Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2021 Dec;8(12):e902-e911.
doi: 10.1016/S2352-3026(21)00333-1.

Low-dose dasatinib in older patients with chronic myeloid leukaemia in chronic phase (DAVLEC): a single-arm, multicentre, phase 2 trial

Kazunori Murai  1 , Hiroshi Ureshino  2 , Takashi Kumagai  3 , Hideo Tanaka  4 , Kaichi Nishiwaki  5 , Satoshi Wakita  6 , Koiti Inokuchi  6 , Toshihiro Fukushima  7 , Chikashi Yoshida  8 , Nobuhiko Uoshima  9 , Toru Kiguchi  10 , Masayuki Mita  11 , Jun Aoki  12 , Satoshi Kimura  13 , Kaori Karimata  14 , Kensuke Usuki  15 , Joji Shimono  16 , Yoshiaki Chinen  17 , Junya Kuroda  17 , Yasufumi Matsuda  18 , Kensuke Nakao  19 , Takaaki Ono  20 , Katsumichi Fujimaki  21 , Hirohiko Shibayama  22 , Chisaki Mizumoto  23 , Tomoharu Takeoka  23 , Katsuhiro Io  24 , Takeshi Kondo  25 , Masatomo Miura  26 , Yousuke Minami  27 , Takayuki Ikezoe  13 , Jun Imagawa  28 , Ayako Takamori  29 , Atsushi Kawaguchi  30 , Junichi Sakamoto  31 , Shinya Kimura  32
Affiliations
Clinical Trial

Low-dose dasatinib in older patients with chronic myeloid leukaemia in chronic phase (DAVLEC): a single-arm, multicentre, phase 2 trial

Kazunori Murai et al. Lancet Haematol. 2021 Dec.

Abstract

Background: BCR-ABL1 tyrosine kinase inhibitors (TKIs) are commonly initiated in older patients with chronic myeloid leukaemia in the chronic phase at standard doses. However, because of their safety profile in this population, appropriate therapy has not been established. We aimed to investigate whether a lower than standard dose of dasatinib was an appropriate therapy for older patients with chronic myeloid leukaemia in the chronic phase.

Methods: DAsatinib, Very Low-dose, for Elderly CML-CP patients (DAVLEC) was a multicentre, single-arm, phase 2 trial done in 25 Japanese hospitals. We enrolled patients older than 70 years with newly diagnosed chronic myeloid leukaemia in the chronic phase, ECOG performance status 0-2, and no previous treatment for CML other than hydroxyurea within 4 weeks. Second-generation TKI dasatinib was given orally at a starting dose of 20% of the standard dose (20 mg/day). If the treatment was assessed as optimal response at 3 months, 6 months, and 9 months and adverse events were grade 2 or better (according to the NCI Common Toxicity Criteria v 4.0), the same dose was continued. If response was suboptimal and adverse events were grade 2 or better, the dose was increased by 20 mg/day. Once a dose reduction had been made because of a grade 3 or worse adverse event, there were no further dose increases. Treatment was discontinued if assessed as failure (disease progression to the accelerated phase or acute phase). The primary endpoint was the achievement of major molecular response at 12 months, assessed using a per-protocol analysis. This trial is registered at with the UMIN clinical trial registry, UMIN000024548, and has completed its planned observation period.

Findings: Between Nov 1, 2016, and Oct 30, 2019, 52 patients received first-line dasatinib therapy at 20 mg/day. The median age at diagnosis was 77·5 years (73·5-83·0). 35 (67%) patients were male and 17 (33%) were female. 31 (60%) of 52 patients reached major molecular response at 12 months (one-sided 95% CI 48-71), with a median follow-up of 366 days (IQR 353-372). Grade 3-4 adverse events were reported in 12 (23%) patients. Neutropenia was the most frequent grade 3-4 adverse event, occurring in three (6%) patients. No treatment-related deaths were observed.

Interpretation: Low-dose dasatinib at 20mg/day is worthy of consideration as a starting dose for older patients with newly diagnosed chronic myeloid leukaemia in the chronic phase. However, this dose needs to be further studied in a larger cohort and with a more ethnically diverse population.

Funding: Bristol-Myers Squibb.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests KM has received honoraria from Bristol-Myers Squibb, Novartis, Pfizer, Celgene, Eisai, Sanofi, Janssen, and Otsuka Pharmaceuticals. TKu received honoraria from Bristol-Myers Squibb, Novartis, Pfizer, and Otsuka Pharmaceuticals. HT received honoraria from Bristol-Myers Squibb, Novartis, Pfizer, and Otsuka Pharmaceuticals. KN received grants from Kyowa-Kirin, and honoraria from Alexion. CY received honoraria from Bristol-Myers Squibb, Novartis KK, Pfizer Japan, Otsuka Pharmaceutical, AbbVie GK, Janssen Pharmaceutical KK, Nippon Shinyaku, and Chugai Pharmaceutical. NU received honoraria from Eisai and Janssen Pharmaceutical. KU received grants from Astellas Pharma, AbbVie, Apellis, SymBio, Daiichi-Sankyo, Novartis, Janssen, Otsuka, Astellas Amgen Biopharma, Takeda, Nippon-Shinyaku, Bristol-Myers Squibb, Amgen, Alexion, Incyte, Ono, Kyowa-Kirin, Celgene, Sumitomo-Dainippon, Chugai, Pfizer, Mundi, Yakult, MSD, Gilead, and Nippon-Boehringer-Ingelheim and honoraria from Novartis, Bristol-Myers-Squibb, Sanofi, Pfizer, Abbvie, Takeda, Ono, Kyowa-Kirin, Astellas, Alexion, Eisai, MSD, Otsuka, Celgene, Daiichi-Sankyo, Nippon-Shinyaku, PharmaEssentia, Yakult, SymBio, Alexion, and Chugai. JK received grants from Bristol-Myers Squibb, Sysmex, Celgene, Ono Pharmaceutical, Otsuka Pharmaceutical, Sanofi, Kyowa Kirin, Sanofi, Chugai Pharmaceutical, Eisai, Dainippon Sumitomo Pharma, Nippon Shinyaku, Takeda, Shionogi, Asahi Kasei, Daiichi Sankyo, MSD, Taiho Pharmaceutical, and Abbvie; has received honoraria from Bristol–Myers Squibb, Janssen Pharmaceutical KK, Celgene Corporation, Ono Pharmaceutical, Takeda, Sanofi, Kyowa Kirin, Chugai Pharmaceutical, Eisai, Astellas Pharma, Nippon Shinyaku, Dainippon Sumitomo Pharma, Symbio, Daiichi Sankyo, Fujimoto Pharmaceutical, Abbvie, and Otsuka Pharmaceutical; and consulting fees from Janssen Pharmaceutical KK, Bristol-Myers Squibb, Sanofi, and Abbvie. TO received grants from Celgene, Kyowa Hakko Kirin, Chugai Pharmaceutical, TAIHO Phamaceutical; and honoraria from Celgene, Kyowa Hakko Kirin, Chugai Pharmaceutical, Novartis, Bristol-Myers Squibb, Pfizer, Otsuka Pharmaceutical, ONO Pharmaceutical, Takeda Pharmaceutical, Astellas Pharma, Eisai Pharmaceuticals, Janssen Pharm, Daiichi Sankyo, and Mundipharma. KF received honoraria from Bristol-Myers Squibb, Novartis, Pfizer, and Otsuka Pharmaceuticals. HS received honoraria from Takeda, Ono, Novartis, Janssen, Chugai, Eizai, Nippon Shinyaku, Sanofi, AstraZeneca, Bristol-Myers Squibb, Otsuka, Mundi Pharma and Kyowa Kirin; and research funding from Janssen, Ono, Celgene, Novartis, Sanofi, AstraZeneca, AbbVie, and Chugai. TKo received honoraria from Bristol-Myers Squibb, Novartis, Pfizer, Otsuka Pharmaceuticals, and Abbvie; and has served in an advisory role for Astellas Pharma and Otsuka Pharmaceutical. YMi received honoraria from Bristol-Myers Squibb, Novartis, Pfizer, and Astellas; and research funding from Ono and CMIC Holdings. ShK has received honoraria from Bristol-Myers Squibb, Novartis, Pfizer, and Otsuka Pharmaceuticals; and research funding from Bristol-Myers Squibb, Pfizer, Otsuka Pharmaceuticals, and Ohara Pharmaceuticals. All other authors declare no competing interests

Publication types

LinkOut - more resources