To evaluate the long-term efficacy and safety of gilteritinib compared with salvage chemotherapy (SC) in patients with relapsed/refractory FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML). In the phase 3 COMMODORE (NCT03182244) trial, patients with relapsed/refractory FLT3-mutated AML from China, Russia, Singapore, Thailand, and Malaysia were randomized to gilteritinib (120 mg/day) or SC. The long-term follow-up included assessments every 3 months for a maximum of 3 years from the end-of-treatment visit. The primary endpoint was overall survival (OS). Secondary endpoints included event-free survival (EFS), complete remission (CR) rate, hematopoietic stem cell transplantation (HSCT) rate, and transfusion maintenance and conversion rates. Overall, 276 patients (gilteritinib, n = 137; SC, n = 139) completed the long-term follow-up. Most (88.0%) patients were Asian. The median (95% confidence interval [CI]) OS was longer with gilteritinib versus SC (10.3 [8.8, 12.7] vs 5.4 [4.1, 8.1] months, respectively; hazard ratio [HR; 95% CI], 0.612 [0.451, 0.832]), with a median follow-up of 34.6 months. The median (95% CI) EFS was longer with gilteritinib versus SC (2.1 [< 0.1, 3.2] vs 0.6 [0.2, 1.2] months, respectively; HR [95% CI], 0.589 [0.438, 0.792]). The CR rate was 20.4% and 11.5% in the gilteritinib and SC arms, respectively. During the entire study period, 22.6% and 7.9% of patients in the gilteritinib and SC arms underwent HSCT, respectively; 18.2% of patients in the gilteritinib arm received on-study HSCT. No new safety concerns were identified. Long-term gilteritinib treatment improved clinical outcomes compared with SC and was well-tolerated in a predominantly Asian population with relapsed/refractory FLT3-mutated AML.
Introduction . Abnormalities of the circle of Willis can be associated with the development of cerebrovascular pathology. Description of cases . This article presents an extremely rare clinical observation of a patient with bilateral agenesis of the internal carotid arteries who suff ered an ischemic stroke in the vertebrobasilar territory due to dissection and occlusion of one of the vertebral arteries. Discussion and conclusion . Based on the presented case and a few scientifi c publications, the possible pathogenetic link between bilateral internal carotid artery agenesis and the development of cerebrovascular disorders is discussed.
Background. Infected pseudocysts and infected walled-off necrosis (WON) are severe complications of acute pancreatitis associated with high mortality rates (up to 35%) following open surgery. The use of lumen-apposing metal stents (LAMS) enables minimally invasive endoscopic drainage; however, data on the dynamics of laboratory inflammatory markers and cavity regression during staged endoscopic debridement remain insufficient. Aims — to evaluate the efficacy and safety of transmural drainage using LAMS followed by staged endoscopic debridement and necrosectomy in patients with infected pseudocysts and infected walled-off necrosis. Methods. A prospective observational single-center study was conducted from January 2019 to March 2025. A total of 43 patients with infected pseudocysts or infected walled-off necrosis were enrolled. All patients underwent endoscopic ultrasound-guided transmural drainage with a 10-mm LAMS, followed by staged debridement for infected pseudocysts and staged necrosectomy for infected walled-off necrosis. The primary outcomes were the dynamics of C-reactive protein (CRP) levels and cavity volume. Statistical analysis was performed using the Wilcoxon signed-rank test. Results. Median CRP decreased from 132.7 (53.1; 190.2) mg/L at admission to 43.6 (14.8; 76.1) at discharge (p 0.001). Cavity volume decreased from 344.8 (88.9; 830.2) to 11.2 (5.3; 16.4) cm³ (p 0.001), representing a regression of 94.2%. A total of 30 adverse events were recorded, with hyperthermia being the most common (20 cases, 66.7% of all complications). Life-threatening complications (cyst perforation, erosive bleeding) required laparotomy in 5 patients (11.6%). Mortality was 2.3%. In patients with ineffective endoscopic treatment, the initial cavity volume exceeded 1000 mL and sequestrum size exceeded 5 cm. Conclusions. Endoscopic transmural drainage with LAMS and staged debridement effectively controls inflammation and achieves almost complete cavity regression in patients with infected pseudocysts and infected walled-off necrosis. In cases with cavity volume 1000 mL and large sequestra ( 5 cm), combined drainage techniques (percutaneous drainage, video-assisted retroperitoneal debridement) should be considered.
Abstract We report primary analysis results from the Phase 3 PERSPECTIVE study comparing ibrutinib + rituximab versus placebo + rituximab in patients with previously untreated follicular lymphoma requiring treatment per Groupe d'Etude des Lymphomes Folliculaires criteria who were ineligible for chemoimmunotherapy due to age and/or comorbidities. The primary endpoint was investigator‐assessed progression‐free survival (PFS). Patients were randomly assigned 3:1 to receive ibrutinib (560 mg) or placebo once daily until progression, together with rituximab 375 mg/m2 weekly for 4 weeks, then every 8 weeks for 12 cycles. Overall, 445 patients were assigned to receive ibrutinib + rituximab (n = 334) or placebo + rituximab (n = 111). With a median follow‐up of 53.7 months, PFS was significantly improved with ibrutinib + rituximab versus placebo + rituximab (hazard ratio, 0.713 [95% CI, 0.532–0.955]; P = 0.0231; median 42.0 vs. 32.8 months), as was overall response rate (81% vs. 68%; rate ratio, 1.190 [95% CI, 1.039–1.364]; P = 0.004). Complete response rates also favored ibrutinib + rituximab (31% vs. 26%). Overall survival (OS) was immature and not significantly different between arms (hazard ratio 1.121 [95% CI, 0.771–1.631]; P = 0.5485). Grade ≥3 adverse events occurred in 78% versus 57% of patients with ibrutinib + rituximab versus placebo + rituximab, most commonly neutropenia (16% vs. 7%), pneumonia (9% vs. 5%), hypertension (8% vs. 5%), COVID‐19 (6% vs. 2%), COVID‐19 pneumonia (6% vs. 3%), and diarrhea (6% vs. 2%). In patients with previously untreated follicular lymphoma, adding ibrutinib to rituximab significantly improved PFS and response rates but did not improve OS. This trial was registered at www.clinicaltrials.gov, NCT02947347.
