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Selinexor in combination with venetoclax and decitabine in patients with refractory myelodysplastic syndrome previously exposed to hypomethylating agents: three case reports.
Front Oncol
December 2024
Department of Hematology, The 923rd Hospital of the Joint Logistics Support Force of the People's Liberation Army, Nanning, China.
The management of patients with myelodysplastic syndrome (MDS) refractory to hypomethylating agents (HMAs) remains a challenge with few reliably effective treatments. Preclinical studies have shown that the inhibition of the nuclear export protein XPO1 causes nuclear accumulation of p53 and disruption of NF-κB signaling; both of which are relevant targets for MDS. Selinexor is an XPO1 inhibitor with demonstrated efficacy in MDS patients.
View Article and Find Full Text PDFVenetoclax plus D-CAG (decitabine, cytarabine, aclarubicin, G-CSF) for elderly or unfit patients with newly diagnosed acute myeloid leukemia: a multicenter, prospective study.
Ann Hematol
December 2024
Department of hematology, West China Hospital, Sichuan University, No.37 Guoxuexiang St, 610041, Chengdu, China.
Induction regimens with satisfactory remission rates are limited for patients with acute myeloid leukemia (AML) who are elderly or ineligible for intensive chemotherapy. This study is a single-arm, multicenter, prospective phase I/II study (registered with the Chinese Clinical Trial Registry as ChiCTR 2200059694 on May 8, 2022), aiming to evaluate the efficacy and safety of venetoclax plus decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor (VD-CAG) for newly diagnosed AML patients who are elderly or ineligible for intensive chemotherapy. The primary endpoint was composite complete remission (CRc) after 1 cycle of induction chemotherapy.
View Article and Find Full Text PDFDecitabine Enhances Sorafenib Sensitivity in Renal Cell Carcinoma by Promoting BIN1 and SYNE1 Expressions.
Front Biosci (Landmark Ed)
October 2024
Department of Pharmacy, Tiantai People's Hospital of Zhejiang Province (Tiantai Branch of Zhejiang Provincial People's Hospital), Hangzhou Medical College, 317200 Taizhou, Zhejiang, China.
Background: Renal cell carcinoma (RCC), especially clear cell RCC (ccRCC), significantly impacts health, and results in particularly poor outcomes in patients at the advanced stage. Resistance to vascular endothelial growth factor (VEGF) pathway-targeting tyrosine kinase inhibitors (TKIs) is a major barrier in effective ccRCC treatment. Herein, we aim to explore how decitabine mediates bridging integrator 1 (BIN1) and spectrin repeat containing nuclear envelope protein 1 (SYNE1) to impact resistance of ccRCC to sorafenib.
View Article and Find Full Text PDF[Efficacy and safety of venetoclax combined with decitabine, modified HA regimen and DLI in the treatment of relapsed pediatric AML/MDS after allogeneic hematopoietic stem cell transplantation].
Zhonghua Xue Ye Xue Za Zhi
September 2024
Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.
Article Synopsis
- The study aims to evaluate the effectiveness and safety of a treatment combining venetoclax, decitabine, cytarabine, and homoharringtonine for pediatric acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) post stem cell transplantation (HSCT).
- Data from 29 pediatric patients who relapsed or had minimal residual disease after HSCT were collected, showing an overall response rate of 75.8% and a significant improvement in complete remission rates, though serious adverse effects were common.
- The findings suggest this treatment regimen is promising for salvage therapy in pediatric AML, but highlights the need for timely transplant procedures after achieving remission to improve long-term survival rates.
Dosing of Venetoclax in Pediatric Patients with Relapsed Acute Myeloid Leukemia: Analysis of Developmental Pharmacokinetics and Exposure-Response Relationships.
Clin Ther
October 2024
AbbVie, Inc., Chicago, Illinois; Department of Clinical Pharmacy, Ain Shams University, Cairo, Egypt. Electronic address:
Purpose: This work aimed to characterize the pharmacokinetics and exposure-response relationships of venetoclax in pediatric patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) to identify venetoclax doses to be administered to pediatric patients in the phase 3 study.
Methods: Data from 121 patients across three phase 1 studies enrolling pediatric patients with R/R malignancies were utilized to develop a population pharmacokinetic model to describe venetoclax pharmacokinetics in pediatric patients. Individual patient average venetoclax plasma concentration up to the event of interest, derived based on the population pharmacokinetics analysis, was used to evaluate the exposure-response relationships to efficacy (complete response) and safety (neutropenia and thrombocytopenia) endpoints for patients with AML who received venetoclax in combination with azacitidine, decitabine, or cytarabine (n = 36).
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