In a recent study, researchers found varying efficacy patterns with different approaches to sequencing of targeted treatments for patients with acute myeloid leukemia (AML). The results of this study were presented in a poster at the Annual Meeting of the Society of Hematologic Oncology (SOHO) by Maximilian Stahl, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and colleagues.
Patients with AML now have some targeted treatment approaches available, such as fms-like tyrosine kinase 3 (FLT3) inhibitors and isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) inhibitors. However, according to the research of Dr Stahl and colleagues, there may be differences in efficacy with different treatment sequencing approaches.
In this study, the research team examined the efficacy of targeted therapies for AML used after treatment with venetoclax, as well as the efficacy of venetoclax given after these targeted therapies. The study was a retrospective cohort study taking place at 3 academic centers in the United States. It included 53 patients who were treated with venetoclax-based therapy and then received FLT3-, IDH1-, or IDH2-inhibitor treatment, and 44 patients who received one of these targeted agents before being treated with venetoclax.
The researchers reported on response rates and overall survival (OS) data with each approach. The overall response rate (ORR) included the complete response (CR) rate, the CR with incomplete count recovery (CRi) rate, and the morphologic leukemia-free state (MLFS) rate.
Patients who were treated with venetoclax before a targeted agent had a median age of 74 years (range, 37-89). Among these patients, 31 patients had gone on to receive FLT3-inhibitor therapy, and 22 patients received IDH1/2-inhibitor therapy.
Patients being treated with FLT3-inhibitor therapy after venetoclax had an ORR of 26.7%, which included a CR rate of 10.0%, a CRi rate of 10.0%, and an MLFS rate of 6.7%. The median OS was 6.7 months (95% CI, 3.2-14.4) in this group. Patients receiving IDH1/2-inhibitor therapy after venetoclax had an ORR of 4.5%, which was all attributed to a CRi rate of 4.5%. The median OS was 3.6 months (95% CI, 1.7-14.1) for this group.
Among patients being treated with venetoclax after a targeted agent, the median patient age was 63 years (range, 29-90). In patients who received venetoclax after FLT3-inhibitor treatment, the ORR was 51.8%, which included a CR rate of 11.1%, a CRi rate of 29.6%, and an MLFS rate of 11.1%. The median OS in this group was 8.2 months (95% CI, 3.8-15.7).
Patients receiving venetoclax after IDH1/2-inhibitor therapy had an ORR of 64.7%, which included a CR rate of 29.4%, a CRi rate of 17.6%, and an MLFS rate of 17.6%. The median OS in this group was 12.8 months (95% CI, 7.2-not reached).
Dr Stahl and colleagues concluded that venetoclax maintained efficacy as a salvage therapy after targeted treatments in this study, and they reported that the FLT3 inhibitor gilteritinib showed efficacy after treatment with venetoclax. However, inhibitors of IDH1/2 appeared to have less efficacy after venetoclax treatment.
Stahl M, Shallis RM, Derkach A, et al. Outcomes based on sequential use of venetoclax based therapy and targeted therapy in acute myeloid leukemia (AML). Presented at SOHO 2022; September 28-October 1, 2022. Abstract AML-055.