Dasatinib cessation after deep molecular response exceeding 2 years, and NK cell transition during dasatinib consolidation

Abstract

Tyrosine kinase inhibitors (TKIs) improve the prognosis of patients with chronic myelogenous leukemia (CML) by inducing substantial deep molecular responses (DMRs); some patients could successfully discontinue TKI therapy after maintaining DMR for ≥1 year. In this cessation study, we investigated the optimal conditions for dasatinib discontinuation in patients who maintained DMR for ≥2 years.

This study included 54 patients with CML who were enrolled in 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 >7 months. 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 < 0·0008; 76% vs. 10%; p < 0·0001; 84% vs. 46%; p = 0·0059, respectively). The increase in the number of these NK cells occurred only during dasatinib consolidation but disappeared after discontinuation.

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.

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