Immunotherapy: SYNERGISTIC PERITONEAL ANTI-TUMOR EFFECT OF ALLOCETRAOTS, A CELLULAR IMMUNE-THERAPY, IN COMBINATION WITH IMMUNE CHECKPOINT INHIBITORS/CHEMOTHERAPY, THROUGH IN-VIVO REPROGRAMMING OF MACROPHAGES AND DENDRITIC CELLS

Background & Aim: Immune checkpoint inhibitors (ICI) revolutionized solid tumor treatment, however, in many tumors only partial response is achieved. Allocetra-OTS has an immune modulating effect on macrophages and dendritic cells and showed an excellent safety profile in patients including patients with sepsis and Covid-19. Here we investigated the anti-tumoral effect of Allocetra-OTS cellular therapy, in peritoneal solid tumor animal models. Methods, Results & Conclusion(s): Allocetra-OTS is manufactured from enriched mononuclear fractions and induced to undergo early apoptosis. Balb/c mice were inoculated intraperitoneally (IP) with AB12 (mesothelioma) with pLenti-PGK-V5-Luc-Neo and treated with anti- CTLA4 with or without Allocetra-OTS. Mice were monitored daily for clinical score and weekly using IVIS (Fig.1). Kaplan-Meier log rank test was done for survival. For Allocetra-OTS preparation, enriched mononuclear fractions were collected by leukapheresis from healthy eligible human donors and induced to undergo early apoptosis. Anti- CTLA4 standalone therapy significantly improved survival (Fig.2) from mean 34+/-9 to 44.9 +/-20 days. However, OTS standalone therapy was non-inferior and improved survival to 52.3 +/-20 days. Anti-CTLA4 + Allocetra-OTS combination therapy, ameliorated survival to 86.7+/-20 days with complete cancer remission in 60-100% of mice. Similar anti- tumoral effects of Allocetra-OTS were seen in mesothelioma model in a combination therapy with either anti-PD1 or cisplatin and using anti-PD1 in ID8 ovary cancer model. Based on single cell analysis confirmed by flow cytometry and pathology, the mechanism of action seems to be related or at least associated with an increase in f/480high peritoneal macrophages and a decrease in recruited macrophages, and to f/480high infiltration of the tumor. However, further studies are needed to confirm these observations. During IP tumor progression, Allocetra-OTS as a standalone therapy or in combination with ICI, or cisplatin, significantly reduced tumor size and resulted in complete remission in up to 100% treated mice. Similar results were obtained in ID8 ovary cancer. Based on excellent safety profile in > 50 patients treated in prior clinical trials for sepsis and Covid-19, Phase I/II clinical trial of Allocetra-OTS plus chemotherapy has started and three patient already recruited. A second phase I/II clinical trial of Allocetra- OTS plus anti-PD1, as a second- and third-line therapy in various cancers, was initiated in Q1 2023. [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy

Outcomes of cancer patients with Covid-19 admitted to the Intensive Care Unit: A retrospective study

Introduction: Active cancer increases the odds of death among patients with COVID-19.1 Cancer patients may be at increased risk of complications and mortality from COVID-19 owing to the systemic effects of malignancy, immune suppression after chemotherapy, treatment-related complications and presence of co-morbidities.2 They may develop serious complications necessitating ICU admission. In a meta-analysis, the pooled mortality in cancer patients with COVID-19 admitted to an ICU was 60.2%.3 Our hospital is a tertiary referral cancer centre, and the ICU admitted cancer patients with Covid-19 throughout the pandemic. Objective(s): To determine the 30-day in-hospital mortality of adult cancer patients with Covid-19 admitted to the ICU. We also aimed to determine the factors associated with mortality in cancer patients with Covid-19. Method(s): After approval from the Institutional Ethics Committee, data of all cancer patients (age = 16 years) with Covid-19 admitted to the ICU between March 2020 and March 2021 were retrieved from the hospital records. In case of multiple ICU admissions, data from the first admission was recorded. Data recorded included demographic details, type of cancer (solid, haematological), surgical status, APACHE-II and SOFA scores, C-reactive protein, and interventions in ICU. The primary outcome was 30-day in-hospital mortality. Data were analysed using Man-Whitney test and chi-square test. A multivariable regression analysis was carried out to determine factors associated with mortality. Result(s): Data of 127 cancer patients with Covid-19 was analysed. The median [interquartile range, IQR] age was 55 (43-62) years, and there were 50 females (39.3%). Comorbidities were present in 46 (36%) patients, the commonest being diabetes (29 patients) and hypertension (31 patients). The median [IQR] APACHE-II and SOFA scores were 15[8-20] and 4[2-7], respectively. Overall, 62/127 patients died, and 30-day hospital mortality was 49%. There were 30 patients with haematological malignancy and 97 with solid tumours with 30-day in-hospital mortality rates of 46.7% and 49.5%, respectively;p = 0.84). Amongst patients with solid tumours, there was no difference in mortality in surgical patients compared to non-surgical patients (43.3% vs. 52.2%;p = 0.42). Table 1 summarises the parameters and interventions in survivors and non-survivors. On multivariable analysis, only the change in SOFA score from Day 1 to Day 3 was independently associated with outcome (Odds ratio 1.36 (95% confidence interval 1.01-1.84, p-0.04). Conclusion(s): In patients with cancer and Covid-19 and age =16 years admitted to our ICU, the crude 30-day hospital mortality was 47%. There was no association of mortality with cancer type or surgical status. The only independent predictor of mortality was progression of organ failure. Cancer patients with Covid-19 have a reasonable outcome and should be given a trial of intensive care.

A retrospective analysis of first-line PD-1 monoclonal antibodies treatment in patients with leptomeningeal metastasis from solid tumors.

INTRODUCTION: Patients whose solid tumors (ST) show leptomeningeal metastasis (LM) have very poor prognosis and short overall survival. The aim of this study was to evaluate the efficacy of first-line programed death-1(PD-1) monoclonal antibody (mAb) treatment in these patients. METHODS: We retrospectively evaluated patients diagnosed with LM from ST who were treated with first-line PD-1 mAb at our hospital between April 1 and November 30, 2019. We analyzed their clinicopathological characteristics and response to the treatment. RESULTS: We collected and analyzed data from 6 patients with different primary ST. 5 patients received PD-1 mAb combined with chemotherapy and/or anti-angiogenic drugs, while one received only PD-1 mAb. The median (range) number of treatment cycles was 5.5 (1-21). PD-1 mAb treatment did not cause neurotoxicity. The time period of first assessment varied from 21 to 65 days after treatment. Among 5 patients who got obvious symptoms relief, 4 patients persisted for > 3 months and even showed a reduction in the number of tumor cells in cerebrosprinal fluid. Ventriculoperitoneal (VP) shunt was used to treat hydrocephalus observed beneficial in 3 patients: 2 before and 1 after PD-1 mAb treatment. The median (range) follow-up time was 214 (57-460) days. 4 patients died. The overall survival ranged from 57 days to at least 460 days. 1 of the two alive patients continued to show no worsening of symptoms after 457 days. CONCLUSIONS: Patients with LM from ST can benefit from first-line PD-1 mAb combined treatment without additional neurotoxicity. Further research is required to validate the safety and efficacy.

SARS-CoV-2 VACCINE-INDUCED T CELL RESPONSES IN CANCER PATIENTS UNDERGOING TREATMENT

Background: mRNA vaccines have proven useful in protecting vulnerable populations against SARS-CoV-2 infection. However, certain therapeutics, specifically those used in cancer treatment, reduce mRNA vaccine-induced humoral responses against SARS-CoV-2. The effects on T cell responses are not well characterized. Here, we evaluate SARS-CoV-2 spike-specific T cell responses over the course of one year in solid tumor patients in BC, Canada. Method(s): 18 female, solid-tumor patients from the BC Cancer Agency were enrolled in this prospective, cohort study, with 7 patients receiving cytotoxic chemotherapy and 11 patients receiving non-cytotoxic treatments. Whole blood was collected 1-month (T1) and one-year +/- 1-month (T2) post series completion (2 mRNA doses). Antigen-induced marker assays (AIM assays) were used to quantify CD4+ and CD8+ T cell responses, where whole blood was stimulated with ancestral or omicron SARS-CoV2 Spike peptide pools or unstimulated for 48 hours at 37degree C, fluorescently stained for activation markers CD25 and OX40 (CD4+ T cells) or CD69 and CD137 (CD8+ T cells), and analyzed using a 5-laser flow cytometer. Phenotyping of antigen-specific CD4+ T cells was done in parallel to assess the frequency of spike-specific Tregs, Th1, Th2, Th9, Th17, and Th17.1 cells. Result(s): All individuals had detectable levels of spike-specific CD4+ T cells at T2, while only 72.2% of individuals had detectable levels of spike-specific CD8+ T cells. Treatment type did not significantly impact the magnitude or phenotype of T cell responses, including those to Omicron. However, increased age was associated with decreased ancestral CD8+ T cell responses at T2. Further, ancestral and omicron responses were significantly different at T2, with decreased magnitude and altered phenotype of omicron-specific CD4+ T cells. Conclusion(s): Here, we report that solid tumor patients, treated with either chemotherapy or biologics, mount robust T cell immunity to SARS-CoV-2 following vaccination. Additional data is needed to determine if these responses correlate with antibody levels and clinical illness.

Comorbidities Associated With Myocarditis In Hospitalized COVID-19 Patients

Introduction: While COVID-19 is predominantly a lung infection, it can cause systemic viremia in susceptible patients and lead to cardiac involvement and myocarditis (MC);an inflammation of the myocardium characterized by arrhythmias, cardiogenic shock, acute heart failure, and death. Although rare, there is evidence of a surge in MC-related admissions during the COVID-19 pandemic, implying a correlation. However, the risk factors associated with MC susceptibility in these patients remain unclear. This study aims to assess the comorbidities and demographic features associated with the development of MC in adult patients with COVID-19. Method(s): Data were obtained from the PearlDiver database (PearlDiver Technologies, Fort Wayne, IN). The database provides all-payers administrative claims data on the patient level. Using ICD-10-CM codes, a cohort of patients hospitalized with a primary diagnosis of COVID-19 was identified. The study included only patients admitted to the hospital between January and October 2020 to minimize bias associated with vaccine-related MC. Within this cohort, patients diagnosed with MC during and up to one month after admission were identified and their demographic features and comorbidities to were compared to those without MC. We calculated Risk Ratios with their respective 95% CI. A p-value <0.05 was deemed significant. Result(s): We found 627,465 admissions due to COVID-19 from January to October 2020, with 506 (0.08 %) diagnosis of MC. Patients with MC were more likely to be males (60%), younger (mean age 48, SD= 23 vs. 60, SD =17 - p<0.01), and they had more comorbidities (mean Elixhauser Comorbidity Index: 7.52, SD= 5 vs. 6.9, SD = 5 - p<0.001). The development of MC was significantly associated with a history of coagulopathies [0.55(0.46-0.66);p<0.0001], asthma [1.20 (1.06-1.23);p= 0.01], deep venous thrombosis [1.54(1.38-1.68);p<0.0001], renal disease[1.15 (1.02-1.27);p= 0.03], congestive heart failure [1.24 (1.12-1.34);p=0.006], ischemic heart disease [1.25 (1.14-1.35);p=0.0001], and arrhythmias [1.24 (1.14-1.32);p< 0.0001]. However, a history of diabetes [0.89 (0.67-0.99);p=0.02], hypertension [0.71 (0.62-0.80);<0.000.1], depression [0.71(0.52-0.88);p=0.0001], and hypothyroidism [0.42(0.08-0.69);p<0.0001] was associated with lower risk of MC-related hospitalization. Other preexistent conditions including, psychosis, rheumatoid arthritis, cerebrovascular disease, obesity, tobacco use, alcohol abuse, HIV, anemia, peripheral vascular disease, and non-metastatic solid tumor were not significantly correlated with MC. Discussion(s): MC is a rare yet serious complication of COVID-19. Therefore, a better knowledge of the pathophysiology of COVID-19 and the patient factors associated with development to MC is crucial for prognostication and providing risk-adjusted treatment. Conclusion(s): Patients with a history of cardiovascular disease, renal and pulmonary disease were more likely to develop MC as a result of COVID-19. However, hypertension and diabetes were associated with lower risk of MC, which warrants further investigation.Copyright © 2022

Adult Patients with Cancer Have Impaired Humoral Responses to Complete and Booster COVID-19 Vaccination, Especially Those with Hematologic Cancer on Active Treatment: A Systematic Review and Meta-Analysis.

The exclusion of patients with cancer in clinical trials evaluating COVID-19 vaccine efficacy and safety, in combination with the high rate of severe infections, highlights the need for optimizing vaccination strategies. The aim of this study was to perform a systematic review and meta-analysis of the published available data from prospective and retrospective cohort studies that included patients with either solid or hematological malignancies according to the PRISMA Guidelines. A literature search was performed in the following databases: Medline (Pubmed), Scopus, Clinicaltrials.gov, EMBASE, CENTRAL and Google Scholar. Overall, 70 studies were included for the first and second vaccine dose and 60 studies for the third dose. The Effect Size (ES) of the seroconversion rate after the first dose was 0.41 (95%CI: 0.33-0.50) for hematological malignancies and 0.56 (95%CI: 0.47-0.64) for solid tumors. The seroconversion rates after the second dose were 0.62 (95%CI: 0.57-0.67) for hematological malignancies and 0.88 (95%CI: 0.82-0.93) for solid tumors. After the third dose, the ES for seroconversion was estimated at 0.63 (95%CI: 0.54-0.72) for hematological cancer and 0.88 (95%CI: 0.75-0.97) for solid tumors. A subgroup analysis was performed to evaluate potential factors affecting immune response. Production of anti-SARS-CoV-2 antibodies was found to be more affected in patients with hematological malignancies, which was attributed to the type of malignancy and treatment with monoclonal antibodies according to the subgroup analyses. Overall, this study highlights that patients with cancer present suboptimal humoral responses after COVID-19 vaccination. Several factors including timing of vaccination in relevance with active therapy, type of therapy, and type of cancer should be considered throughout the immunization process.

Lorigerlimab, a bispecific PD-13CTLA-4 DART molecule in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): A phase 1 expansion (exp) cohort

Background: Lorigerlimab (MGD019) is an investigational, bispecific Fc-bearing (IgG4) DART molecule designed to enhance CTLA-4 blockade on dual expressing, tumor infiltrating lymphocytes, while maintaining maximal PD-1 blockade on PD-1 expressing cells. Lorigerlimab has approximate dose proportional PK across 1-10 mg/kg IV dosing Q3W, with sustained PD-1 receptor occupancy evident at doses >=1 mg/kg Q3W. MGD019-01 is a global first-in-human dose finding and activity estimating study of lorigerlimab in advanced solid tumors (AST). Method(s): The exp phase of MGD019-01 evaluates single agent safety, PK, and antitumor effects of lorigerlimab at the recommended dose for exp of 6 mg/ kg IV Q3W in 4 tumor specific cohorts. Confirmed responses were noted in each cohort. Preliminary results of the mCRPC cohort are reported here. Response evaluable pts received >=1 dose and had >=1 postbaseline imaging evaluation. Measurable lesions were evaluated per RECIST v1.1 and skeletal metastases assessed by bone scan. Prostate specific antigen (PSA) response was defined as a >=50% (PSA50) or>=90% (PSA90) PSA decline from baseline with confirmation>=3 weeks later. Expression of proliferation marker, Ki67, and inducible costimulator (ICOS) by peripheral T cells was assessed by flow cytometry. Result(s): At data cutoff (9/10/22), 127 pts with AST received >=1 dose of lorigerlimab 6 mg/ kg. Median exposure was 10 weeks (range, 0.1, 94.4) with median of 4 infusions. 6 pts remain on therapy;36 discontinued for PD (n=13), AEs (n=17), or patient/physician decision (n=6). Treatment related adverse events (TRAE) occurred in 109/127 (85.8%) pts. TRAEs occurring in>=15% of pts were fatigue, pruritus, hypothyroidism, pyrexia. Rates of grade >=3 TRAEs and immune-related AEs were 32.3% and 7.9%, respectively. AEs leading to drug discontinuation occurred in 22.8% of pts. There were no fatal AEs related to lorigerlimab. In the mCRPC exp cohort (n=42), pts had a median of 2 prior lines of therapy for CRPC, >80% received prior ART or taxanes;88% had visceral (liver, 26%;lung, 26%) or nodal disease and 95% had bone metastases. 42 pts were PSA response evaluable;35 were RECIST evaluable. ORR was 25.7% (9/35;9 confirmed PRs). Median duration of response was 16.1 weeks (range 6-25+ weeks). 5 responders remain on study, 4 discontinued for unrelated fatal AEs: COVID-19 (2) cardiac arrest (1) C. difficile infection (1). Confirmed PSA50 and PSA90 response rates were 28.6%(12/42) and 21.4% (9/42), respectively. Increased frequencies of Ki67+ and ICOS+ T cells were observed on day 8 posttreatment compared to pretherapy per the flow cytometry analyses from 35 pts. Conclusion(s): Lorigerlimab demonstrates a manageable safety profile with evidence of encouraging and durable antitumor activity in a chemotherapy refractory mCRPC population. Randomized evaluation of lorigerlimab in mCRPC is warranted.

COVID-19 Adverse Outcomes in Immunocompromised Patients

Background: Coronavirus disease 2019 (COVID-19) is a devastating viral pandemic infecting millions of people with a wide range of symptoms from fever to death. It has been suggested that immunocompromised patients are at a higher risk of severe disease, poor clinical outcomes, and mortality. However, these patients' risk factors and COVID-19-related outcomes are not well characterized. Objective(s): We evaluated the COVID-19-related outcomes among immunocompromised patients ranging from solid tumors, hema-tological malignancies, and HIV to autoimmune disease and transplant recipients who received immunosuppressive agents. We also aimed at finding risk factors related to mortality among immunocompromised patients with COVID-19. Method(s): This cross-sectional study was conducted in Khansari Hospital, Iran between March and November 2021. We included immunocompromised patients with nasal swab positive SARS-CoV-2 polymerase chain reaction (PCR) results in the study. Patient outcomes, including hospitalization ward and the mortality rate, were assessed till three months after COVID-19 infection were evaluated in all patients. Moreover, the relation between risk factors and the rate of the mortality rate was analyzed in immuno-compromised patients with COVID-19. Result(s): A total number of 74 immunocompromised patients with solid tumors, hematologic malignancies, autoimmune diseases, acquired immunodeficiencies, and solid-organ transplant recipients were included in the study. Results indicated that the male gender and ICU hospitalization significantly increase the mortality risk. Surprisingly, chemotherapy is associated with a lower risk of mortality. Conclusion(s): Identifying the risk factors can improve the decision-making on cancer patients' management during the COVID-19 infection. A further large cohort of patients would be required to identify risk factors relating to poor clinical outcomes and mortality rates in immunocompromised patients with COVID-19.Copyright © 2023, Author(s).

Original Article Evaluation of clinical outcomes, laboratory and imaging data of patients with solid tumor infected with COVID-19 infection

Background: COVID-19 is associated with higher mortality rates in patients with cancer. In this study, we aimed to evaluate the clinical outcomes, and laboratory and imaging data of patients with solid tumor infected with COVID-19 infection. Method(s): This is a cross-sectional retrospective study performed in 2020-2022 on 85 patients with a previous diagnosis of solid tumors infected with COVID-19. We included all patients with tumors of solid organs that were diagnosed with COVID-19 infection and required hospitalization those patients previously hospitalized for treatments and were infected with COVID-19 during hospitalization. Demographic data of patients were collected using a checklist. We collected data regarding clinical outcome (discharge, hospitalization or death), duration of hospitalization, requiring ICU admission, duration of hospitalization divided by received drugs and type of tumor and mean survival time. Furthermore, we collected laboratory data from all patients. The radiologic characteristics of patients were also extracted from their data. Result(s): Breast cancer was the most common solid tumor (34.9%), followed by lung cancer (19.3%). The mortality rate was 24.1% (20 patients). The highest mortality rate in this study was for metastatic intestinal cancer to the lung (100%, one patient), followed by metastatic prostatic cancer to lung (50%, three patients). The highest hospitalization duration was for patients with glioblastoma multiform (GBM) (30 days). The mean survival time among patients with mortality was 19.15+/-1.80 days. The mean CT severity score of all patients was 27.53+/-22.90. Patient's most common radiologic sign was air space consolidation (89.1%). The highest CT severity score was found in patients with stomach cancer (46.67+/-5.77). Conclusion(s): The mortality rate in this study was 24.1%. Based on the results of our study and previous research, special care should be provided to patients with solid tumors during the COVID-19 pandemic and in infected cases.Copyright © 2022, E-Century Publishing Corporation. All rights reserved.

Neutralising antibody titers and COVID outcomes in cancer patients

Background: Cancer patients are at high risk of severe COVID infection and recommended at least three doses of SARS-CoV2 mRNA vaccines. Various anti-neoplastic treatments may affect long-term vaccine immunogenicity. Methods: Patients with solid or haematological cancer were recruited from two Singapore hospitals between July 2021 and March 2022. GenScript cPASS surrogate virus neutralisation assays measured antibody responses, which were correlated with clinical outcomes obtained from medical records and national mandatory-reporting databases. Results: In total, 273 patients were recruited (40 with haematological malignancies and the rest solid tumours). Two-hundred and four patients (74.7%) were receiving active cancer therapy: 98 (35.9%) receiving systemic chemotherapy and the rest targeted or immunotherapy. All patients were seronegative at baseline. After receiving one, two and three doses of SARS-CoV-2-mRNA vaccination, seroconversion rate was 35.2%, 79.4% and 92.4% respectively. After three doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) as compared to patients on immunotherapy (94.1%±9.56, p<0.05) and chemotherapy (92.8%±18.1, p<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients of which 18 were severe. Conclusion: This study demonstrates high immunogenicity of three doses of vaccines and protection against severe infection in cancer patients.

Evaluation of clinical outcomes, laboratory and imaging data of patients with solid tumor infected with COVID-19 infection.

BACKGROUND: COVID-19 is associated with higher mortality rates in patients with cancer. In this study, we aimed to evaluate the clinical outcomes, and laboratory and imaging data of patients with solid tumor infected with COVID-19 infection. METHODS: This is a cross-sectional retrospective study performed in 2020-2022 on 85 patients with a previous diagnosis of solid tumors infected with COVID-19. We included all patients with tumors of solid organs that were diagnosed with COVID-19 infection and required hospitalization those patients previously hospitalized for treatments and were infected with COVID-19 during hospitalization. Demographic data of patients were collected using a checklist. We collected data regarding clinical outcome (discharge, hospitalization or death), duration of hospitalization, requiring ICU admission, duration of hospitalization divided by received drugs and type of tumor and mean survival time. Furthermore, we collected laboratory data from all patients. The radiologic characteristics of patients were also extracted from their data. RESULTS: Breast cancer was the most common solid tumor (34.9%), followed by lung cancer (19.3%). The mortality rate was 24.1% (20 patients). The highest mortality rate in this study was for metastatic intestinal cancer to the lung (100%, one patient), followed by metastatic prostatic cancer to lung (50%, three patients). The highest hospitalization duration was for patients with glioblastoma multiform (GBM) (30 days). The mean survival time among patients with mortality was 19.15±1.80 days. The mean CT severity score of all patients was 27.53±22.90. Patient's most common radiologic sign was air space consolidation (89.1%). The highest CT severity score was found in patients with stomach cancer (46.67±5.77). CONCLUSION: The mortality rate in this study was 24.1%. Based on the results of our study and previous research, special care should be provided to patients with solid tumors during the COVID-19 pandemic and in infected cases.

COVID-19 Vaccines and Immunosuppressed Patients With Cancer: Critical Considerations.

BACKGROUND:  Patients with cancer are highly vulnerable to COVID-19 because of immunosuppression from diseases and treatments. Emerging data characterize the impact of COVID-19 vaccines related to cancer malignancies and treatments. OBJECTIVES:  This article provides a clinical foundation on the immune response to the COVID-19 vaccine associated with the impact of cancer and its related treatments. It reviews strategies for vaccine scheduling, Centers for Disease Control and Prevention recommendations, and nursing considerations when administering the vaccine to immunosuppressed patients. METHODS:  Research studies about immune responses to COVID-19 vaccines among immunosuppressed patients with hematologic and solid tumor malignancies were summarized. FINDINGS:  Studies about the humoral immune responses of patients with cancer to COVID-19 vaccines help guide vaccination planning for this population. Critical nursing considerations for patients with cancer receiving COVID-19 vaccination are integral to the provision of optimal clinical oncology care during the pandemic.

COVID-19 vaccination in patients with cancer: Opportunities and challenges.

The rapid spread of the SARS-Cov-2 virus, the increase in the number of patients with severe COVID-19, and the high mortality rate created the basis for the production of safe and effective vaccines. Studies have confirmed the increased risk of severe Covid-19 disease and mortality in cancer patients. It is logical that cancer patients should be the first to receive the primary vaccination and the booster vaccine for Covid-19. Since studies related to cancer patients and the effectiveness of existing Covid-19 vaccines have not been widely conducted, there are significant uncertainties about the effectiveness of the vaccine and the level of humoral and cellular immune responses in these patients. As a result, the possible risks and side effects of existing vaccines are not clear for patients with different cancers who are undergoing special treatments. In this study, we will discuss the effectiveness and safety of existing vaccines on cancer patients. In addition, we highlight factors that could affect the effectiveness of vaccines in these patients and finally discuss opportunities and challenges related to vaccination in cancer patients.

The impact of anti-tumor approaches on the outcomes of cancer patients with COVID-19: a meta-analysis based on 52 cohorts incorporating 9231 participants.

BACKGROUND: This study was designed to investigate the impact of anti-tumor approaches (including chemotherapy, targeted therapy, endocrine therapy, immunotherapy, surgery and radiotherapy) on the outcomes of cancer patients with COVID-19. METHODS: Electronic databases were searched to identify relevant trials. The primary endpoints were severe disease and death of cancer patients treated with anti-tumor therapy before COVID-19 diagnosis. In addition, stratified analyses were implemented towards various types of anti-tumor therapy and other prognostic factors. Furthermore, odds ratios (ORs) were hereby adopted to measure the outcomes with the corresponding 95% confidence intervals (CIs). RESULTS: As indicated in the study consisting of 9231 individuals from 52 cohorts in total, anti-tumor therapy before COVID-19 diagnosis could elevate the risk of death in cancer patients (OR: 1.21, 95%CI: 1.07-1.36, P = 0.0026) and the incidence of severe COVID-19 (OR: 1.19, 95%CI: 1.01-1.40, P = 0.0412). Among various anti-tumor approaches, chemotherapy distinguished to increase the incidence of death (OR = 1.22, 95%CI: 1.08-1.38, P = 0.0013) and severe COVID-19 (OR = 1.10, 95%CI: 1.02-1.18, P = 0.0165) as to cancer patients with COVID-19. Moreover, for cancer patients with COVID-19, surgery and targeted therapy could add to the risk of death (OR = 1.27, 95%CI: 1.00-1.61, P = 0.0472), and the incidence of severe COVID-19 (OR = 1.14, 95%CI: 1.01-1.30, P = 0.0357) respectively. In the subgroup analysis, the incidence of death (OR = 1.17, 95%CI: 1.03-1.34, P = 0.0158) raised in case of chemotherapy adopted for solid tumor with COVID-19. Besides, age, gender, hypertension, COPD, smoking and lung cancer all served as potential prognostic factors for both death and severe disease of cancer patients with COVID-19. CONCLUSIONS: Anti-tumor therapy, especially chemotherapy, augmented the risk of severe disease and death for cancer patients with COVID-19, so did surgery for the risk of death and targeted therapy for the incidence of severe COVID-19.

Short term safety of coronavirus disease 2019 vaccines in patients with solid tumors receiving systemic therapy.

BACKGROUND: There are currently three coronavirus disease 2019 (COVID-19) vaccines approved by the United States Food and Drug Administration to prevent coronavirus infection. However, robust data are unavailable on the adverse events of the vaccines in patients with solid tumor malignancies undergoing systemic therapies. AIM: To evaluate the safety of COVID-19 vaccines in patients with solid tumors undergoing systemic therapies. METHODS: The study included patients with solid tumors treated in an academic tertiary care center who received COVID-19 vaccination between January 1, 2021 and August 15, 2021, while undergoing systemic therapy. Electronic medical records were accessed to collect information on patient characteristics, systemic therapies, type of vaccine received, and adverse effects associated with the vaccine administration. Adverse events (AEs) were graded according to Common Terminology Criteria for Adverse Events, version 5.0. RESULTS: The analysis included 210 patients; the median age was 70 years, and 51% of patients were female. The most common chemotherapy, immunotherapy, and targeted therapy administered were taxane-based regimens 14.2% (30/210), anti-programmed death 1 (PD-1) agents 22.8% (48/210), and antiangiogenic agents 7.1% (15/210), respectively. The most common cancers were gastrointestinal 43.8% (92/210), thoracic 30.4% (64/210), and genitourinary 17.6% (37/210). Patients received the following vaccines: 2 doses of BNT162b2 by Pfizer 52% (110/210), 2 doses of mRNA-1273 by Moderna 42% (89/210), and 1 dose of JNJ-78436735 by Johnson & Johnson 5% (11/210). At least 1 AE attributable to the vaccine was observed in 37 patients 17.6% (37/210). The total number of AEs attributable to vaccines was 62: Fifty-three grade 1 and nine grade 2. Most adverse events occurred after the second dose 59.7% (37/62). The most frequent grade 1 AEs included fatigue 17% (9/53), fever 15% (8/53), injection site reaction 13.2% (7/53), and chills 9.4% (5/53). The most frequent grade 2 AEs were fatigue 33.3% (3/9) and generalized weakness 22.2% (2/9). Therapy was delayed by 2 wk because of the AEs possibly related to vaccine administration in 3 patients 1.4% (3/210). CONCLUSION: The present study demonstrates that the adverse events associated with COVID-19 vaccination are infrequent, mild, and rarely delay treatment in patients with solid tumors receiving systemic therapies.

Diagnostic Delay in Adolescents with Cancer During COVID-19 Pandemic: A New Price for Our Patients to Pay.

Worldwide, the coronavirus 19 disease pandemic caused a worse chance of a timely diagnosis for cancer patients. We conducted a retrospective analysis of new diagnoses registered in the national pediatric oncology database, comparing the first lockdown period (March-May 2020) with the same period of 2015-2019. The total number of cases (0-19 years) dropped by 20.8% (from 441 between 2015 and 2019 to 349 in 2020). A major reduction was observed for adolescents (15-19 years) (-32.9%) and for adolescents with solid tumors (-56.4%, p = 0.03). Our data suggest that the enforced lockdown reduced the possibility for these already vulnerable patients to access the referral centers.

SARS-CoV-2-specific immune responses in elderly and immunosuppressed participants and patients with hematologic disease or checkpoint inhibition in solid tumors: study protocol of the prospective, observational CoCo immune study.

BACKGROUND: Immunocompromised people (ICP) and elderly individuals (older than 80 years) are at increased risk for severe coronavirus infections. To protect against serious infection with SARS-CoV-2, ICP are taking precautions that may include a reduction of social contacts and participation in activities which they normally enjoy. Furthermore, for these people, there is an uncertainty regarding the effectiveness of the vaccination. The COVID-19 Contact (CoCo) Immune study strives to characterize the immune response to COVID-19 vaccination in immunocompromised, elderly people, and patients with hematological or oncological diseases. The study uses blood-based screenings to monitor the humoral and cellular immune response in these groups after vaccination. Questionnaires and qualitative interviews are used to describe the level of social participation. METHODS: The CoCo Immune Study is a mixed methods prospective, longitudinal, observational study at two large university hospitals in Northern Germany. Starting in March 2021, it monitors anti-SARS-CoV-2 immune responses and collects information on social participation in more than 600 participants, at least 18 years old. Inclusion criteria and subcohorts: Participants with (1) regularly intake of immunosuppressive medication (ICP-cohort) or (2) age ≥ 80 years (80 + -cohort). Additionally, patients with current or former (3) myeloid, (4) lymphatic disease or (5) solid tumor under checkpoint inhibition (3-5: HO-cohort). EXCLUSION CRITERIA: (1) refusal to give informed consent, (2) contraindication to blood testing, (3) inability to declare consent. Participants complete a questionnaire at four different time points: prior to full vaccination, and 1, 6 and 12 months after completed vaccination. In addition, participants draw blood samples themselves or through a local health care provider and send them with their questionnaires per post at the respective time points after vaccination. Patients of the HO cohort dispense additional blood samples at week 3 to 12 and at month 6 to 9 after 2nd vaccination to gain additional knowledge in B and T cell responses. Selected participants are invited to qualitative interviews about social participation. DISCUSSION: This observational study is designed to gain insight into the immune response of people with weakened immune systems and to find out how social participation is affected after COVID-19 vaccination. TRIAL REGISTRATION: This study was registered with German Clinical Trial Registry (registration number: DRKS00023972) on 30th December 2020.

Clinical Presentations and Outcomes of Coronavirus Disease 2019 in Patients With Solid Tumors.

Background Coronavirus disease 2019 (COVID-19) is a global health crisis. The literature suggests that cancer patients are more prone to be affected by COVID-19 because cancer suppresses the immune system and such patients usually present poor results. The objective of this study is to present all clinical, laboratory, and demographic characteristics of COVID-19 patients with solid tumors. Methodology This study was conducted at the Dow University of Health Sciences for a period of six months from April 2020 to September 2020. In this study, we included a total of 1,519 confirmed patients diagnosed with solid tumors via polymerase chain reaction. The mortality timeline within 30 days of contracting the virus was considered, and the median age of the included individuals was 61 years, with a range of 20-95 years. Of the patients included in the study, 49.4% (750) were men; moreover, 3.15% of our study population had prostate cancer, 10.20% had colorectal cancer, 2.76% had breast cancer, and 10.46% had lung cancer. Of the patients, 25.93% presented with at least one comorbidity. For 73% of the patients, at least one direct therapy for COVID-19 was included in the treatment; 56.6% of the patients were hospitalized, and 11.32% were admitted to the intensive care unit. Results The mortality rate was 4.74% in the first 30 days after diagnosis, where 72 patients died. The findings of the first multi-variation model showed that males at older ages who were diabetic and going through cytotoxic therapy were prone to die within the first 30 days. However, the 30-day mortality rate was lower in patients diagnosed with prostate and breast cancer. The second set incorporated laboratory factors, where we found that higher values of leukocytosis, thrombocytopenia, and lymphocytopenia were correlated with higher rates of mortality within 30 days. Conclusions We conclude that there is a higher mortality rate of COVID-19 in patients with solid tumors than in the general population. However, it was found to be lower in the Pakistani population compared with the Chinese and Western populations. Intensive care can decrease mortality rates in COVID-19 and cancer patients.

Patients with hematologic cancers are more vulnerable to COVID-19 compared to patients with solid cancers.

Previous studies reported that COVID-19 patients with cancer had higher rates of severe events such as intensive care unit (ICU) admission, mechanical ventilation (MV) assistance, and death during the COVID-19 course compared to the general population. However, no randomized study compared the clinical course of COVID-19 in patients with hematologic cancers to patients with solid cancers. Thus, in this study, we intend to reveal the outcome of COVID-19 in hematologic cancer patients and compare their outcomes with COVID-19 patients with solid cancers. The data of 926 laboratory-confirmed COVID-19 patients, including 463 hematologic cancer patients and an age-gender paired cohort of 463 solid cancer patients, were investigated retrospectively. The frequencies of severe and critical disease, hospital and ICU admission, MV assistance were significantly higher in hematologic cancer patients compared with the solid cancer patients (p = 0.001, p = 0.045, p = 0.001, and p = 0.001, respectively). The hospital stay was longer in patients with hematologic cancers (p = 0.001); however, the median ICU stay was 6 days in both groups. The case fatality rate (CFR) was 14.9% in patients with hematologic cancers, and it was 4.8% in patients with solid cancers, and there was a statistically significant difference regarding CFR between groups (p = 0.001). Our study revealed that COVID-19 patients with hematologic cancers have a more aggressive course of COVID-19 and have higher CFR compared to COVID-19 patients with solid cancers and support the increased susceptibility of patients with hematologic cancers during the outbreak.