Chemotherapy-induced febrile neutropenia (FN) in the US: healthcare resource utilization (HCRU) and costs (preprint)

Purpose Febrile neutropenia (FN) is a known side effect of chemotherapy, often requiring hospitalization. Economic burden increases with an FN episode and estimates of cost per episode should be updated from real-world data.Methods A retrospective claims analysis of FN episodes in patients with non-myeloid malignancies from 2014 to 2021 was performed in IQVIA PharMetrics® Plus database. FN episodes were defined as having same-day claims for neutropenia and fever or infection, plus antibiotic in outpatient settings, following a claim for chemotherapy; index date was defined as the first claim for neutropenia/fever/infection. Patients receiving bone marrow/stem cell transplant and CAR-T therapy were excluded, as were select hematologic malignancies or COVID-19. Healthcare utilization and costs were evaluated and described overall, by episode type (w/wo hospitalization), index year, malignancy type, NCI comorbidity score, and age group.Results 7,033 FN episodes were identified from 6,825 patients. Most episodes had a hospitalization (91.2%) and 86% of patients had ≥ 1 risk factor for FN. Overall, FN episodes had a mean (SD) FN-related cost of $25,176 ($39,943). Episodes with hospitalization had higher average FN-related costs versus those without hospitalization ($26,868 vs $7,738), and costs increased with comorbidity score (NCI = 0: $23,095; NCI > 0–2: $26,084; NCI ≥ 2: $26,851).Conclusions FN continues to be associated with significant economic burden, and varied by cancer type, comorbidity burden, and age. In this analysis, most FN episodes were not preceded by GCSF prophylaxis. The results of this study highlight the opportunity to utilize GCSF in appropriate oncology scenarios.

Prognostic factors registered on admission to the hospital related to mortality risk in cancer patients with COVID-19: a retrospective cohort study (preprint)

Background: Cancer patients are a particularly vulnerable risk group of the severe course of COVID-19 due to, i.e. suppression of the immune system. The study aimed to find links between parameters registered on admission to the hospital, and the risk of latter death in oncology patients with COVID-19. Design: Retrospective cohort study. Methods: The study included patients with a reported history of malignant tumor (N=151) and the control group with no history of cancer (N=151) hospitalized due to COVID-19 between March 2020 and August 2021. The variables registered on admission were divided into categories for which we calculated the multivariate Cox proportional hazards models. Results: The median age of the study group was 68 years (min-max: 17-95). 50.33% (76/151) were women. Multivariate Cox proportional hazards models were successfully obtained for the following categories: Patient data, Comorbidities, Signs recorded on admission, Medications used before hospitalization and Laboratory results recorded on admission. With the models developed for oncology patients, we identified the following variables that registered on patients’ admission were linked to significantly increased risk of death: male sex, presence of metastases in neoplastic disease, impaired consciousness (somnolence or confusion), wheezes/rhonchi, the levels of white blood cells and neutrophiles. Conclusion: Identifying the predictors of a poorer prognosis may serve clinicians in better tailoring treatment among cancer patients with COVID-19. Our results can help develop prognostic models or compare the results of other studies, which will translate into better treatment management and better prognosis in this group of patients.

Clinical prediction rules for adverse outcomes in patients with SARS COV-2 infection by the omicron variant (preprint)

Background: Factors related to an adverse evolution in COVID19 infection are needed for proper decision making. We try to identify factors related to hospitalization, ICU admission, and mortality related to the infection. Methods. Retrospective cohort study of patients with SARS-CoV-2 infection from March 1st 2020 to January 9th 2022. The sample was randomly divided into two subsamples, for the purposes of derivation and validation of the prediction rule, until omicron variant appearance and afterwards, respectively. Data collected for this study included sociodemographic data, baseline comorbidities and treatments, and other background data. Multivariable logistic regression models using Lasso logistic regression were used . Results. In the multivariable models, older age, male, peripheral vascular disease, heart failure, heart disease, cerebrovascular, dementia, liver, kidney, diabetes, hemiplegia, interstitial pulmonary disease, cystic fibrosis, malignant tumors, as well as diuretics and the chronic systemic use of steroids were common predictive factors of death. Similar predictors, except liver disease, plus arterial hypertension, were also related to adverse evolution. Similar predictors to the previous, including liver disease, plus dyslipidemia, inflammatory bowel disease, respiratory diseases, and the basal prescription of NSAIDs, heparin, bronchodilators, or immunosuppressants were related to hospital admission. All risk scores developed had AUCs from 0.79 (hospital admission) to 0.94 (death) in the validation in the omicron sample. Conclusions. We propose three risk scales for adverse outcomes and hospital admission easy to calculate and with high predictive capacity, which also work with the current omicron variant, which can help manage patients in primary, emergency, and hospital care.

Adequate Immunogenicity And Low Rate of Severe Adverse Events After SARS-CoV-2 mRNA-Based Vaccination In Patients With Solid Malignancies On Active Treatment Starts To Decline 3 Months After Complete Primary Course of Vaccination (preprint)

Background: SARS-CoV-2 vaccination in cancer patients is crucial since they are at increased risk of severe COVID-19 disease course, but data on efficacy and safety of vaccination are scarce. Methods: : We performed a prospective observational study of patients with solid cancers on active anticancer treatment (chemotherapy, immunotherapy with immune checkpoint inhibitors (ICI) or targeted therapy) that received mRNA-based SARS-CoV-2 vaccination at two institutions in Slovenia. The immunogenicity was assessed by the detection of anti-SARS-CoV-2 S1 IgG antibodies in serum; patients were sampled before, 2-3 weeks after the first dose, 2-3 weeks after the second dose, and 3 months after the complete primary course of vaccination. The results were also compared to controls, sampled at similar time points. Results: : Between March and July 2021 112 patients were included in the analysis. The seroconversion rate in patients without prior COVID-19 infection was 96% after the complete primary course of vaccination with 2 doses, compared to 100% for healthy controls. The seroconversion rate after vaccination for patients on chemotherapy, ICI, and targeted therapy was 100%, 91%, and 97%, respectively. All controls and the majority of patients on chemotherapy and targeted therapy, but only 83% for patients on ICI were adequate responders (anti-SARS-CoV-2 S1 IgG ≥ 880 ng/ml). Three months after the vaccination, a significant drop in antibody levels was observed in patients receiving ICI compared to controls ( P < 0.001). Adverse events were mostly mild and predictable, none of the patients experienced serious adverse events after vaccination. Conclusions: : Immunogenicity after mRNA-based vaccination against SARS-CoV-2 in cancer patients is only slightly impaired, but influenced by the type of anticancer therapy received. Patients on ICI have the slightest and gradual antibody production. Since antibody levels decline after three months, a third vaccination dose is reasonable to provide adequate protection against severe COVID-19 disease course.The study was approved by the National Ethics Committee (No. 0120-39/2021/6)

Interim results of the safety and immune-efficacy of 1 versus 2 doses of COVID-19 vaccine BNT162b2 for cancer patients in the context of the UK vaccine priority guidelines (preprint)

ABSTRACT Background The efficacy and safety profile of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been definitively established in immunocompromised patient populations. Patients with a known cancer diagnosis were hitherto excluded from trials of the vaccines currently in clinical use. Methods This study presents data on the safety and immune efficacy of the BNT162b2 (Pfizer-BioNTech) vaccine in 54 healthy controls and 151 mostly elderly patients with solid and haematological malignancies, respectively, and compares results for patients who were boosted with BNT162b2 at 3 weeks versus those who were not. Immune efficacy was measured as antibody seroconversion, T cell responses, and neutralisation of SARS-CoV-2 Wuhan strain and of a variant of concern (VOC) (B.1.1.7). We also collected safety data for the BNT162b2 vaccine up to 5 weeks following first dose. Findings The vaccine was largely well tolerated. However, in contrast to its very high performance in healthy controls (>90% efficacious), immune efficacy of a single inoculum in solid cancer patients was strikingly low (below 40%) and very low in haematological cancer patients (below 15%). Of note, efficacy in solid cancer patients was greatly and rapidly increased by boosting at 21-days (95% within 2 weeks of boost). Too few haematological cancer patients were boosted for clear conclusions to be drawn. Conclusions Delayed boosting potentially leaves most solid and haematological cancer patients wholly or partially unprotected, with implications for their own health; their environment and the evolution of VOC strains. Prompt boosting of solid cancer patients quickly overcomes the poor efficacy of the primary inoculum in solid cancer patients. RESEARCH IN CONTEXT Evidence before this study Some cancer patients have been shown to exhibit sustained immune dysregulation, inefficient seroconversion and prolonged viral shedding as a consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Consequently, their exclusion and, in particular, the exclusion of patients receiving systemic anti-cancer therapies, from the registry trials of the 5 approved COVID-19 vaccines raises questions about the efficacy and safety of SARS-CoV-2 vaccination in this patient population. In addition, whilst the change in the UK’s dosing interval to 12-weeks aimed to maximise population coverage, it is unclear whether this strategy is appropriate for cancer patients and those on systemic anti-cancer therapies. Added value of this study We report that the RNA-based SARS-CoV-2 BNT162b2 vaccine administered in cancer patients was well tolerated, and we provide first insights into both antibody and T cell responses to the vaccine in an immunocompromised patient population. Implications of all the available evidence In cancer patients, one dose of 30ug of BNT162b2 yields poor vaccine efficacy, as measured by seroconversion rates, viral neutralisation capacity and T cell responses, at 3- and 5-weeks following the first inoculum. Patients with solid cancers exhibited a significantly greater response following a booster at 21-days. These data support prioritisation of cancer patients for an early (21-day) second dose of the BNT162b2 vaccine. Given the globally poor responses to vaccination in patients with haematological cancers, post-vaccination serological testing, creation of herd immunity around these patients using a strategy of ‘ring vaccination’, and careful follow-up should be prioritised.