title: Efficacy of molecular response at 1 or 3 months after the initiation of dasatinib treatment can predict an improved response to dasatinib in imatinib-resistant or imatinib-intolerant Japanese patients with chronic myelogenous leukemia during the chronic phase.
abstract: Dasatinib is a BCR-ABL kinase inhibitor with improved potency compared with imatinib, for which efficacy and safety in imatinib-resistant and imatinib-intolerant patients with chronic myelogenous leukemia (CML) have been established. Here, an open-label phase II study evaluated the efficacy and safety of dasatinib in 50 Japanese patients with imatinib-resistant or imatinib-intolerant CML during the chronic phase (CML-CP). Dasatinib was effective in imatinib-resistant and imatinib-intolerant patients. After 12 months of dasatinib therapy, 35 patients (70%) had achieved a major molecular response (MMR) and 16 patients (32%) had achieved a complete molecular response (CMR). Among the imatinib-resistant CML-CP cohort, 21 and 8 patients had achieved an MMR and a CMR after 12 months of dasatinib therapy, respectively. Among the imatinib-intolerant CML-CP cohort, 14 and 8 patients had achieved an MMR and a CMR after 12 months of dasatinib therapy, respectively. After 18 months of dasatinib therapy, 38 out of 50 patients (76.0%) had achieved an MMR and 19 patients (38.0%) had achieved a CMR. A lower level of BCR-ABL transcript at 1 or 3 months after the initiation of dasatinib treatment was more strongly correlated with the BCR-ABL transcript level at 12 and 18 months (p ＜ 0.001) than a higher level of BCR-ABL. The T315I mutation was identified in two patients receiving dasatinib therapy. Dasatinib was generally well tolerated, with only 3 patients (5%) having treatment discontinuation as a result of adverse hematologic events (thrombocytopenia, anemia, neutropenia) and/or non-hematologic events at a 12-month follow-up evaluation. Dasatinib was a safe and effective treatment for Japanese patients with imatinib-resistant or imatinib-intolerant CML. In addition, the molecular response at 1 or 3 months predicted a response to dasatinib at 12 or 18 months.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Nippon Medical School.
authors.forename: Koiti
authors.initials: K
authors.lastname: Inokuchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumagai
authors.forename: Eri
authors.initials: E
authors.lastname: Matsuki
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Ohashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shinagawa
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hatta
authors.forename: Jin
authors.initials: J
authors.lastname: Takeuchi
authors.forename: Chikashi
authors.initials: C
authors.lastname: Yoshida
authors.forename: Hisashi
authors.initials: H
authors.lastname: Wakita
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Kozai
authors.forename: Yukari
authors.initials: Y
authors.lastname: Shirasugi
authors.forename: Shin
authors.initials: S
authors.lastname: Fujisawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Iwase
authors.forename: Shingo
authors.initials: S
authors.lastname: Yano
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Okamoto
authors.forename: Koji
authors.initials: K
authors.lastname: Oba
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sakamaki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides / Q000494:pharmacology; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm; D005260:Female; D016313:Genes, abl; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D000069439:Dasatinib