COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223)

Supplementary Material for: Key prognostic factors create a composite risk score to stratify patients into high- and low treatment benefit groups: A multicenter, retrospective data analysis of 84 mCRC patients treated with regorafenib as part of the CORRECT and CONSIGN trials

Introduction: In further-line mCRC treatment, median progression-free survival (PFS) is rather short, and many patients do not benefit from any anti-tumor treatment and should therefore treated according to best-supportive care (BSC). A risk score based on standard laboratory values using markers of tumor inflammation aims to define a patient cohort with high treatment benefit and might offer insights into tumor biology. As regorafenib has been dropped off the German market due to an unfavorable risk-benefit ratio, patient selection is key for any further-line treatment option. Methods: We used cox regression analysis to determine lab markers that are independent prognostic factors of OS and PFS outcome. The influence of these variables was weighted using an estimator, which was calculated using cox regression analysis. The estimators were implemented as multiplication factors, resulting in a risk score. A cut-off value for the resulting risk values was then determined via cox regression analysis resulting in a low- and high-risk subgroup. Results: Using data of 82 patients, a risk score identifying long-term survival in patients with last line mCRC treatment could be calculated. The following parameters were associated with significantly longer survival in multivariate analysis: NLR ≤ 5 (p = 1.4) survived only 3.3 months after starting therapy with regorafenib (n=43, p<0.001, HR=3.76). Discussion/Conclusions: The presented composite risk score stratifies patients into two prognostic subgroups characterized by standard laboratory values. Patients with signs of systemic characterized by elevated NLR, AP, and CRP have a high composite risk score and a significant shorter overall survival. Although this score needs to be prospectively validated in larger cohorts, it may be used to stratify patients suitable for further-line treatment studies

Supplementary Material for: Key prognostic factors create a composite risk score to stratify patients into high- and low treatment benefit groups: A multicenter, retrospective data analysis of 84 mCRC patients treated with regorafenib as part of the CORRECT and CONSIGN trials

Introduction: In further-line mCRC treatment, median progression-free survival (PFS) is rather short, and many patients do not benefit from any anti-tumor treatment and should therefore treated according to best-supportive care (BSC). A risk score based on standard laboratory values using markers of tumor inflammation aims to define a patient cohort with high treatment benefit and might offer insights into tumor biology. As regorafenib has been dropped off the German market due to an unfavorable risk-benefit ratio, patient selection is key for any further-line treatment option. Methods: We used cox regression analysis to determine lab markers that are independent prognostic factors of OS and PFS outcome. The influence of these variables was weighted using an estimator, which was calculated using cox regression analysis. The estimators were implemented as multiplication factors, resulting in a risk score. A cut-off value for the resulting risk values was then determined via cox regression analysis resulting in a low- and high-risk subgroup. Results: Using data of 82 patients, a risk score identifying long-term survival in patients with last line mCRC treatment could be calculated. The following parameters were associated with significantly longer survival in multivariate analysis: NLR ≤ 5 (p = 1.4) survived only 3.3 months after starting therapy with regorafenib (n=43, p<0.001, HR=3.76). Discussion/Conclusions: The presented composite risk score stratifies patients into two prognostic subgroups characterized by standard laboratory values. Patients with signs of systemic characterized by elevated NLR, AP, and CRP have a high composite risk score and a significant shorter overall survival. Although this score needs to be prospectively validated in larger cohorts, it may be used to stratify patients suitable for further-line treatment studies