Abstract
The use of small molecule inhibitors in acute myeloid leukaemia (AML) has become ubiquitous with the US Food and Drug Administration approval of multiple agents between 2017 and 2018. Despite the promise, some of these indications are based on early efficacy data (phase I/II), and single-arm studies, and have not been tested in randomised trials. Furthermore, there are important limitations in the evidence that exists in randomised trials. This perspective aims to summarise the data that formed the basis for approval of gilteritinib, glasdegib, ivosidenib, enasidenib and venetoclax. It also aims to shed a light on some of the limitations in the evidence. Clinicians should exercise caution when using drugs that largely have yet to show an improvement in survival over the standard of care in AML.
Highlights
The use of small molecule inhibitors in acute myeloid leukaemia (AML) has become ubiquitous with the US Food and Drug Administration approval of multiple agents between 2017 and 2018
The clinical benefit of these therapies is modest, but their uptake has been on the rise, with national guidelines, such as the National Comprehensive Cancer Network (NCCN), recommending them for indications that fall outside their tested purpose [1]
The cornerstone of treatment for patients with AML for the last 50 years has been intensive chemotherapy consisting of anthracycline plus cytarabine [2], which is associated with 70%–80% complete remission (CR) rate, and long-term survival, with consolidation high dose cytarabine or stem cell transplantation in high-risk patients, of about 50% [3]
Summary
The use of small molecule inhibitors in acute myeloid leukaemia (AML) has become ubiquitous with the US Food and Drug Administration approval of multiple agents between 2017 and 2018. Hypomethylating agents (HMAs) (e.g., decitabine and azacitadine) were introduced in the treatment landscape and have been shown to improve outcomes of older patients with AML, and are considered standard of care treatments for patients ineligible for intensive chemotherapy [6]. A first-in-class human phase Ib/II trial in patients with IDH1-mutated relapsed or refractory AML showed a CR/CRh rate of 30%, DOR of 8.2 months (95% CI 5.5–12), and median OS of 8.8 months (95% CI 6.7–10.2) [12].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
