title: Shorter halving time of BCR-ABL1 transcripts is a novel predictor for achievement of molecular responses in newly diagnosed chronic-phase chronic myeloid leukemia treated with dasatinib: Results of the D-first study of Kanto CML study group.
abstract: To investigate the factors that affect molecular responses on dasatinib treatment in patients with chronic-phase chronic myeloid leukemia (CML-CP), we performed a clinical trial named the "D-First study." Fifty-two patients with newly diagnosed CML-CP were enrolled in this study and received 100 mg dasatinib once daily. A deep molecular response (DMR) was defined as <50 copies/μg RNA of BCR-ABL1 transcript value corrected by GAPDH, which ensures <0.01% of BCR-ABL1 transcript value according to International Scale (BCR-ABL1(IS)). The halving time for BCR-ABL1 transcripts was calculated using transcript levels before dasatinib treatment, transcript levels after 3 months of treatment, and the treatment time between these two points. In terms of molecular response, 38 of 51 (75%) patients reached major molecular response (MMR) by 12 months, and the rate of DMR by 18 months was 59% (30/51). While both BCR-ABL1 transcript levels before treatment and a shorter halving time of BCR-ABL1 transcripts (≤14 days) were significant factors affecting achievement of MMR by 12 months, the Sokal score at diagnosis was not associated with MMR. Importantly, the halving time was the only factor that predicted achievement of DMR by 18 months. We showed that patients with CML-CP treated with dasatinib can be stratified according to the early treatment response as determined by the halving time of BCR-ABL1 transcripts. These data emphasize the significance of the early response from dasatinib treatment in achieving a DMR. (ClinicalTrials.gov; NCT01464411).
authors.affiliation: Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Iriyama
authors.forename: Shin
authors.initials: S
authors.lastname: Fujisawa
authors.forename: Chikashi
authors.initials: C
authors.lastname: Yoshida
authors.forename: Hisashi
authors.initials: H
authors.lastname: Wakita
authors.forename: Shigeru
authors.initials: S
authors.lastname: Chiba
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Okamoto
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Kawakami
authors.forename: Naoki
authors.initials: N
authors.lastname: Takezako
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumagai
authors.forename: Koiti
authors.initials: K
authors.lastname: Inokuchi
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ohyashiki
authors.forename: Jun
authors.initials: J
authors.lastname: Taguchi
authors.forename: Shingo
authors.initials: S
authors.lastname: Yano
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Igarashi
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Kouzai
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sakamaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069439:Dasatinib; D018572:Disease-Free Survival; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D011446:Prospective Studies; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D012372:ROC Curve; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; C581634:BCR-ABL1 fusion protein, human; D011743:Pyrimidines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D013844:Thiazoles; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib