Covid-19 in patients with chronic myeloid leukemia: Poor outcomes for patients with comorbidities, older age, advanced phase disease, and those from low-income countries: An update of the candid study

ABSTRACT

Background The iCMLf CANDID study represents the largest global cohort study to date characterizing COVID-19 in CML. This real world data collection, from 157 institutions in 49 countries, is essential to differentiate impact of patient, disease, and therapy specific factors on risk and outcomes, as the pandemic continues. Objective The primary aim of the CANDID study is to collect and analyze information on COVID-19 cases among CML patients (pts) to define risk factors, clinical evolution and outcome. Patients and methods Since March 2020, the iCMLf has collected data, with contributions from physicians treating CML pts and partner organizations. Country income was determined according to the World Bank Data. COVID-19 severity was classified according to the World Health Organization criteria. Univariate analysis was performed using log-rank test or logistic regression. Multivariate analysis was performed using Cox proportional hazards model or multivariate logistic regression. All the statistical analysis was performed using R statistical software (version 4.0.2). Results By April 2021, 642 cases of COVID-19 were reported from 50 countries. COVID-19 was diagnosed by PCR and/or serology in 601 pts (94%) and clinically suspected in 41 pts (6%). These 642 pts were reported by 186 physicians managing an estimated 37,449 CML pts (approximate incidence 0.7%). Most cases reported were from Europe (52%), followed by Asia (18%) and South America (16%). North America reported 10% of the cases and Africa 2.8%. The median age at the time of COVID-19 diagnosis was 53 years (18-94) and 59% of pts were males. Median time from CML diagnosis to COVID-19 was 8.34 years (range 0-34). CML treatment at the time of COVID-19 diagnosis hydroxyurea in 4 pts (6%), 38 (6%) bosutinib, 96 (15%) dasatinib, 275 (43%) imatinib, 92 (14%) nilotinib, 18 (3%) ponatinib, 3 (0.5%) other 4th generation TKIs;one alpha interferon. Ninety-nine (15%) pts were not receiving any treatment 53 (8%) were in treatment free-remission (TFR) and 46 were without treatment (7%) for other reasons treatment side effects (7), stem cell transplantation (12), pregnancy (3), lack of efficacy (2), unknown (1) and newly diagnosed CML (21). Significant comorbidities were present in 281 pts (44%), most common were heart conditions, including hypertension (162), diabetes (76), lung diseases (47) obesity (42) and others (84). COVID-19 was asymptomatic in 53 cases (8%), mild in 363 cases (56%), moderate in 119 cases (18%), severe/critical in 86 cases (13%) and of unknown severity in 21 cases (3%). At the data cut-off, from the 606 pts with known outcome, 48 pts died (8%) and 558 (92%) recovered. Age >75y (Fig 1A, p<0.001), comorbidities (Fig 1B, p=0.039), low income country (Fig 1C, p<0.001), advanced phase CML at time of COVID-19 (Fig 1D, p<0.001) had statistically significant association with overall survival (OS) in CML pts with COVID-19. OS was 71% in low or lower middle income countries, 93% in upper middle and 95% in high-income countries (Fig 1C, p<0.001). The mortality rate for pts with cardiovascular disease;heart failure, coronary artery disease, cardiomyopathies, hypertension, stroke or cerebrovascular disease (12%), and chronic lung disease (13%) were higher than those pts with other comorbidities (6%), or without comorbidities (4%;p=0.003;Fig 1E). By multivariate analysis, all these risk factors remained significantly associated with OS. For pts who were hospitalized with severe disease, age >75y (p=0.037), comorbidities (p=0.001), male gender (p=0.01), CML status (AP/BC vs CP in MMR;p=0.049), CML treatment (pre-TKI vs TFR;p=0.02) and length of time with CML (p<0.05) were significant risk factors for mortality. By multivariate analysis, all the risk factors except age remained significant. The risk factors for mortality for pts with moderate, severe, or critical disease were age >75y (p=0.003) and low and lower middle income countries (p<0.001), both confirmed by multivariate analysis. Conclusions We confirmed a higher mortality for CML pts with COVID-19 n older pts (>75y), pts with cardiovascular or pulmonary comorbidities and from low and low-middle income countries, the latter probably related to limitations in supportive care. Additionally, more deaths occurred in pts in advanced phases and in pts not in MMR.