Dasatinib cessation after deep molecular response exceeding 2 years and natural killer cell transition during dasatinib consolidation

作者：Kumagai Takashi^*; Nakaseko Chiaki; Nishiwaki Kaichi; Yoshida Chikashi; Ohashi Kazuteru; Takezako Naoki; Takano Hina; Kouzai Yasuji; Murase Tadashi; Matsue Kosei; Morita Satoshi; Sakamoto Junichi; Wakita Hisashi; Sakamaki Hisashi; Inokuchi Koiti

来源：Cancer Science, 2018, 109(1): 182-192.

DOI：10.1111/cas.13430

• chronic myelogenous leukemia
• dasatinib
• natural killer
• stop
• tyrosine kinase inhibitors

Tyrosine kinase inhibitors (TKI) improve the prognosis of patients with chronic myelogenous leukemia (CML) by inducing substantial deep molecular responses (DMR); some patients have successfully discontinued TKI therapy after maintaining DMR for 1year. In this cessation study, we investigated the optimal conditions for dasatinib discontinuation in patients who maintained DMR for 2years. This study included 54patients with CML who were enrolled in a D-STOP multicenter prospective trial, had achieved DMR, and had discontinued dasatinib after 2-year consolidation. Peripheral lymphocyte profiles were analyzed by flow cytometry. The estimated 12-month treatment-free survival (TFS) was 62.9% (95% confidence interval: 48.5%-74.2%). During dasatinib consolidation, the percentage of total lymphocytes and numbers of CD3(-) CD56(+) natural killer (NK) cells, CD16(+) CD56(+) NK cells and CD56(+) CD57(+) NK-large granular lymphocytes (LGL) were significantly higher in patients with molecular relapse after discontinuation but remained unchanged in patients without molecular relapse for >7months. At the end of consolidation, patients whose total lymphocytes comprised <41% CD3(-) CD56(+) NK cells, <35% CD16(+) CD56(+) NK cells, or <27% CD56(+) CD57(+) NK-LGL cells had higher TFS relative to other patients (77% vs 18%; P<.0008; 76% vs 10%; P<.0001; 84% vs 46%; P=.0059, respectively). The increase in the number of these NK cells occurred only during dasatinib consolidation. In patients with DMR, dasatinib discontinuation after 2-year consolidation can lead to high TFS. This outcome depends significantly on a smaller increase in NK cells during dasatinib consolidation.

• 出版日期2018-1