not affect expected efficacy and might reduce the risk of allograft rejection mediated by immune checkpoint inhibitors. FUNDING: Bristol Myers Squibb.


Subject(s)
COVID-19 , Kidney Transplantation , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Australia , Creatinine , Female , Humans , Immune Checkpoint Inhibitors/adverse effects , Kidney Transplantation/adverse effects , Male , Nivolumab
13.
J Thorac Oncol ; 17(8): 1002-1013, 2022 08.
Article in English | MEDLINE | ID: covidwho-1907383

ABSTRACT

INTRODUCTION: Patients with cancer have been prioritized for vaccination against severe acute respiratory syndrome coronavirus 2. Nevertheless, there are limited data regarding the safety, efficacy, and risk of developing immune-related adverse events (irAEs) associated with mRNA vaccines in patients with lung cancer, especially those being actively treated with immune checkpoint inhibitors. METHODS: This multicenter observational study was conducted at nine hospitals in Japan. Patients with lung cancer (≥20 y) actively treated with immune checkpoint inhibitors between 4 weeks prefirst vaccination and 4 weeks postsecond vaccination were enrolled. The primary end point was the incidence of irAEs of any grade on the basis of an assumed incidence without vaccination rate of 35%. Immunogenicity was assessed by measuring anti-spike (S)-IgG antibody levels against severe acute respiratory syndrome coronavirus 2. RESULTS: A total of 126 patients with lung cancer (median age, 71 y; interquartile range, 65-74) were enrolled from May to November 2021 and followed up until December 2021. There were 26 patients (20.6%, 95% confidence interval: 13.9%-28.8%) and seven patients (5.6%, 95% confidence interval: 2.3%-11.1%) who developed irAEs of any grade pre- and postvaccination, respectively, which was lower than the predicted incidence without vaccination. None of the patients experienced exacerbation of preexisting irAE postvaccination. S-IgG antibodies were seroconverted in 96.7% and 100% of the patients with lung cancer and controls, respectively, but antibody levels were significantly lower in patients with lung cancer (p < 0.001). CONCLUSIONS: Patients with lung cancer who were actively treated with ICIs were safely vaccinated without an increased incidence of irAEs; however, their vaccine immunogenicity was lower. This requires further evaluation.


Subject(s)
COVID-19 , Lung Neoplasms , Aged , COVID-19/prevention & control , Humans , Immune Checkpoint Inhibitors , Japan , Lung Neoplasms/drug therapy , SARS-CoV-2 , Vaccines, Synthetic , mRNA Vaccines
14.
Front Immunol ; 13: 900522, 2022.
Article in English | MEDLINE | ID: covidwho-1903024

ABSTRACT

Invasive fungal diseases (IFD) still cause substantial morbidity and mortality, and new therapeutic approaches are urgently needed. Recent data suggest a benefit of checkpoint inhibitors (ICI). We report the case of a diabetic patient with refractory IFD following a SARSCoV-2 infection treated by ICI and interferon-gamma associated with antifungal treatment.


Subject(s)
COVID-19 , Mucormycosis , Pulmonary Aspergillosis , Antifungal Agents/therapeutic use , COVID-19/complications , COVID-19/drug therapy , Humans , Immune Checkpoint Inhibitors/therapeutic use , Interferon-gamma/therapeutic use , Mucormycosis/complications , Mucormycosis/drug therapy
15.
Nat Cancer ; 3(9): 1039-1051, 2022 09.
Article in English | MEDLINE | ID: covidwho-1900671

ABSTRACT

Patients with cancer frequently receive immune-checkpoint inhibitors (ICIs), which may modulate immune responses to COVID-19 vaccines. Recently, cytokine release syndrome (CRS) was observed in a patient with cancer who received BTN162b2 vaccination under ICI treatment. Here, we analyzed adverse events and serum cytokines in patients with 23 different tumors undergoing (n = 64) or not undergoing (n = 26) COVID-19 vaccination under ICI therapy in a prospectively planned German single-center cohort study (n = 220). We did not observe clinically relevant CRS (≥grade 2) after vaccination (95% CI 0-5.6%; Common Terminology of Adverse Events v.5.0) in this small cohort. Within 4 weeks after vaccination, serious adverse events occurred in eight patients (12.5% 95% CI 5.6-23%): six patients were hospitalized due to events common under cancer therapy including immune related adverse events and two patients died due to conditions present before vaccination. Despite absence of CRS symptoms, a set of pairwise-correlated CRS-associated cytokines, including CXCL8 and interleukin-6 was >1.5-fold upregulated in 40% (95% CI 23.9-57.9%) of patients after vaccination. Hence, elevated cytokine levels are common and not sufficient to establish CRS diagnosis.


Subject(s)
COVID-19 Vaccines , COVID-19 , Neoplasms , COVID-19 Vaccines/adverse effects , Cohort Studies , Cytokine Release Syndrome , Cytokines , Humans , Immune Checkpoint Inhibitors , Immunotherapy/adverse effects , Interleukin-6 , Neoplasms/drug therapy , Vaccination
16.
Comput Math Methods Med ; 2022: 5430720, 2022.
Article in English | MEDLINE | ID: covidwho-1902135

ABSTRACT

Background: Over the last few years, the role of PDL1/PD-1 in pancreatic cancer development has received increasing attention, and this article is aimed at opening up new ideas for the medicine-based treatment of pancreatic cancer. Aims: To investigate the efficacy and safety of PDL1/PD-1 inhibitors versus FOLFIRINOX regimen in the treatment of advanced pancreatic cancer and its impact on patient survival and to provide a reference basis for clinical treatment of pancreatic cancer. Materials and Methods: The 116 pancreatic cancer patients treated in our hospital from September 2019 to September 2021 were selected and divided into 58 cases each in the (instance of watching, noticing, or making a statement) group and the comparison group according to the method based on random number table. The comparison group was treated with FOLFIRINOX, and the group was treated with PDL1/PD-1 stopper. The effectiveness, safety, and hit/effect on survival of the patients in the two groups were compared. Results: The median chemotherapy cycle for all patients was 4 (1-6), and the combined objective remission rate (0RR) was 36% and the disease control rate (DCR) was 80% after no chemotherapy in 116 patients, with 37.5% 0RR and 81.3% DCR in the observation group and 33.3% 0RR and 77.8% DCR in the comparison group. The greatest number of all patients reached SD, 44%; in the observation group, 43.8%; and in the comparison group, 44.5%. The rate of adverse reactions such as hematological toxicity, neutropenia, anemia, thrombocytopenia, nonhematological toxicity, vomiting, fatigue, infection, diarrhea, intestinal obstruction, and peripheral neuropathy was lower in 10.3% of patients in the observation group than in 25.8% of patients in the comparison group, which was significantly different by χ 2 test (P < 0.05). The median progression-free survival curve of the two groups was 19 months in the comparison group and 22 months in the observation group. The progression-free survival in the observation group was significantly higher than that in the comparison group, and there was a statistically significant difference between the two groups (P < 0.05). Conclusion: PDL1/PD-1 inhibitors in combination with FOLFIRINOX regimens have shown longer survival than treatment with FOLFIRINOX regimens for pancreatic cancer patients, with reliable clinical efficacy, tolerable adverse effects, and a high safety profile for patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Pancreatic Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fluorouracil , Humans , Immune Checkpoint Inhibitors , Irinotecan , Leucovorin , Oxaliplatin , Pancreatic Neoplasms/drug therapy , Programmed Cell Death 1 Receptor
17.
Am Soc Clin Oncol Educ Book ; 42: 1-13, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1879288

ABSTRACT

Patients with cancer generally have a higher risk of adverse outcomes from COVID-19, with higher age, male sex, poor performance status, cancer type, and uncontrolled malignant disease as the main risk factors. However, the influence of specific cancer therapies varies and raises concerns during the pandemic. In patients undergoing cancer immunotherapy or other immunosuppressive cancer treatments, we summarize the evidence on outcomes from COVID-19; address the safety, immunogenicity, and efficacy of COVID-19 vaccination; and review COVID-19 antiviral therapeutics for the patient with cancer. Despite higher mortality for patients with cancer, treatment with immune checkpoint inhibitors does not seem to increase mortality risk based on observational evidence. Inhibitory therapies directed toward B-cell lineages, including monoclonal antibodies against CD20 and CAR T-cell therapies, are associated with poor outcomes in COVID-19; however, the data are sparse. Regarding vaccination in patients receiving immune checkpoint inhibitors, clinical efficacy comparable to that in the general population can be expected. In patients undergoing B-cell-depleting therapy, immunogenicity and clinical efficacy are curtailed, but vaccination is not futile, which is thought to be due to the cellular response. Vaccine reactogenicity and toxicity in all groups of patients with cancer are comparable to that of the general population. Preexposure prophylaxis with monoclonal antibodies directed against the viral spike may provide passive immunity for those not likely to mount an adequate vaccine response. If infected, prompt treatment with monoclonal antibodies or oral small molecule antivirals is beneficial, though with oral antiviral therapies, care must be taken to avoid drug interactions in patients with cancer.


Subject(s)
COVID-19 , Neoplasms , Antibodies, Monoclonal/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immune Checkpoint Inhibitors , Immunologic Factors/therapeutic use , Immunotherapy , Neoplasms/drug therapy , SARS-CoV-2 , Vaccination
18.
Oncology ; 100(7): 392-398, 2022.
Article in English | MEDLINE | ID: covidwho-1861726

ABSTRACT

BACKGROUND: Immunogenicity of SARS-CoV-2 vaccines is modestly impaired in cancer patients due to a generally weakened immune system. Immune checkpoint inhibitors (ICI) are expected to enhance immune response. This has already been described to be the case in influenza vaccines, and first data about COVID-19 vaccines show a trend in this direction. AIM: We aimed to investigate the immune response of patients with melanoma under ICI therapy after COVID-19 vaccination. PATIENTS AND METHODS: In the Skin Cancer Center Hanover (Germany), we recruited 60 patients with advanced melanoma who either received ICI therapy during or before the vaccination period. Serological blood analysis was performed using quantitative ELISA for Anti-SARS-CoV-2 spike protein 1 IgG antibodies. RESULTS: We did not observe an enhanced humoral immune response in patients under active or past ICI therapy after COVID-19 vaccination. Nevertheless, there is a tendency of higher antibody levels when ICI therapy was received within the last 6 months before vaccination. Subgroup analysis revealed that patients in our study population under ongoing targeted therapy during vaccination period had significantly higher median antibody levels than patients without any active antitumor treatment. CONCLUSION: Melanoma patients under ICI therapy show comparable antibody response after SARS-CoV-2 vaccination to healthy health care professionals. This finding is independent of the timing of ICI therapy.


Subject(s)
COVID-19 , Melanoma , Antibodies, Viral/metabolism , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immune Checkpoint Inhibitors/therapeutic use , Melanoma/drug therapy , SARS-CoV-2 , Vaccination
19.
BMC Cancer ; 22(1): 551, 2022 May 16.
Article in English | MEDLINE | ID: covidwho-1849686

ABSTRACT

BACKGROUND: Immune-mediated pneumonitis has a high mortality rate; however, information regarding the related risk factors remains limited. This study aimed to analyze risk factors for pneumonitis, including smoking and lung metastasis (LM), in patients with extrapulmonary primary tumors. METHODS: Data of 110 patients treated with immune checkpoint inhibitors (ICIs) (nivolumab/pembrolizumab) for treating extrapulmonary primary tumors at the Shiga University of Medical Science Hospital between January 2015 and December 2019 were retrospectively collected. The association between the onset of pneumonitis and treatment-related factors was analyzed by logistic regression. The severity of pneumonitis was graded according to the Common Terminology Criteria for Adverse Events version 5.0. Risk factors, such as the absence or presence of interstitial lung disease (ILD) and LM, or other clinical factors, including smoking status before ICI administration, were analyzed. RESULTS: Multivariate analyses indicated that the amount of smoking was significantly associated with an increase in the development of all-grade pneumonitis types (odds ratio (OR) = 20.33, 95% confidence interval (CI) = 20.03-20.66; p = 0.029). LM and ILD were significantly related to an increase in the development of symptomatic pneumonitis (≥ Grade 2) (OR = 10.08, 95% CI = 1.69-199.81; p = 0.076, and OR = 6.76, 95% CI = 1.13-40.63; p = 0.037, respectively). CONCLUSIONS: Pre-screening for ILD and LM and recognizing patients' smoking history is important for determining the risk of ICI-induced pneumonitis and allowing safe ICI administration.


Subject(s)
Lung Diseases, Interstitial , Lung Neoplasms , Pneumonia , Humans , Immune Checkpoint Inhibitors/adverse effects , Lung Diseases, Interstitial/complications , Lung Neoplasms/complications , Lung Neoplasms/drug therapy , Pneumonia/diagnosis , Retrospective Studies , Risk Factors
20.
Emerg Infect Dis ; 28(7): 1518-1520, 2022 07.
Article in English | MEDLINE | ID: covidwho-1809305

ABSTRACT

Recently, along with increasing use of immune checkpoint inhibitors such as nivolumab, the incidence of immune-related adverse events, including type 1 diabetes mellitus, has become a serious problem. We report a patient who had immune checkpoint inhibitor‒associated type 1 diabetes mellitus that developed after a second mRNA-based SARS-CoV-2 vaccination.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Diabetes Mellitus, Type 1/chemically induced , Immune Checkpoint Inhibitors/adverse effects , Nivolumab/adverse effects , SARS-CoV-2/immunology , Humans , Japan , Vaccination/adverse effects
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