Background: Patients with solid cancers and hematopoietic malignancy can experience systemic symptoms compatible with adult-onset Still’s disease (AOSD). The newly described VEXAS, associated with somatic UBA1 mutations, exhibits an overlap of clinical and/or biological pictures with auto inflammatory signs and myelodysplastic syndrome (MDS). Objectives: To describe a cohort of patients with signs of undifferentiated systemic autoinflammatory disorder (USAID) concordant with AOSD and MDS/chronic myelomonocytic leukemia (CMML) and the prevalence of VEXAS proposed management and outcome. Methods: A French multicenter retrospective study from the MINHEMON study group also used for other published works with the support of multidisciplinary and complementary networks of physicians and a control group of 104 MDS/CMML. Results: Twenty-six patients were included with a median age at first signs of USAID of 70.5 years with male predominance (4:1). Five patients met the criteria for confirmed AOSD. The most frequent subtypes were MDS with a blast excess (31%) and MDS with multilineage dysplasia (18%). Seven patients presented with acute myeloid leukemia and twelve died during a median follow-up of 2.5 years. Six out of 18 tested patients displayed a somatic UBA1 mutation concordant with VEXAS, including one woman. High-dose corticosteroids led to a response in 13/16 cases and targeted biological therapy alone or in association in 10/12 patients (anakinra, tocilizumab, and infliximab). Azacytidine resulted in complete or partial response in systemic symptoms for 10/12 (83%) patients including 3 VEXAS. Conclusion: Systemic form of VEXAS syndrome can mimic AOSD. The suspicion of USAID or AOSD in older males with atypia should prompt an evaluation of underlying MDS and assessment of somatic UBA1 mutation.
Autoinflammatory diseases (AIDs) are defined as disorders of innate immunity. They were initially defined in contrast to autoimmune diseases because of the lack of involvement of the adaptive immune system and circulating autoantibodies. The four monogenic AIDs first described are called the “historical” AIDs and include: Familial Mediterranean Fever (associated with MEFV mutations), cryopyrinopathies (associated with NLRP3 mutations), Tumor Necrosis Factor Receptor-associated Periodic Syndrome (associated with TNFRSF1A mutations) and Mevalonate Kinase Deficiency (associated with MVK mutations). In the last 10 years, >50 new monogenic AIDs have been discovered due to genetic advances. The most important discovery for adult patients is VEXAS syndrome associated with somatic UBA1 mutations leading to an autoinflammatory disease affecting mostly elderly men. Diagnosis of monogenic AIDs is based on personal and family history and detailed analysis of symptoms associated with febrile attacks, in the context of elevated peripheral inflammatory markers. This review proposes a practical approach of the diagnosis of the main monogenic AIDs among adult patients to guide the clinician.
as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed (PSR) BRCA-mutated OC who are in response to platinum-based chemotherapy (PBC). In addition, film-coated tablets were approved in the EU in May 2018 for PSR-OC regardless of BRCA status, and in June 2019 for adult patients with advanced BRCA-mutated OC who are in response to first-line PBC. So far, only limited data on real-world maintenance monotherapy with olaparib are available. We evaluated HRQoL during olaparib maintenance in this observational study.
Methods:The German prospective non-interventional study C-PATROL (NCT02503436) collects routine clinical and patient-reported outcome (PRO) data of BRCA-mutated PSR OC patients treated with olaparib according to label. In total, 278 patients were enrolled in the study until 30 Sep 2019 (end of recruitment). In the 4 th interim analysis (cut-off date: 22/04/20), HRQoL was evaluated during the 1 st year of olaparib maintenance therapy using the FACT-Ovarian and FACIT-Fatigue questionnaires.Results: 271 BRCAm PSR OC patients treated with olaparib were analyzed (median age: 60 yrs; ECOG 1: 93%; !2 relapses: 32%; !3 prior platinum chemotherapies: 34%). More than 80% have provided questionnaires at baseline and month 3; and >60%, 55% and 45% at month 6, 9 and 12, respectively, until data cut-off. The FACT-O total score as well as trial outcome index (TOI) remained consistent over time (mean scores
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