The immunological mechanism of treatment-free remission is not clearly understood. We aimed to identify immune-related genetic differences that predict molecular relapse after tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic phase chronic myeloid leukemia (CML). In this prospective multicenter study, patients who were treated with TKI for at least 3 years discontinued TKI and were monitored for loss of major molecular response. We used NanoString profiling to find gene expression differences associated with relapse. From August 2019 to April 2020, 42 patients were enrolled from five centers in South Korea. During the median follow-up of 16.9 months, 47.6% (20/42) of patients experienced molecular relapse. The 6- and 12-month molecular relapse-free survival (RFS) rates were 52.5% and 50%, respectively. The e14a2 transcript type and longer duration (≥ 50 months) of deep molecular response before TKI discontinuation were associated with longer molecular RFS. NanoString analysis revealed significant differences in immune-related gene expression between relapsed and non-relapsed patients at the time of TKI discontinuation, including T cell-related genes such as SIGLEC1, ARG2, CD160, and IFNG. In conclusion, differences in expression of immune-related genes may provide a prognostic marker for relapse after TKI discontinuation in patients with CML.
Park et al. (Thu,) studied this question.