Open AccessSilent NK/T cell reactions to dasatinib during sustained deep molecular response before cessation are associated with longer treatment‐free remission
Author(s) -
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
Publication year - 2020
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14518
Subject(s) - cd8 , gastroenterology , medicine , natural killer cell , dasatinib , discontinuation , cd3 , immunology , cytotoxic t cell , tyrosine kinase , biology , antigen , receptor , biochemistry , in vitro
This study presents the final report of the multicenter, prospective tyrosine kinase inhibitor discontinuation study, D‐STOP, after a 3‐year follow‐up of 54 patients with chronic CML who discontinued dasatinib after a sustained deep molecular response (DMR) for ≥2 years with dasatinib treatment. Estimated treatment‐free remission (TFR) rates at 12 and 36 months were 63.0% [95% confidence interval (CI): 48.7‐74.3] and 59.3% (95% CI: 45.0‐71.0), respectively. CD3 − CD56 + NK, CD16 + CD56 + NK, and CD57 + CD56 + NK large granular lymphocyte (NK‐LGL), CD8 + CD4 – cytotoxic T cell, and CD57 + CD3 + T‐LGL cell numbers were relatively elevated throughout the 24‐month consolidation only in failed patients who molecularly relapsed within 12 months. In successful patients, these subsets elevated transiently after 12 months, but returned to basal levels after 24‐month consolidation. Therefore, smaller changes in NK/T, particularly the NK subset throughout consolidation, reflected higher TFR rates. TFR rates of those patients exhibiting elevation in CD3 − CD56 + NK >376 cells/μL, CD16 + CD56 + NK > 241 cells/μL, or CD57 + CD56 + NK‐LGL >242 cells/μL during consolidation compared with others were 26.7% (8.3%‐49.6%) vs 78.3% (55.4%‐90.3%), HR 0.032 (0.0027‐0.38; P = .0064), 31.2% (11.4%‐53.6%) vs 85.0% (60.4%‐94.9%), HR 0.039 (0.0031‐0.48; P = .011), or 36.8% (16.5%‐57.5%) vs 77.3% (53.7%‐89.8%), HR 0.21 (0.065‐0.69; P = .010), respectively. Therefore, silent responses of T/NK subsets to dasatinib throughout consolidation were significant for longer TFR. Elevated NK/T, particularly NK lymphocytes responsive to dasatinib, may be immunologically insufficient to maintain TFR. Their decline, subsequently replaced by altered lymphocyte population with less response to dasatinib during sustained DMR, might be immunologically significant. (D‐STOP, NCT01627132).