Multinational prospective study of treatment-free remission after second TKI discontinuation attempt in chronic myeloid leukemia

Tyrosine kinase inhibitor (TKI) discontinuation in chronic myeloid leukemia (CML) has become part of routine care for patients with a sustained deep molecular response (DMR). Approximately 50% experience a molecular relapse upon TKI cessation. Most of them quickly regain DMR upon TKI resumption. The prospective DAstop2 trial, at 17 centers in 7 European countries evaluated the possibility of achieving a second treatment-free remission (TFR) in patients with a failed first TFR attempt, retreated with any TKI for at least one year. Upon entering the study, patients received the TKI dasatinib for additional two years. Patients with sustained DMR for at least one year qualified for a second TKI stop. After a median follow-up of 27 months from the second stop, treatment-free remission rates were 61, 56, and 46% at 6, 12, and 24 months, respectively. No progression to advanced stage disease was observed, and 87% had re-achieved MR⁴ within a median of 3 months after TKI re-initiation. The authors conclude that a second TFR attempt after dasatinib treatment was safe and feasible, and that TFR rates were in the range of those reported in trials of a first TKI stop.