Dasatinib-based 2-step induction for adults with Philadelphia chromosome-positive acute lymphoblastic leukemia

Isamu Sugiura, Noriko Doki, Tomoko Hata, Ryuko Cho, Toshiro Ito, Youko Suehiro, Masatsugu Tanaka, Shinichi Kako, Mitsuhiro Matsuda, Hisayuki Yokoyama, Yuichi Ishikawa, Yasuhiro Taniguchi, Maki Hagihara, Yukiyasu Ozawa, Yasunori Ueda, Daiki Hirano, Toru Sakura, Masaaki Tsuji, Tsuyoshi Kamae, Hiroyuki FujitaNobuhiro Hiramoto, Masahiro Onoda, Shin Fujisawa, Yoshihiro Hatta, Nobuaki Dobashi, Satoshi Nishiwaki, Yoshiko Atsuta, Yukio Kobayashi, Fumihiko Hayakawa, Shigeki Ohtake, Tomoki Naoe, Yasushi Miyazaki

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

The standard treatment for adults with Philadelphia chromosome-positive (Ph1) acute lymphoblastic leukemia (ALL) in Japan is imatinib-based chemotherapy followed by allogeneic hematopoietic stem cell transplantation (HSCT). However, _40% of patients cannot undergo HSCT in their first complete remission (CR1) because of chemotherapy-related toxicities or relapse before HSCT or older age. In this study, we evaluated dasatinib-based 2-step induction with the primary end point of 3-year event-free survival (EFS). The first induction (IND1)was dasatinib plus prednisolone to achieve CR, and IND2 was dasatinib plus intensive chemotherapy to achieve minimal residual disease (MRD) negativity. For patients who achieved CR and had an appropriate donor, HSCT during a consolidation phase later than the first consolidation, which included high-dose methotrexate, was recommended. Patients with pretransplantation MRD positivity were assigned to receive prophylactic dasatinib after HSCT. All 78 eligible patients achieved CR or incomplete CR after IND1, and 52.6% achieved MRD negativity after IND2. Nonrelapse mortality (NRM) was not reported. T315Imutationwas detected in all 4 hematological relapses before HSCT. Fifty-eight patients (74.4%) underwent HSCT in CR1, and 44 (75.9%) had negative pretransplantation MRD. At a median follow-up of 4.0 years, 3-year EFS and overall survival were 66.2% (95% confidence interval [CI], 54.4-75.5) and 80.5% (95% CI, 69.7-87.7), respectively. The cumulative incidence of relapse and NRM at 3 years from enrollment were 26.1% and 7.8%, respectively. Dasatinib-based 2-step induction was demonstrated to improve 3-year EFS in Ph1 ALL. This study was registered in the UMIN Clinical Trial Registry as #UMIN000012173.

Original languageEnglish
Pages (from-to)624-636
Number of pages13
JournalBlood advances
Volume6
Issue number2
DOIs
Publication statusPublished - 2022 Jan 25

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