RESUMO
In recent years, the association of venetoclax (VEN) with hypomethylating agents (HMAs) significantly improved the outcome of patients with newly diagnosed acute myeloid leukemia (AML) who were unfit for intensive chemotherapy and became the standard of care after the publication of the pivotal RCT VIALE-A. However, it is still not clear to what extent the results observed in the VIALE-A apply to a real-world setting. For this reason, we carried out a systematic review and meta-analysis of real-world studies on newly diagnosed patients with AML, ineligible for intensive induction chemotherapy, receiving first-line VEN+HMA. We then compared their results in term of survival with those from the VIALE-A. Kaplan-Meier curves were extracted from all included studies and individual survival data was reconstructed. We then estimated a pooled survival curve and compared it with the results of the VIALE-A using the log-rank test. We also conducted a secondary analysis including only studies considering VEN plus azacytidine (AZA) as treatment, as this was the schedule originally used in the VIALE-A. Nineteen real-world studies met the inclusion criteria and were included in the systematic review. Most of them reported a worse survival than the VIALE-A. The pooled survival curve was similar to that reported in the VIALE-A during the first three months of treatment but diverged thereafter (p-value = 0.0001). The pooled median survival among the real-world studies was 9.37 months (95%CI 8.81-10.5), substantially lower than that reported in the VIALE-A (14.7 months; 95%CI 11.9-18.7). Results slightly increased when the analysis was restricted to the studies using VEN+AZA as treatment (median survival: 11.5 months; 95%CI 10.2-14.8). Survival of newly diagnosed AML patients treated with VEN+HMAs in a real-world setting seems to be lower than previously reported in the VIALE-A, while the effect of VEN+AZA is more in line with expected results. Future studies are needed to evaluate whether this apparent discrepancy is due to the different characteristics of enrolled patients or to a non-optimal adherence to therapy, and whether alternative regimens can provide better results in terms of safety and effectiveness.
RESUMO
OBJECTIVE: To find a definition of chronic disease based on literature review and to estimate the population-based prevalence rate of chronicity in a province in Northern Italy. DESIGN: Retrospective observational study based on administrative databases. DATA SOURCES/SETTING: Archives of the National Health Service that contain demographic and administrative information linked with the archives of ticket exemptions (2000-2019), the hospital discharge and drug prescriptions (2016-2019). PARTICIPANTS: Subjects who lived in Vercelli Local Health Authority, a Northern Italian province (Piedmont region), and were alive in December 2019. MAIN OUTCOME MEASURES: Prevalence of subjects with at least one chronic disease identified by administrative sources and stratification of population according to the number of comorbidities. The pathologies considered were: chronic ischaemic heart disease, congestive heart failure, cardiac arrhythmias, hypertension, stroke, neoplasm, asthma, chronic obstructive pulmonary disease, diabetes, thyroid disorders, osteoporosis, rheumatoid arthritis, chronic kidney disease, dementia, autism spectrum disorder, depression, schizophrenia, hepatitis, HIV and substance use disorders. RESULTS: Our target population was about 164 344 subjects. The overall prevalence of subjects with at least one chronic condition was 21.43% (n=35 212): 19 541 were female and 15 671 were male with a raw prevalence of 22.96% and 19.77%, respectively. The overall prevalence increases with age until 85 years old, then a decrease is observed. Moreover, 16.39% had only one pathology, 4.30% two diseases and 0.74% had a more complex clinical condition (more than three diseases). CONCLUSIONS: Despite the difficulty of having a unique definition of chronic disease, the prevalence obtained was coherent with the estimates reported by other national surveillance systems such as Passi and Passi d'Argento. Underestimates were observed when international comparisons were done; however, when we used less stringent definitions of chronic diseases, similar results were obtained.