Changes in anticancer treatment plans in patients with solid cancer hospitalized with COVID-19: analysis of the nationwide BSMO-COVID registry providing lessons for the future.

BACKGROUND: Solid cancer is an independent prognostic factor for poor outcome with COVID-19. As guidelines for patient management in that setting depend on retrospective efforts, we here present the first analyses of a nationwide database of patients with cancer hospitalized with COVID-19 in Belgium, with a focus on changes in anticancer treatment plans at the time of SARS-CoV-2 infection. METHODS: Nineteen Belgian hospitals identified all patients with a history of solid cancer hospitalized with COVID-19 between March 2020 and February 2021. Demographic, cancer-specific and COVID-specific data were pseudonymously entered into a central Belgian Society of Medical Oncology (BSMO)-COVID database. The association between survival and primary cancer type was analyzed through multivariate multinomial logistic regression. Group comparisons for categorical variables were carried out through a Chi-square test. RESULTS: A total of 928 patients were registered in the database; most of them were aged ≥70 years (61.0%) and with poor performance scores [57.2% Eastern Cooperative Oncology Group (ECOG) ≥2]. Thirty-day COVID-related mortality was 19.8%. In multivariate analysis, a trend was seen for higher mortality in patients with lung cancer (27.6% versus 20.8%, P = 0.062) and lower mortality for patients with breast cancer (13.0% versus 23.3%, P = 0.052) compared with other tumour types. Non-curative treatment was associated with higher 30-day COVID-related mortality rates compared with curative or no active treatment (25.8% versus 14.3% versus 21.9%, respectively, P < 0.001). In 33% of patients under active treatment, the therapeutic plan was changed due to COVID-19 diagnosis, most frequently involving delays/interruptions in systemic treatments (18.6%). Thirty-day COVID-related mortality was not significantly different between patients with and without treatment modifications (21.4% versus 20.5%). CONCLUSION: Interruption in anticancer treatments at the time of SARS-CoV-2 infection was not associated with a reduction in COVID-related mortality in our cohort of patients with solid cancer, highlighting that treatment continuation should be strived for, especially in the curative setting.

Limited T cell response to SARS-CoV-2 mRNA vaccine among patients with cancer receiving different cancer treatments.

INTRODUCTION: Patients with cancer (PC) are at high risk of acquiring COVID-19 and can develop more serious complications. Deeper understanding of vaccines immunogenicity in this population is crucial for adequately planning vaccines programs. The ONCOVac study aimed to comprehensively assess the immunogenicity of mRNA-1273 vaccine in terms of humoral and cellular response. METHODS: We conducted a prospective, single-center study including patients with solid tumours treated with cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i), immunotherapy (IT) or chemotherapy (CT). Patients were enrolled previously to vaccination with mRNA-1273. We also involved health care workers (HCW) to serve as a control group. We took blood samples before first dose administration (BL), after first dose (1D), and after second dose (2D). The primary objective was to compare the rate and magnitude of T cell response after second dose whereas safety and humoral response were defined as secondary objectives. We also collected patient reported outcomes after both the first and second vaccine dose and a six-month follow-up period to diagnose incident COVID-19 cases was planned. RESULTS: The rate of specific anti-S serologic positivity (anti-S IgG cut-off point at 7,14 BAU/mL) was significantly higher in HCW compared to PC after 1D (100% versus 83.8%; p = 0.04), but similar after 2D (100% versus 95.8%; p = 0.5). This difference after 1D was driven by PC treated with CT (100% versus 64.5%; p = 0.001). Cellular response after 2D was significantly lower in PC than in HCW for both CD4+ (91.7% versus 59.7%; p = 0.001) and CD8+ (94.4% versus 55.6%; p < 0.001) T cells. We found a difference on pre-existing CD4+ T cell response in HCW comparing to PC (36% and 17%, p = 0.03); without difference in pre-existing CD8+ T cell response (31% and 23%, p = 0.5). After excluding patients with pre-existing T cell response, PC achieved even lower CD4+ (50.9% versus 95.5%, p < 0.001) and CD8+ (45.5% versus 95.5%, p < 0.001) T cell response compared with HCW. Regarding safety, PC reported notably more adverse events than HCW (96.6% versus 69.2%, p < 0.001). CONCLUSION: We demonstrated that PC showed a similar humoral response but a lower T cell response following two doses of mRNA-1273 vaccination. Further studies are needed to complement our results and determine the implication of low T cell response on clinical protection of PC against COVID-19.

Ninety-day mortality and clinical outcomes of patients with solid tumours and COVID-19 infection during the first pandemic outbreak in Catalonia, Spain: A multicentre retrospective study.

To describe the clinical outcomes and risk factors for 90-day mortality in patients with solid tumours (ST) and coronavirus disease 2019 (COVID-19) during the first outbreak in Catalonia. This is a multicentre retrospective study including adults with ST and COVID-19 confirmed by real time reverse transcription polymerase chain reaction between 13 March and 30 April 2020. Clinical and survival data were collected. Follow-up ended on 30 July 2020. Multivariate and survival analysis were performed. A hundred and fifteen patients were included. In all, 42.6% had advanced disease and were receiving anticancer treatment; 7% were admitted to the ICU and 22.6% died during hospitalisation. Thirty-day mortality was 27.8%, which increased to 33.9% at 90 days. Ninety-day mortality was associated with current smoker status (hazard ratio [HR]: 2.91, 95% CI [confidence interval]: 1.03-8.33, P = .044), baseline ECOG-PS 2 to 3 (HR: 3.88, 95% CI: 1.77-8.46, P < .001]), dyspnoea (HR: 3.02, 95% CI: 1.31-6.96, P = .009), a respiratory rate ≥ 24 (HR: 2.24, 95% CI: 1.02-4.92, P = .046) and sepsis (HR: 3.97, 95% CI: 1.78-8.88, P < .001). Of the 76 survivors, 73.6% had a follow-up visit. Of those, 33.9% had their cancer controlled and 23.2% had progressed. Thirty-five survivors were receiving anticancer treatment before COVID-19 diagnosis though 14 had to discontinue the treatment. Eight survivors without previous anticancer therapy started therapy. The median time to start anticancer therapy after COVID-19 was 45 days (interquartile range: 28-61). In conclusion, 90-day mortality in patients with ST and COVID-19 was 33.9%; current smoker status, poor ECOG-PS, dyspnoea, respiratory rate ≥24 and sepsis were independent risk factors for mortality; and survivors did not restart their anticancer treatment until 1.5 months after COVID-19 diagnosis.