Efficacy analysis of different FLT3 inhibitors in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndrome

eJHaem

article

Suresh Balasubramanian¹  Mahesh Swaminathan³  Mai M. Aly⁴  Abdul Moiz Khan¹  Bayan Al Share¹  Vikram Dhillon⁵  Enxhi Lalo⁶  Harry Ramos⁵  Katherine G. Akers⁷  Seongho Kim¹ 

[1] Department of Oncology, Karmanos Cancer Institute, Wayne State University;Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic;Department of Medicine, Roswell Park Comprehensive Cancer Center;Clinical Hematology Unit, Internal Medicine Department, Assiut University Hospital;Department of Internal Medicine, Wayne State University School of Medicine;Wayne State University School of Medicine;Shiffman Medical Library, Wayne State University;Biostatistics and Bioinformatics Core, Karmanos Cancer Institute, Wayne State University

关键词: FLT3 inhibitors;    meta-analysis;    relapsed/refractory acute myeloid leukemia;    type 1;    type 2;   

DOI  :  10.1002/jha2.616

来源: Wiley

【 摘 要 】

Several FLT3 inhibitors(i) are available to treat relapsed/refractory (R/R) FLT3-internal tandem duplicated acute myeloid leukemia (AML). This study analyzes the efficacies of various FLT3i (types 1 and 2) tested in clinical trials in treating R/R AML and high-risk myelodysplastic syndromes (HR-MDS). PubMed and EMBASE databases were searched for single/double-arm phase I/II/III R/R AML or HR-MDS clinical trials published between 1/1/2000 and 6/1/2021. The outcomes studied were composite response rate (CRc) and overall response rate (ORR). Toxicities were compared based on the organ system. The 28 studies analyzed had 1927 patients. The pooled ORR and (CRc) for all FLT3i were 53% (95% CI, 43%–63%) and 34% (95% CI, 26%–44%). Pooled ORR and CRc were 37% (95% CI, 25%–51%) and 35% (95% CI, 21%–52%) for type 1 and 58% (95% CI, 43%–71%) and 38% (95% CI, 27%–50%) for type 2, respectively. Gastrointestinal (GI) and hematological toxicity occurred in 22% (95% CI, 19%–25.4%) and 74.6% (95% CI, 70%–79%) with type 1 and 13.9% (95% CI, 12%–16%) and 57.7% (95% CI, 54.6%–60.8%) with type 2 FLT3i. QTc prolongation occurred in 2.06% (95% CI, 1.03%–3.65%) with type 1 and 7% (95% CI, 5.3%–9%) with type 2 FLT3i. Type 2 FLT3i had less GI toxicity but more QTc prolongation. Prospective studies are needed to compare the efficacy of type 1 and 2 FLT3i.

【 授权许可】

Unknown