First- or subsequent-line second-generation tyrosine kinase inhibitors (TKIs) can be safely discontinued in patients with chronic myeloid leukemia (CML) who have deep and long-lasting molecular responses, according to a study presented at the American Society of Hematology (ASH) 58th Annual Meeting and Exposition (also published in Blood).1

Previously reported studies show that discontinuing imatinib is safe in patients with sustained deep molecular responses. For this study (STOP 2G-TKI), researchers assessed the safety of discontinuing second-generation TKIs.

Investigators enrolled 60 patients receiving first- or subsequent-line dasatinib or nilotinib who stopped therapy after at least 3 years of TKI therapy and in molecular response 4.5 (MR4.5) with undetectable BCR-ABL1 transcripts for the last 2 years before enrollment.

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With a minimum follow-up of 12 months, researchers found that 43.3% had a molecular relapse, defined as the loss of a major molecular response. Investigators observed relapses after a median time of 4 months.

The cumulative incidences of molecular relapse by 12 and 48 months were 35% (95% CI, 24.79-49.41) and 44.76% (95% CI, 33.35-59.91), respectively. At 12 and 48 months, 63.33% (95% CI, 51.14-75.53) and 53.57% (95% CI, 40.49-66.65) were still in treatment-free remission, respectively.

Patients with prior suboptimal response or TKI resistance were more likely to have a worse outcome, and a landmark analysis showed that loss of MR4.5 3 months after TKI cessation predicted failure to maintain major molecular response later on.

RELATED: TKI Cessation Appears Feasible, Safe in Patients With CML

No patients progressed toward advanced phase CML during the treatment-free phase. All patients who restarted therapy after relapse regained major molecular response and MR4.5.


  1. Rea D, Nicolini FE, Tulliez M, et al. Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. Blood. 2016 Dec 8. doi: 10.1182/blood-2016-09-742205 [Epub ahead of print]