演題抄録

臓器別シンポジウム

開催概要
開催回
第58回・2020年・京都
 

慢性骨髄性白血病、チロシンキナーゼ阻害剤の到達点と限界、そして「これから」

演題番号 : SY23-2

[筆頭演者]
木村 晋也:1 

1:佐賀大学・血液・呼吸器・腫瘍内科

 

ABL tyrosine kinase inhibitors (TKIs) have improved the prognosis of chronic myeloid leukemia (CML). The current goal of CML treatment is not prolongation of survival with TKIs but treatment free remission (TFR). We performed three multi-center phase II trials including stop first-line imatinib after confirming stable deep molecular response (DMR) for at least 2 year (DOMEST), stop second- or subsequent-line dasatinib (DADI) and first-line dasatinib (1st-DADI) after at least 1 year DMR. TFR rates at 12 months in DOMEST (IJCO 2019), DADI (Lancet Haematol 2015) and 1st-DADI (Lancet Haematol 2020) were 68.6%, 48.0% and 55.9%, respectively. Assuming that 100% of eligible patients stop TKIs, this will reduce medical expense by approximately 7 billion yen over three years in Japan (Cancer Sci 2020).
In DADI trial, higher NK cell and lower regulatory T cell counts before discontinuation dasatinib correlated with successful TFR (Lancet Haematol 2015). We reported allelic polymorphisms of KIRs and HLAs were associated with favorable prognostic factor for achieving DMR in patients with CML in chronic-phase (Cancer Immunol Res 2018). Whereas KIR polymorphisms did not affect TFR and patients with HLA-A*02, *11 or *24 were independent favorable prognostic factors for TFR. Taken together, NK cells immunity might contribute to the achievement of DMR, while T-cell immunity might contribute for sustained TFR (in revision).
Since therapeutic options for CML patients who are resistant for TKIs are limited. Furthermore, CML leukemic stem cells (LSCs) are highly resistant to TKIs and cause relapse after TKI discontinuation. We developed an orally available hypomethylating agent, OR-2100, which was effective for adult T cell leukemia cells (Blood 2020). Aberrant DNA methylation plays an important role in TKIs-resistant cells and LSCs. Therefore, we are examining the effects of OR-2100 on CML LSCs.

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