S281: prior exposure to immunosuppressive agents and comorbidities are associated with worse outcomes of sars-cov2 infection in ph-neg chronic myeloproliferative neoplasms: results of epicovideha survey

Background: Philadelphia-negative chronic myeloproliferative neoplasms (MPN) typically incur high rates of thrombosis and infections and cytoreductive drugs may modulate such risks. Aims: The present analysis aims at assessing the severity and outcomes of MPN facing coronavirus disease 2019 (COVID-19). Hence, we aimed to assess the impact of immunosuppressive agents and comorbidity burden in COVID-19 outcome. Methods: The EPICOVIDEHA registry is an online survey (www.clinicalsurveys.net) that has collected since April 2020 until January 2022 5,445 cases of COVID-19 in individuals with baseline haematological malignancies (Salmanton-García et al, 2021 Hemasphere) The survey is promoted by the European Hematology Association - Infectious Diseases Working Party (EHA-IDWP) and has been approved centrally by the Institutional Review Board and Ethics Committee of Fondazione Policlinico Universitario A. Gemelli – IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy (Study ID: 3226). Results: Overall, 308 patients (5.6%) with MPN were observed for a median of 102 days (IQR: 21-223, range 22-97) after COVID-19 diagnosis. Median age at infection was 69 years (IQR: 58-77, range 22-97) and at least one comorbidity was reported from most of the individuals (62.6%, n = 193). A large portion of patients had a history of cardiopathy (n=109, 35.4%), diabetes (n=40, 15.9%), or chronic pulmonary disease (n=44, 14.3%). Myelofibrosis (MF) (n=140, 45.4%) was the most prevalent baseline malignancy, with 18 MF patients (12.9%) reporting 3 or more comorbidities. Out of the whole cohort, 72 patients (42.8% of MF) received immunosuppressige therapies including steroids, immunomodulatory drugs (IMiDs) or JAK-inhibitors. Hospitalization and consecutive admission to intensive care unit was required for 187 (60.7%) and 45 (24%) patients, respectively. At multivariate logistic regression, hospital admission was predicted by age ≥70 years (OR 2.809; 95% CI 1.651-4.779), exposure to immunosuppressive therapies (OR 2.802; 95% CI 1.5380-5.103) and comorbidity burden. During the study follow-up (median 101 days; range 21-222) 84 patients deceased after a median time of 14 days (IQR: 8-49, range 0-457) since COVID-19 diagnosis. The fatality rate (FR) decreased from 40.3% (50 out of 124) in the first two quarters of year 2020 to 15.8% (3 out of 19) in the first two quarters of year 2021 (p<0.05). Death was principally attributable to COVID-19 in 58 patients (69.0%) and contributable by COVID-19 in 15 (17.9%). FR was particularly high (54 out of 140, 38.6%) in MF patients and in patients receiving immunosuppressive agents (32 out of 86, 37%). Moreover, FR increased from 13.0% in individuals with no comorbidity to 36.0% and 62.1% in those with ≥2 or ≥3 comorbidities, respectively. More specifically, three comorbidities independently increased the FR: chronic cardiopathy (HR 1.653; 95%CI 1.017-2.687), chronic pulmonary disease (HR 1.847; 95% CI 1.097-3.109), and diabetes mellitus (HR 1.712; 95% CI 1.006-2.914). A heavy comorbidity burden, namely 3 or more comorbidities (HR 2.956; 95% CI 1.403-6.227), advanced age, namely ≥70 years (HR .809; 95% CI 1.651-4.779), myelofibrosis (HR 2.501; 95% CI 1.384-4.519), and ICU admission (HR 2.669; 95% CI 1.641-4.342) independently predicted FR. Image:Summary/Conclusion: COVID-19 infection led to a particularly dismal outcome in patients exposed to immunosuppressive agents and in those with chronic heart or pulmonary diseases, or diabetes. These data allow to tailor future strategies for preventing severe COVID-19 in MPN patients.