Treatment-free remission after a second TKI discontinuation attempt in patients with Chronic Myeloid Leukemia re-treated with dasatinib – interim results from the DAstop2 trial

Abstract

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. Whether these patients can achieve a second treatment-free remission (TFR) remains unclear. DAstop2 (ClinicalTrials.gov ID: NCT03573596) is a prospective study including patients with a failed first TFR attempt re-treated with any TKI for ≥ one year. Upon entering the study, patients received the TKI dasatinib for additional two years. Patients with sustained DMR for ≥1 year qualified for a second TKI stop. Ninety-four patients were included between Oct 2017-Dec 2021. At the time of data analysis, 62 patients had attempted a 2nd stop. After a median follow-up of 27 months from 2nd stop, TFR rates were 61, 56 and 46% at 6, 12 and 24 months respectively. No progression to advanced stage disease was seen and 87% had re-achieved MR4 within a median of 3 months from TKI re-initiation. In summary, we show that a 2nd TFR attempt after dasatinib treatment is safe, feasible and TFR rates seem in the range of those reported in trials of a first TKI stop.

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

“…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 ).…”

Clinical Insights into Structure, Regulation, and Targeting of ABL Kinases in Human Leukemia

“…Another TKI discontinuation trial is the DAstop2 (NCT03573596) clinical trial which is an ongoing study that aims to investigate TFR rates following a 2nd TFR attempt after DA treatment in patients who previously failed TFR with any TKI [ 112 ]. A total of 94 patients were enrolled in the trial and treated with DA 100 mg or 70 mg QD for two years.…”

“…A total of 94 patients were enrolled in the trial and treated with DA 100 mg or 70 mg QD for two years. These patients were cleared for a second TFR attempt if patients were able to re-achieve a sustained 4-log molecular response (≤0.01% BCR::ABL1 IS ) ( Table 1 ) [ 112 ]. Although the trial is ongoing, interim results as of 2024 showed that 66% of patients had attempted a second TFR attempt with TFR rates of 56% and 46% at 12 months and 24 months, respectively ( Table 1 ) [ 112 ].…”

“…These patients were cleared for a second TFR attempt if patients were able to re-achieve a sustained 4-log molecular response (≤0.01% BCR::ABL1 IS ) ( Table 1 ) [ 112 ]. Although the trial is ongoing, interim results as of 2024 showed that 66% of patients had attempted a second TFR attempt with TFR rates of 56% and 46% at 12 months and 24 months, respectively ( Table 1 ) [ 112 ]. Additionally, 87% of patients re-achieved a 4-log molecular response within 3 months of TKI re-commencement [ 112 ].…”

The Mozart effect in chronic myeloid leukaemia

“…The results are in accordance with newly published data on a second stop from the French collaborative group 10 and from the Nordic CML study group. 11 The French group investigated two additional years of nilotinib, whereas the Nordic group in an interim reported the results of a second stop attempt after at least 3 years' additional dasatinib. In the French study, treatment-free remission was sustained in 68.2% and 59.1% after 12 and 24 months, respectively, whereas the Nordic study reports that treatment-free remission was present in 61%, 56% and 46% after 6, 12 and 24 months, respectively, and 16% of the relapses occurred after 12 months.…”