Interim Analysis of Hematologic Malignancies (HM)-Screen-Japan 01: A Mutation Profiling Multicenter Study of Patients with AML

• Published in: Blood 2020-11, Vol.136 (Supplement 1), p.2-3
• Main Authors: Miyamoto, Kenichi, Fukushima, Kentaro, Chi, SungGi, Shibayama, Hirohiko, Hosono, Naoko, Yamauchi, Takahiro, Katagiri, Seiichiro, Gotoh, Akihiko, Morishita, Takanobu, Yanada, Masamitsu, Yamamoto, Kazuhito, Fujishima, Naohito, Takahashi, Naoto, Ogasawara, Reiki, Kondo, Takeshi, Utsu, Yoshikazu, Aotsuka, Nobuyuki, Usuki, Kensuke, ONO, Takaaki, Kobayashi, Tsutomu, Kuroda, Junya, Horiguchi, Hiroto, Iyama, Satoshi, Fukuhara, Suguru, Izutsu, Koji, Nakamura, Makoto, Kojima, Kensuke, Minami, Yosuke
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2020-139147

Background:Recently, whole exome sequencing has been performed for acute myeloid leukemia (AML) by next generation sequencing. The results revealed that certain gene mutations are identified in patients with AML. Among them,FLT3(28%),NPM1(27%),DNMT3A(26%), andIDH1/2(20%) mutations are observed in 20 to 30% of cases, while the frequencies of more than 10 other types of mutations are less than 10%. Some of these low frequency mutations are actionable mutations, which are defined as genetic DNA aberrations that are expected to elicit a response to an approved targeted therapy that is available for off-label treatment or available in clinical trials. Thus, the treatment strategies for leukemia are drastically changing with the rapid development of new drugs. Moving forward, the proper use of new agents is one of the major AML treatment issues. Especially, genome profiling analysis for newly diagnosed patients will be needed to select an optimal first line treatment. The HM-SCREEN-Japan 01 is an actionable mutation profiling multicenter study of patients with newly diagnosed AML who are unsuitable for the first standard treatment or have relapsed/refractory AML. The objective of this study is to evaluate the frequency and characteristics of cancer-related genome alterations in AML using a comprehensive genome profiling assay (FoundationOne®Heme) and determine the quality of specimens that contribute to the gene analysis. Approval was obtained from the Institutional Review Board prior to starting patient accrual at each institution. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000035233. Methods:This study was conducted by 17 participating institutions, with a sample size of 200. The eligibility criteria were as follows: 1) histological diagnosis of AML through bone marrow aspiration; 2) either of the following conditions fulfilled, i) patients with newly diagnosed AML unfit for standard treatment or ii) patients with relapsed/refractory AML; 3) sufficient sample is collected by bone marrow aspiration; 4) age at registration is 20 years or older; 5) written informed consent is taken. The primary outcome was the frequency of each genomic alteration in leukemia using FoundationOne®Heme (F1H), which is a comprehensive genomic profile that applies next-generation sequencing. The secondary outcomes evaluated the association between each cancer genome alteration and clinicopathological characteristics, prognosis, and quality of the specim