ABSTRACT
The authors would like to retract the entire article above based on a genuine error noticed after publication. More precisely, as part of further analysis with the data set, they discovered the depression variables were inadvertently mislabeled (e.g., lifetime depression was labeled as 12-months depression). Consequently, the results and conclusions of the article are significantly affected.Copyright © The Author(s), 2023.
ABSTRACT
Background: PTEFb/CDK9-mediated transcription of short-lived anti-apoptotic survival proteins and oncogenes like MCL-1 and MYC plays a critical role in a variety of cancers. VIP152 (formerly BAY 1251152), a potent and highly selective CDK9 inhibitor, has been evaluated in a Phase 1 dose-escalation study in patients with advanced cancer. The maximum tolerated dose was 30 mg once weekly administered in consecutive 21-day cycles, based on neutropenia as the dose-limiting toxicity (JCO 2018;36:2507;NCT02635672). DHL is defined as dual rearrangement of the MYC gene and either the BCL2 or BCL6 genes;the resulting overexpression of MYC and BCL2/BCL6 make it particularly difficult to treat. Patients with DHL have a poor prognosis and no standard of care. Considering the impact of CDK9 inhibition on MYC, an exploratory cohort of patients with DHL was added to the study. Methods: Patients with refractory or relapsed DHL were eligible. VIP152 was administered once weekly as a 30-minute IV infusion on Days 1, 8 and 15 of a 21-day cycle. Tumor response was assessed according to the revised Cheson criteria (2007). Results: To date a total of 7 patients have been enrolled and were evaluable at the time of data cutoff (24NOV2020). The patients were mostly men (6/7 pts, 86%) with a median (range) age of 70 (58-84) years. All patients received ≥2 prior therapies, including 2 patients with bone marrow transplant. Three of 7 patients (29%) had ≥3 prior therapies. The median time on treatment was 22 days (range 8-1361 days). The most common adverse events of any grade were: constipation, fatigue, nausea (each 3/7 pts, 43%) and abdominal pain, diarrhea, lymphocyte count decrease, neutrophil count decrease, skin infection, tumor pain, and vomiting (each 2/7 pts, 29%). Most were Grade 1 and Grade 2. The Grade 3 adverse events were fatigue, lymphocyte count decrease, neutrophil count decrease (each 1/7 pts, 14%) and tumor pain (2/7 pts, 29%). One Grade 4 lymphocyte count decrease was reported. Two patients had a serious adverse event (Grade 3 syncope and Grade 3 tumor pain). Two patients had dosing held for an adverse event;however, no patient withdrew from treatment due to any adverse events. One death occurred due to disease progression. Pharmacodynamic biomarker analysis showed significant reduction of MYC, PCNA, and MCL-1 mRNA in all patients across multiple timepoints. Antitumor activity consisted of 2 complete metabolic responses in 7 patients (29%) based on investigator-assessed FDG-PET scans. Due to the COVID pandemic, the patients withdrew consent after 3.7 and 2.3 years, respectively, of treatment. Both patients were in complete metabolic response. Conclusions: VIP152 had a manageable safety profile, on-target pharmacodynamic activity and signs of durable monotherapy antitumor activity in patients with DHL. These encouraging results warrant further evaluation of VIP152 in patients with MYCdriven lymphoma and solid tumors.
ABSTRACT
AIMS: To assess whether there is a change in the prevalence of depression and suicidal ideation after the strict lockdown measures due to the first wave of the COVID-19 pandemic in Spain; and to assess which are the factors associated with the incidence of a depressive episode or suicidal ideation during the lockdown. METHODS: Data from a longitudinal adult population-based cohort from the provinces of Madrid and Barcelona were analysed (n = 1103). Structured face-to-face home-based interviews (pre-pandemic) and telephone interviews were performed. Both depression and suicidal ideation were assessed through an adaptation of the Composite International Diagnostic Interview (CIDI 3.0). A variety of validated instruments and sociodemographic variables including age, sex, educational level, occupational status, home quietness, screen time, resilience, loneliness, social support, physical activity, disability, economic situation and COVID-19-related information were also considered. Population prevalence estimates and multivariable logistic regressions were computed. RESULTS: Overall, prevalence rates of depression and suicidal ideation did not change significantly from before to after the COVID-19 outbreak. However, the rates of depression among individuals aged 50+ years showed a significant decrease compared to before the pandemic (from 8.48 to 6.41%; p = 0.01). Younger individuals (odds ratio (OR) = 0.97 per year older; 95% confidence interval (CI) = 0.95-0.99) and those feeling loneliness (OR = 1.96; 95% CI = 1.42-2.70) during the lockdown were at an increased risk of developing depression during the confinement. Resilience showed a protective effect against the risk of depression (OR = 0.46; 95% CI = 0.32-0.66) and suicidal ideation (OR = 0.33; 95% CI = 0.16-0.68), whereas individuals perceiving social support were at a lower risk of developing suicidal thoughts (OR = 0.35; 95% CI = 0.18-0.69). CONCLUSIONS: Continuous reinforcement of mental health preventive and intervening measures during and in the aftermath of the crisis is of global importance, particularly among vulnerable groups who are experiencing the most distress. Future research should strive to evaluate the long-term effects of the COVID-19 crisis on mental health.