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

Abstract

Abstract 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.

Keywords

• FLT3 inhibitors
• meta‐analysis
• relapsed/refractory acute myeloid leukemia
• type 1
• type 2