Effect of transcript type and droplet digital polymerase chain reaction on successful treatment-free remission in chronic myeloid leukemia patients who discontinued tyrosine kinase inhibitor.

BACKGROUND

Droplet digital polymerase chain reaction (ddPCR) is an exact method of measurement.

OBJECTIVES

We conducted this study to identify the prognostic factors for successful treatment-free remission in patients with chronic-phase chronic myeloid leukemia who discontinued tyrosine kinase inhibitors (TKIs). We also aimed to validate ddPCR for predicting molecular relapse.

DESIGN

This is a prospective, multicenter study.

METHODS

We enrolled patients treated with TKIs for at least 3 years with a confirmed sustained deep molecular response (DMR) for at least 1 year. TKI was re-administered in patients who experienced the loss of major molecular response (MMR).

RESULTS

A total of 66 patients from five institutions in South Korea were enrolled. During a median follow-up period of 16.5 months, 29/66 (43.9%) patients experienced molecular relapse; the probability of molecular relapse-free survival (RFS) at 6 or 12 months after TKI discontinuation was 65.6% or 57.8%, respectively, with most molecular relapses occurring within the first 7 months. All patients who lost MMR were re-treated with TKI, and all re-achieved MMR at a median of 2.8 months. E14a2 transcript type ( = 0.005) and longer DMR duration (⩾48 months) prior to TKI discontinuation ( = 0.002) were associated with prolonged molecular RFS and with sustained DMR. Patients with both e13a2 transcript type and detectable (⩾MR) by ddPCR at the time of TKI discontinuation showed shorter duration of molecular RFS ( = 0.015).

CONCLUSION

Our data suggest that transcript type and transcript levels on ddPCR should be taken into consideration when deciding whether to discontinue TKI therapy.