Open Access

Background: Depression has a major impact on the disease burden of multiple sclerosis (MS). Analyses of overlapping MS and depression risk factors [smoking, vitamin D (25-OH-VD) and Epstein-Barr virus (EBV) infection] and sex, age, disease characteristics and neuroimaging features associated with depressive symptoms in early MS are scarce. Objectives: To assess an association of MS risk factors with depressive symptoms within the German NationMS cohort. Design: Cross-sectional analysis within a multicenter observational study. Methods: Baseline data of n = 781 adults with newly diagnosed clinically isolated syndrome or relapsing-remitting MS qualified for analysis. Global and region-specific magnetic resonance imaging (MRI)-volumetry parameters were available for n = 327 patients. Association of demographic factors, MS characteristics and risk factors [sex, age, smoking, disease course, presence of current relapse, expanded disability status scale (EDSS) score, fatigue (fatigue scale motor cognition), 25-OH-VD serum concentration, EBV nuclear antigen-1 IgG (EBNA1-IgG) serum levels] and depressive symptoms (Beck Depression Inventory-II, BDI-II) was tested as a primary outcome by multivariable linear regression. Non-parametric correlation and group comparison were performed for associations of MRI parameters and depressive symptoms. Results: Mean age was 34.3 years (95% confidence interval: 33.6-35.0). The female-to-male ratio was 2.3:1. At least minimal depressive symptoms (BDI-II > 8) were present in n = 256 (32.8%), 25-OH-VD deficiency (<20 ng/ml) in n = 398 (51.0%), n = 246 (31.5%) participants were smokers. Presence of current relapse [coefficient (c) = 1.48, p = 0.016], more severe fatigue (c = 0.26, p < 0.0001), lower 25-OH-VD (c = -0.03, p = 0.034) and smoking (c = 0.35, p = 0.008) were associated with higher BDI-II scores. Sex, age, disease course, EDSS, month of visit, EBNA1-IgG levels and brain volumes at baseline were not. Conclusion: Depressive symptoms need to be assessed in early MS. Patients during relapse seem especially vulnerable to depressive symptoms. Contributing factors such as fatigue, vitamin D deficiency and smoking, could specifically be targeted in future interventions and should be investigated in prospective studies.

For younger, medically fit patients with NPM1-mutated, FLT3-wildtype acute myeloid leukemia (AML) intensive chemotherapy represents standard of care (SOC), with complete remission (CR) rates observed in up to 85% of patients and 5-year overall survival (OS) rates of 40-50%. However, significant toxicity and need for hospitalization pose challenges on patients' outcome and quality of life (QoL). Venetoclax (VEN) combined with azacitidine (AZA) has demonstrated encouraging efficacy in older, unfit AML patients, achieving high CR/CRi rates and promising OS with lower toxicity. Prospective, randomized data comparing VEN/AZA to SOC in younger, fit patients are currently missing. VINCENT is a randomized-controlled, multicenter, non-inferiority, phase 2 trial (NCT05904106) evaluating VEN/AZA versus SOC in adults aged 18-70 years with newly diagnosed, NPM1-mutated, FLT3-wildtype AML. Patients medically fit for intensive chemotherapy (ECOG ≤ 2) with adequate organ function are eligible, while patients with relapsed/refractory AML or prior cytotoxic treatment are excluded. A total of 146 patients will be randomized 1:1 to receive either VEN/AZA or SOC. Hematologic remission is evaluated according to ELN 2022 guidelines. The primary endpoint is the modified event-free survival, defined as either primary induction failure, hematologic relapse, molecular failure or death. Secondary endpoints include safety, tolerability, CR/CRi/CRh/CRMRD- rates, MRD kinetics (using NPM1 RT-qPCR and MFC), relapse-free survival, OS, early mortality, health-related QoL and cumulative health-care-resource use. Patients will be followed up for at least two years post enrollment. The VINCENT trial will be the first study to provide comprehensive prospective data comparing VEN/AZA to SOC, addressing both efficacy and patient-centered outcomes.