Azacitidine (AZA) for Patients with Vexas and Myelodysplastic Syndrome (MDS): Data from the French Vexas Registry

Background MDS are associated in 10% to 25% of the cases with systemic inflammatory or auto-immune diseases (SIAD). The management of SIADs in this context includes glucocorticoids and biologics with variable response rates, but we and others found that hypomethylating agents, especially azacytidine (AZA), can have some efficacy in SIADs associated with lower risk MDS (Fraison, J.-B. et al. Leuk. Res. 43, 13-17 (2016).). The recently described VEXAS syndrome (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome) (Beck et al, NEJM 2020) an autoinflammatory disease characterized by somatic mutation of the UBA1 gene, is often associated with hematological disorders, especially MDS, and its treatment is often unsuccessful Based on a French nationwide registry of patients with VEXAS syndrome, we described the efficacy and safety of AZA in VEXAS syndrome patients with concomitant MDS. Patients A French nationwide registry of 116 patients with VEXAS syndrome was established in Jan 2021. We collected in this registry patient cases with concomitant MDS (according to WHO 2016) who received at least 1 full cycle of AZA (5 to 7 days). Major response of autoinflammatory disease to AZA was defined by at least 50% steroids dose reduction to less than 10 mg/day during at least one month, and minor response by at least 50% steroid dose reduction but to > 10 mg/day, during at least one month. Results Of the 58 patients with concomitant MDS included in the French VEXAS registry, 11 had received at least 1 cycle of AZA. All patients were males and median age was 64 (range 54-73), WHO : MDS MLD (n=6) , MDS SLD (n=1), MDS EB1 (n=4) ) ,R-IPSS low (n=7), intermediate (n=3) high (n=1). Median time from MDS diagnosis to AZA onset was 8 (range 0-88) months. VEXAS phenotype mostly included skin lesions (100%), fever (91%) and constitutional symptoms (91%). All patients, except one, were steroid dependent at AZA onset. In addition to steroids, patients had received a median of 1 immunosuppressive treatment (IST) (range 0-6). The median number of AZA cycles was 11 (range 2-35). Median follow up from AZA onset was 32 months (range 12-75). Five (46%) patients discontinued AZA before the end of follow-up, after 2 to 10 cycles due to failure (n=4) and persistent response after 6 cycles (n=1). Response of autoinflammatory disease to AZA was achieved in 5 patients (45%) including major response in 2 patients, and minor response in 3, while 6 patients had no response. Best response was observed after 4 cycles (n=4) and after 6 cycles (n=1). In responders, prednisone could be discontinued in 1 patient. Duration of response was 6, 8+, 12, 21, 27+ months (Median 16.5). Three of the 5 responders subsequently received another IST. Of 10 anemic and 5 thrombocytopenic patients,3 obtained erythroid and 2 obtained platelet response, respectively (IWG 2006 criteria). Two patients experienced serious adverse events during AZA treatment, including pneumocystis pneumonia (n=1), severe colitis and bacterial pneumonia (n=1). Conclusions Our results, in a limited patient number, suggest that AZA can improve auto inflammatory symptoms in 45% of patients with VEXAS syndrome and underlying MDS, allowing decrease or even discontinuation of steroids, during a median time > 1 year, with concomitant hematological response in about 50% of the cases and limited side effects. A prospective study with more patients will be needed to confirm those results. Disclosures Comont: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Takeda: Speakers Bureau. Riviere: Octapharma: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees. Terriou: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Terrier: LFB: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astrazeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees. Georgin-Lavialle: Novartis: Membership on an entity's Board of Directors or advisory committees; Soby: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Fenaux: Syros Pharmaceuticals: Honoraria; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; JAZZ: Honoraria, Research Funding; Celgene/BMS: Honoraria, Research Funding.

Prevalence and risk factors of upper gastrointestinal cancers missed during endoscopy: a nationwide registry-based study

Background and aims A significant proportion of upper gastrointestinal cancers (UGICs) remain undetected during esophagogastroduodenoscopy (EGD). We investigated the characteristics and risk factors of UGICs missed during endoscopy. Methods In this nationwide registry-based study, we analyzed two large Polish datasets: the National Health Fund and the National Cancer Registry, to identify individuals who underwent EGD and were subsequently diagnosed with UGICs. Cancers diagnosed <6 months after EGD were defined as “prevalent” and those within ≥6 and <36 months as “missed.” We compared the characteristics of missed and prevalent cancers and analyzed the risk factors for missed UGICs in a multivariable regression model. Results We included 4,105,399 patients (mean age 56.0 [±17.4] years; 57.5% female) who underwent 5,877,674 EGDs between 2012-2018. Within this cohort, 33,241 UGICs were diagnosed, of which 1,993 (6.0%) were missed. Within esophageal neoplasms, adenocarcinomas were more commonly missed than squamous-cell cancers (6.1% vs. 4.2%) with a relative risk of 1.4 (95% confidence interval [CI]:1.2–1.5, P=0.011). In the stomach, missed adenocarcinomas constituted 5.7%. Overall, missed UGICs presented more often at an advanced stage than prevalent cancers (42.2% vs. 36.2%, P<.001). Risk factors for missed UGICs included: initial EGD performed within primary (vs. secondary) care (odds ratio[OR] 1.3, 95%CI:1.2–1.5), female gender (OR 1.3; 95%CI:1.2–1.4), and higher comorbidity (Charlson comorbidity index ≥5 vs. 0; OR 6.0; 95%CI:4.7–7.5). Conclusions Esophageal adenocarcinomas are most commonly missed among UGICs. Overlooked cancers occur more frequently within the primary care sector and are found more often in women and individuals with multiple comorbidities.

Multi-Center, Prospective, Nation-Wide Coronary Angioplasty Registry in Thailand (Thai PCI Registry): Registry Design and Rationale

Background: Coronary artery disease (CAD) is one of the most common causes of death worldwide. Percutaneous coronary intervention (PCI) is currently the main revascularization modality for these patients. The practice of PCI, outcomes and resource utilization varies in many parts of the world. Therefore, it is important to have local information regarding the patient demographics, pattern of PCI practice, and outcomes. Objective: To report the study design, protocol and rationale of the Thai PCI registry. Materials and Methods: Thai PCI Registry is a prospective, multi-center study which is an initiative project of the Cardiac Intervention Association of Thailand (CIAT). The study consisted of phase I for cross-sectional data registry and phase II for follow up study. The project was started in November 2015. All catheterization laboratories in Thailand were invited to participate in this nationwide registry. The details regarding patient characteristics, procedural details, equipment, and outcomes of PCI were prospectively collected using well-constructed case record form. The protocol of the registry has been approved by the Central Research Ethics Committee (CREC). The project received a research grant from the Health System Research Institute, The Ministry of Public Health, in Thailand, March 2017. Results: There were 39 hospitals from all areas of the country participated in the registration. The hospital type and size were varied and well represented of the PCI centers in Thailand. The registry planned to enroll all consecutive PCI patients at each hospital for approximately one year with the estimated number of PCI at 22,000 procedures. Initially, all patients were followed up for at least 6 and 12 months. Conclusion: The present study provides rationale, protocol, definition and study design of Thai PCI registry. The results of the Thai PCI registry would yield the essential information regarding the current real-world practice as well as the results and complications of PCI. Keywords: Coronary angioplasty; Nationwide registry; Percutaneous coronary intervention; Thailand; Real-world