Metformin use and risk of myeloproliferative neoplasms: a Danish population-based case-control study.

ABSTRACT: Previous studies have suggested that metformin has beneficial effects beyond its glucose-lowering properties, particularly in terms of its potential as an antineoplastic and cancer-preventive agent. In this study, we aimed to investigate the association between metformin use and the risk of myeloproliferative neoplasms (MPN). We conducted a population-based case-control study using Danish registers. Cases with MPN diagnosed between 2010 and 2018 were identified, and metformin use before the MPN diagnosis was ascertained. We compared metformin use among cases with MPN and an age- and sex-matched control group from the Danish general population to estimate age- and sex-adjusted odds ratios (ORs) and fully adjusted ORs (aORs) for the association between metformin use and risk of MPN. The study population included 3816 cases and 19 080 controls. Overall, 7.0% of cases and 8.2% of controls were categorized as ever-users of metformin, resulting in an OR for MPN of 0.84 (95% confidence interval [CI], 0.73-0.96) and an aOR of 0.70 (95% CI, 0.61-0.81). Long-term metformin use (≥5 years) was more infrequent and comprised 1.1% of cases and 2.0% of controls, resulting in an OR of 0.57 (95% CI, 0.42-0.79) and an aOR of 0.45 (95% CI, 0.33-0.63). A dose-response relationship was observed when cumulative duration of treatment was analyzed, and this was consistent in stratified analyses of sex, age, and MPN subtypes. In conclusion, metformin use was associated with significantly lower odds of an MPN diagnosis, indicating its potential cancer-preventive effect. Given the retrospective design, causality cannot be inferred.

Humoral and cellular immune responses after three or four doses of BNT162b2 in patients with hematological malignancies.

OBJECTIVES: Initial responses to coronavirus disease 2019 vaccination are impaired in patients with hematological malignancies. We investigated immune responses after three or four doses of BNT162b2 in patients with myeloid and lymphoid malignancies compared to controls, and identified risk factors for humoral and cellular nonresponse 1 year after first vaccination. METHODS: In 407 hematological patients (45 myeloid, 362 lymphoid) and 98 matched controls, we measured immunoglobulin G (IgG) and neutralizing antibodies specific for the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at baseline, 3 weeks, 2, 6, and 12 months, and interferon-γ release at 12 months. RESULTS: In patients with lymphoid malignancies, SARS-CoV-2 receptor-binding domain IgG concentration and mean neutralizing capacity was lower than in controls at all time points. A diagnosis of chronic lymphocytic B-cell leukemia (CLL) or lymphoma was associated with humoral nonresponse at 12 months compared to having multiple myeloma/amyloidosis (p < .001 and p = .013). Compared to controls, patients with lymphoid malignancies had increased risk of cellular nonresponse. A lymphoma diagnosis was associated with lower risk of cellular nonresponse compared to patients with multiple myeloma/amyloidosis, while patients with CLL had comparable response rates to patients with multiple myeloma/amyloidosis (p = .037 and p = .280). CONCLUSIONS: In conclusion, long-term humoral and cellular immune responses to BNT162b2 were impaired in patients with lymphoid malignancies.

The Danish Myelodysplastic Syndromes Database: Patient Characteristics and Validity of Data Records.

BACKGROUND: The Danish Myelodysplastic Syndromes Database (DMDSD) comprises nearly all patients diagnosed with myelodysplastic syndromes (MDS) in Denmark since 2010. The DMDSD has not yet been used for epidemiological research and the quality of registered variables remains to be investigated. OBJECTIVE: To describe characteristics of the patients registered in the DMDSD and to calculate predictive values and the proportion of missing values of registered data records. METHODS: We performed a nationwide cross-sectional validation study of recorded disease and treatment data on MDS patients during 2010-2019. Patient characteristics and the proportion of missing values were tabulated. A random sample of 12% was drawn to calculate predictive values with 95% confidence intervals (CIs) of 48 variables using information from medical records as a reference standard. RESULTS: Overall, 2284 patients were identified (median age: 76 years, men 62%). Of these, 10% had therapy-related MDS, and 6% had an antecedent hematological disease. Hemoglobin level was less than 6.2 mmol/L for 59% of patients. Within the first two years of treatment, 59% received transfusions, 35% received erythropoiesis-stimulating agents, and 15% were treated with a hypomethylating agent. For the majority of variables (around 80%), there were no missing data. A total of 260 medical records were available for validation. The positive predictive value of the MDS diagnosis was 92% (95% CI: 88-95). Predictive values ranged from 64% to 100% and exceeded 90% for 36 out of 48 variables. Stratification by year of diagnosis suggested that the positive predictive value of the MDS diagnosis improved from 88% before 2015 to 95% after. CONCLUSION: In this study, there was a high accuracy of recorded data and a low proportion of missing data. Thus, the DMDSD serves as a valuable data source for future epidemiological studies on MDS.