Final report of TKI discontinuation trial with dasatinib for the second attempt of treatment‐free remission after failing the first attempt with imatinib: Treatment‐free Remission Accomplished by Dasatinib (TRAD) study

Abstract

SummaryMultiple studies have reported a significant treatment‐free remission (TFR) rate of 50%–60% in patients with chronic myeloid leukaemia (CML) who discontinue tyrosine kinase inhibitor (TKI) therapy. However, the remaining half of these patients still require re‐initiation of TKI therapy for leukaemia control. It remains unclear if TKI drugs should be switched for re‐therapy in patients who failed the first TFR (TFR1) attempt. Our study attempted to determine whether dasatinib therapy after TFR1 failure post‐imatinib discontinuation could improve the likelihood of TFR2. Of 59 patients who lost molecular response after imatinib discontinuation for TFR1, 55 patients (93.2%) were treated with dasatinib, of whom 49 (89.1%) regained MR4.5 or deeper response, with a median time of 1.85 months to achieve MR4.5. Dasatinib was discontinued in 35 patients for TFR2 attempt, of whom 26 patients (74.28%) lost MMR and 6 (17.14%) MR4. Risk factor analysis for the TFR2 after dasatinib discontinuation suggested three significant factors: (1) doubling time of BCR::ABL1 transcript following TFR1 attempt, (2) rapid regaining of molecular response following dasatinib therapy and (3) undetectable BCR::ABL1 transcript prior to TFR2 attempt. The present study showed that dasatinib does not increase the TFR2 rate in general, but a selected group of patients could benefit from this approach.

Kinetics of BCR::ABL1 transcript levels and molecular relapse after tyrosine kinase inhibitors discontinuation in chronic myeloid leukemia patients: preliminary results from the DES-CML study

“…The French group was the first to demonstrate the feasibility of a second TKI discontinuation attempt, with a TFR rate of 36% at 24 months ( 30 ). In the TRAD study, 59 patients who failed in the first TFR attempt were treated with dasatinib, and 35 achieved MR4.5 or more profound molecular responses and were able to try a second attempt, but 74% lost MMR ( 31 ). In the DAstop2 trial, for patients eligible for a second discontinuation attempt, the TFR rate after stopping dasatinib was 46% at 24 months ( 32 ).…”