The phase 1b multicohort KEYNOTE-013 study assessed the safety and antitumor activity of pembrolizumab given at 10 mg/kg/day every 2 weeks for up to 2 years in hematologic malignancies, including myelodysplastic syndromes (MDS) refractory to a hypomethylating agent (HMA). Primary outcomes were safety and objective response rate per International Working Group 2006 criteria. By June 26, 2020, 28 patients were enrolled; median duration of follow-up was 5.6 months (range, 1-78), and 25 patients (89%) had died. Treatment-related adverse events occurred in 10 patients (36%), including 2 (7%) treatment-related discontinuations. No patient achieved complete or partial response. Five patients (19%) had bone marrow complete response, 12 (44%) stable disease, 10 (37%) progressive disease, 6 (22%) cytogenetic response, and 5 (19%) hematologic improvement. Median overall survival (OS) was 6.0 months (95% CI, 4-12); the overall 2-year OS rate was 17%. Pembrolizumab had manageable safety and clinical activity in patients with HMA-refractory MDS.This trial was registered at www.clinicaltrials.gov as #NCT01953692.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1080/10428194.2022.2034155 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
[Explanation and interpretation of blood transfusion provisions for children with hematological diseases in the national health standard "Guideline for pediatric transfusion"].
Zhongguo Dang Dai Er Ke Za Zhi
January 2025
, Department of Pediatrics, Third Xiangya Hospital, Central South University Changsha 410013 China.
To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion is one of the most commonly used supportive treatments for children with hematological diseases. This guideline provides guidance and recommendations for blood transfusions in children with aplastic anemia, thalassemia, autoimmune hemolytic anemia, glucose-6-phosphate dehydrogenase deficiency, acute leukemia, myelodysplastic syndromes, immune thrombocytopenic purpura, and thrombotic thrombocytopenic purpura.
View Article and Find Full Text PDFRole of Population Based Studies in Advancing our Knowledge of Myelodysplastic Syndromes.
Curr Hematol Malig Rep
January 2025
Department of Medicine, University of Vermont Medical Center, Burlington, VT, USA.
Purpose Of The Review: Myelodysplastic syndromes (MDS) are myeloid neoplasms characterized by high molecular and genomic heterogeneity. Accordingly, efforts in risk assessment and therapeutic intervention mostly target unique profiles that individualize specific MDS subtypes. In this review, we explored the contributions of population based studies accounting for MDS as a group.
View Article and Find Full Text PDFA phase I study of MLN4924 and belinostat in relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome.
Cancer Chemother Pharmacol
January 2025
Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Purpose: Relapsed and/or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome continue to have a poor prognosis with limited treatment options despite advancements in rational combination and targeted therapies. Belinostat (an HDAC inhibitor) and Pevonedistat (a NEDD8 inhibitor) have each been independently studied in hematologic malignancies and have tolerable safety profiles with limited single-agent activity. Preclinical studies in AML cell lines and primary AML cells show the combination to be highly synergistic, particularly in high-risk phenotypes such as p53 mutant and FLT-3-ITD positive cells.
View Article and Find Full Text PDFThe molecular prognostic scoring system for normal karyotype myelodysplastic syndromes.
J Transl Med
January 2025
Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Background: Molecular-clinical prognostic models for Myelodysplastic syndromes (MDS) offer more accurate prognosis predictions, yet existing models often overlook the heterogeneity of mutational profiles against the cytogenetic background. Moreover, how to apply these models in regions where large panel NGS is unaffordable remains a significant challenge to be addressed.
Methods: A total of 237 NK MDS patients from our center were used as the training set to screen for key variables and develop a prognostic model with overall survival (OS) as the endpoint.
Bi-targeting of thioredoxin 1 and telomerase by thiotert promotes cell death of myelodysplastic syndromes and lymphoma.
Biol Direct
January 2025
Department of Clinical Laboratory, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang, China.
Thioredoxin1 (TRX1) and telomerase are both attractive oncology targets that are tightly implicated in tumor initiation and development. Here, we reported that the 6-dithio-2-deoxyguanosine analog thiotert exhibits an effective cytotoxic effect on myelodysplastic syndromes (MDS) cell SKM-1 and lymphoma cell U-937. Further studies confirmed that thiotert effectively disrupts cellular redox homeostasis, as evidenced by elevated intracellular reactive oxygen species (ROS) levels, increased MnSOD, accelerated DNA impairment, and activated apoptosis signal.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!