Sars-Cov-2 Omicron (B11529) Variant Infection Leads to High Morbidity and Mortality in Unvaccinated Patients with Cancer

Background: The Omicron (B.1.1.529) SARS-CoV-2 variant is highly transmissible and escapes vaccinal immunity. Evidence is lacking as to the impact of Omicron in oncological patients. Method(s): Capitalizing on OnCovid study data (NCT04393974), we analysed COVID-19 morbidity and case fatality rate at 28 days (CFR28) of unvaccinated patients across 3 phases defined following the evolution of the pandemic in Europe, according to date of COVID-19 diagnosis: "Pre-vaccination" phase (27/02/2020-30/11/2020), "Alpha- Delta variant" phase (01/12/2020-14/12/2021), "Omicron variant" phase (15/12/2021-31/01/2022). Finding(s): By the data lock of 04/02/2022, 3820 patients from 37 institutions across 6 countries were entered. Out of 3473 eligible patients, 2033 (58.6%), 1075 (30.9%) and 365 (10.5%) were diagnosed during the Pre-vaccination, Alpha-Delta and Omicron phases. In total 659 (61.3%) and 42 (11.5%) were unvaccinated in the Alpha-Delta and Omicron. Unvaccinated patients across the Omicron, Alpha-Delta and Pre-vaccination phases experienced similar CFR28 (27.5%, 28%, 29%, respectively). Following propensity score matching, 42 unvaccinated Omicron patients were matched with 122 and 121 patients from the Pre-vaccination and Alpha-Delta phases respectively, based on country of origin, sex, age, comorbidity burden, primary tumour, cancer stage and status, and the receipt of systemic anticancer therapy at COVID-19. Unvaccinated Omicron patients experienced improved COVID-19 outcomes in comparison to patients diagnosed during the Prevaccination phase. Morbidity and mortality were comparable to those of unvaccinated patients diagnosed during the Alpha-Delta phase. Interpretation(s): Despite time-dependent improvements in outcomes reported in the Omicron phase, patients with cancer remain highly vulnerable to SARS-CoV-2 in absence of vaccinal protection. This study provides unequivocal evidence in support of universal vaccination of patients with cancer as a protective measure against morbidity and mortality from COVID-19.

Clinical assessment of the Omicron outbreak in Europe and trends in morbidity and mortality from COVID-19 and cancer

Background: Whilst patients (pts) with cancer are at increased risk of adverse outcome from Coronavirus disease 2019 (COVID-19), no evidence exists as to the natural history of the SARS-CoV-2 B.1.1.529 (Omicron) variant in this population. Methods: Capitalizing on OnCovid study data (NCT04393974), a European registry that collects data on consecutive patients with cancer and COVID-19, we analysed COVID-19 morbidity and case fatality rates at 14 days (CFR14) across 3 phases defined following the evolution of the pandemic in Europe, according to date of COVID-19 diagnosis: “Pre-vaccination” phase (27/02/2020-30/ 11/2020), “Alpha-Delta variant” phase (01/12/2020-14/12/2021), “Omicron variant” phase (15/12/2020-31/01/2022). Results: By the data lock of 04/02/2022, 3820 consecutive pts were enrolled, 3473 of whom were eligible for this analysis. Among them, 2033 (58.6%), 1075 (30.9%) and 365 (10.5%) were diagnosed during the Pre-vaccination, Alpha-Delta and Omicron phases. Pts diagnosed in the Omicron phase were more likely aged < 65 years (48.6% vs 42.5%, 39.4% p = 0.01), had < 2 comorbidities (61.9% vs 55.6%, 52.1% p = 0.01). They had more advanced-stage tumours (62.1% vs 53.3%, 49.0%, p < 0.01) and were more likely receiving systemic anticancer therapy (SACT) at COVID-19 diagnosis (54.9% vs 43.9%, 39.6%, p < 0.01). Proportions of fully vaccinated/boosted pts were higher in the Omicron phase (33.9%-48.1%) compared to the Alpha-Delta phase (16.6%-2.3%, p < 0.01). Pts diagnosed in the Omicron phase had improved CFR14 (9.0% vs 13.9%, 23.1%, p < 0.01) lower hospitalization rates due to COVID-19 (24.4% vs 41.4%, 56.6%, p < 0.01), lower complications rates (15.3% vs 33.6%, 39.4%, p < 0.01) and reduced need for COVID-19 specific therapy (22.4% vs 43.0%, 65.7% p < 0.01) compared to the Alpha-Delta and pre-vaccinal phase. After adjusting for country of origin, sex, age, comorbidities, tumour stage, status and receipt of SACT at COVID-19, patients diagnosed in the Omicron phase displayed the lowest risk of death at 14 days compared to earlier phases. Similarly, rates of hospitalization and complicated COVID-19 were lowest for Omicron phase. Conclusions: This is the first study to portray the evolution of the SARS-CoV-2 Omicron outbreak in Europe, documenting an improvement in all COVID-19 outcomes compared to earlier phases of the pandemic. Enhanced healthcare capacity, improved disease management, immunization campaigns alongside differential virulence of viral strains are likely contributing to improved outcomes across phases.

Long-term benefit of lurbinectedin as palliative chemotherapy in progressive malignant pleural mesothelioma (MPM): final efficacy and translational data of the SAKK 17/16 study.

BACKGROUND: The SAKK 17/16 study showed promising efficacy data with lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma. Here, we evaluated long-term outcome and analyzed the impact of lurbinectedin monotherapy on the tumor microenvironment at the cellular and molecular level to predict outcomes. MATERIAL AND METHODS: Forty-two patients were treated with lurbinectedin in this single-arm study. Twenty-nine samples were available at baseline, and seven additional matched samples at day one of cycle two of treatment. Survival curves and rates between groups were compared using the log-rank test and Kaplan-Meier method. Statistical significance was set at P value <0.05. RESULTS: Updated median overall survival (OS) was slightly increased to 11.5 months [95% confidence interval (CI) 8.8-13.8 months]. Thirty-six patients (85%) had died. The OS rate at 12 and 18 months was 47% (95% CI 32.1% to 61.6%) and 31% (95% CI 17.8% to 45.0%), respectively. Median progression-free survival was 4.1 months (95% CI 2.6-5.5 months). No new safety signals were observed. Patients with lower frequencies of regulatory T cells, as well as lower tumor-associated macrophages (TAMs) at baseline, had a better OS. Comparing matched biopsies, a decrease of M2 macrophages was observed in five out of seven patients after exposure to lurbinectedin, and two out of four patients showed increased CD8+ T-cell infiltrates in tumor. DISCUSSION: Lurbinectedin continues to be active in patients with progressing malignant pleural mesothelioma. According to our very small sample size, we hypothesize that baseline TAMs and regulatory T cells are associated with survival. Lurbinectedin seems to inhibit conversion of TAMs to M2 phenotype in humans.

EuroNet MRPH: Networking Opportunities for Public Health Medical Residents

Background The European Network of Medical Residents in Public Health (EuroNet MRPH) is a non-profit, international, independent and non-governmental network of national associations of public health residents around Europe. Objectives To describe the results accomplished by EuroNet MRPH and to show networking opportunities provided to medical residents in public health (MRPH) from 2011 to 2021. Results EuroNet's mission is to improve and facilitate connection between MRPH, to promote pan-European Research, and to facilitate international mobility. Digital and quarterly face-to-face meetings are used as a way of communication. Since 2011, 10 European MRPH associations and 4 individual members have joined the network, representing the UK, France, Spain, Italy, Portugal, Ireland, the Netherlands, Croatia, Slovenia, Turkey, Malta, Poland, Bosnia and Herzegovina, and Austria. In this period, 27 face-to-face meetings have been organised, promoting cooperation and exchanging of ideas between MRPH. Moreover, three working groups (WG) have been established, focusing on research, internships, and communication. Regarding research, studies about e-cigarettes, conflicts of interest, and the impact of COVID-19 on mental health of MRPH have been conducted. When it comes to internships, more than 20 possible destinations and an online form are available on our website, providing MRPH information and support. Finally, thanks to the communication WG, 20 newsletters have been published, sharing experiences and thoughts from members of the network. Moreover, EuroNet has an established presence in social media, with active accounts in Twitter, Instagram and Facebook, where public health information and opportunities for young professionals are promoted. Conclusions In the last ten years, EuroNet MRPH has actively promoted networking opportunities among European Medical Residents in Public Health. Key messages Enhancing international cooperation among young public health professionals is fundamental in order to face current and future public health challenges. EuroNet MRPH represents a useful tool to promote collaboration among young public health professionals.

Influenza surveillance system and Covid-19

The clinical presentation of symptomatic SARS-CoV-2 not only includes viral pneumonia, but also milder illness overlapping with influenza-like illness (ILI), allowing a potential tracking of the infection in the framework of the national influenza surveillance system (SS). By comparing the data recorded by the influenza SS in 2019-20 season to those collected for the previous years, we want to evaluate whether the implementation of ILI SS could succeed in early detection and monitoring of Covid-19 diffusion. We analyzed the data recorded by the influenza SS and we compared the distribution of ILI incidence rate by week for 2017-18, 2018-19 and 2019-20 season in order to understand whether the SS detected any abnormality coinciding with Covid-19 outbreak. The distribution of ILI cases in the three seasons presented a similar pattern up to the 9th week;after then, a reduction in the ILI incidence rate was observed in the 2017-18 and the 2018-19 season while an increase was detected for 2019-20. During 2019-20 season, three major characteristics stand out: i) at the beginning of Covid-19 epidemic (7th-9th week) 9,17/1000 cases were reported;ii) during the recognition of the COVID-19 outbreak (9th-10th week) 6,36/1000 cases;iii) during the spread of Covid-19 (10th-11th week) an unexpected increase to 7,72/1000 cases. Additionally, their geographical distribution was concentrated in the areas known to be most affected by the epidemic. The influenza SS enabled us to detect the introduction and distribution of COVID-19. Implementation of the system should be prioritized in order to early identify new waves of Covid-19 but also any future novel respiratory pathogen. In order to empower the SS, it would be advisable to increase the population coverage about 2% which is the actual standard. Key messages The influenza surveillance system detected the first wave of Covid-19 in Lombardy Region, Italy. The influenza surveillance system should be implemented in order to bring a benefit both to the current situation and in sight of future public health challenges.

Thoracic cancers international COVID-19 collaboration (TERAVOLT): Small-cell lung cancer andother rare thoracic malignancies

Background: At the last update of the TERAVOLT registry, patients with thoracic malignancies and COVID-19showed a high mortality rate (35.5% overall and 31% due to COVID-19) compared to the general population and toother solid tumors. Major determinants of mortality were age, Eastern Cooperative Oncology Group PerformanceStatus (ECOG-PS), and previous administration of chemotherapy. No cancer-specific data are available with respectto small-cell lung cancer (SCLC) and other rare thoracic malignancies. Methods: TERAVOLT is an international, multicenter observational registry launched to collect data on patients withthoracic malignancies diagnosed with COVID-19 infection. Risk factors for hospitalization and mortality wereidentified by Wilcoxon rank sum tests (continuous variables) or χ2 tests (categorical variables). Here we present thesubgroup analyses of SCLC and other rare thoracic malignancies, including malignant pleural mesothelioma (MPM), thymic carcinoma/thymoma, and carcinoid/neuroendocrine lung tumors. Results: As of June 4th, 2020, a total of 581 patients with COVID-19 and thoracic cancers have been entered;among them, 66 (11%) were SCLC, 22 (4%) were MPM, 18 (3%) were thymic carcinoma/thymoma, 12 (2%) werecarcinoid/neuroendocrine lung tumors, and 442 (76%) NSCLC;21 were an unknown type. Among SCLC patients,54% were > 65 years old, 56% were males, 98% were current/former smokers, 31% had an ECOG-PS ≥ 2, 67%had stage IV disease, 82% were on current oncologic treatment at the COVID-19 diagnosis, and 58% werereceiving chemotherapy alone or in combination with immune checkpoint inhibitors. Among other non-NSCLCpatients, 56% were > 65 years old, 56% were males, 69% were current/former smokers, 24% had an ECOG-PS ≥ 2,50% had stage IV disease, 52% were on current oncologic treatment at the COVID-19 diagnosis, and 37% werereceiving chemotherapy alone or in combination with immune checkpoint inhibitors. Overall, 79.7% of the patientsrequired hospitalization, 15.4% were admitted to an ICU, and 39.8% died (36.2% due to COVID-19). Among SCLCpatients, 74.2% required hospitalization, 14.3% were admitted to an ICU, and 42.2% died (37.5% due to COVID-19).Among SCLC patients, age > 65 years old (p=0.81), gender (p=0.71), smoking status (p=1.0), ECOG-PS ≥2(p=0.17), disease stage of IV (p=0.37), and having received chemotherapy alone or with checkpoint inhibitors(p=0.84) were not associated with mortality. Conclusions: This analysis confirmed that patients with thoracic malignancies have a high mortality and risk forhospitalization due to COVID-19 overall. SCLC patients showed the highest mortality rate among thoracic cancerpatients.

Influenza-like illness and SARS-Cov-2 in the multicenter, prospective, observational INVIDIa-2 study (INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors: A transversal challenge): A FICOG study

Background: The susceptibility of advanced cancer patients treated with immune checkpoint inhibitors (ICI) for viral infections has not been investigated. Currently, there are no robust data supporting the efficacy, safety and recommendation for influenza vaccination in cancer patients receiving ICI. Methods: The prospective, multicenter, observational INVIDIa-2 study investigated the clinical efficacy of influenza vaccination in advanced cancer patients with solid tumors receiving ICI between October 2019 and January 2020. The incidence of influenza-like illness (ILI, primary endpoint) was observed until April 30, 2020. Secondary endpoints included a non-prespecified analysis for COVID-19. Results: The study enrolled 1279 patients;1188 were evaluable. Of them, 11 patients developed ILI symptoms with confirmed diagnosis of COVID-19 (incidence of 0.9% and lethality of 72%, irrespective of the flu vaccination). Of the remaining 1177 patients, 574 received flu vaccination (48.8%). The ILI incidence was 7.7% (91 patients of 1177). Patients receiving the flu vaccine were significantly more frequently elderly (p<0.0001), former or active smokers (p<0.0001), affected by lung cancer (p=0.017) and by non-cancer comorbidities (p<0.0001) when compared to unvaccinated patients. The flu vaccine did not prevent ILI in the study population, irrespective of the vaccine type (quadrivalent vs trivalent, adjuvated vs non): the incidence of ILI was 8.2% in vaccinated vs 7.3% in unvaccinated patients (p=0.57). ILI complications were significantly less frequent for patients receiving flu vaccine (12.8% vs 40.9%, p=0.002). Hospital admission due to ILI occurred for 10 patients (11% of ILI cases;7 were unvaccinated). The ILI lethality was 2.2% (2 of 91 patients, both unvaccinated). Among vaccinated patients, those receiving adjuvated vaccines had lower incidence of ILI (4.8% vs 9.9%, p=0.046). Conclusions: Flu vaccination was not effective for ILI prevention, nor for COVID-19. Nevertheless, it reduced ILI complications, with no ILI-related deaths in vaccinated patients. We recommend the vaccine in ICI-treated cancer patients. Clinical trial identification: Eudract number of the trial: 2020-002603-18. Legal entity responsible for the study: FICOG Federation of Italian Cooperative Oncology Groups. Funding: FICOG (Federation of Italian Cooperative Oncology Groups, promoter and main sponsor), in turn funded by Seqirus UK and Roche S.p.A. for the present study. Disclosure: M. Bersanelli: Research grant/Funding (self), Research grant/Funding (institution), for the present study: Seqirus and Roche;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses, for other activities outside the present study: Pfizer, BMS, Novartis. S. Buti: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers Squibb (BMS), Pfizer;MSD, Ipsen, Roche, Eli-Lilly, AstraZeneca and Novartis. U. De Giorgi: Research grant/Funding (institution): AstraZeneca, Roche, Sanofi;Honoraria (self): Astellas, Bayer, BMS, Ipsen, Janssen, Merck, Pfizer, Sanofi. P. Bonomo: Honoraria (self): Merck Serono, Angelini Pharma,. All other authors have declared no conflicts of interest.