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. 2024 Apr;38(4):781-787.
doi: 10.1038/s41375-024-02145-6. Epub 2024 Jan 26.

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

Hjalmar Flygt  1 , Stina Söderlund  2 , Johan Richter  3 , Susanne Saussele  4 , Perttu Koskenvesa  5 , Leif Stenke  6 , Satu Mustjoki  5   7   8 , Andreja Dimitrijevic  9 , Jesper Stentoft  10 , Waleed Majeed  11 , Lydia Roy  12 , Dominik Wolf  13   14 , Arta Dreimane  15 , Bjørn Tore Gjertsen  16 , Tobias Gedde-Dahl  17 , Erik Ahlstrand  18 , Berit Markevärn  19 , Henrik Hjorth-Hansen  20 , Jeroen Janssen #  21 , Ulla Olsson-Strömberg #  2
Affiliations

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

Hjalmar Flygt et al. Leukemia. 2024 Apr.

Erratum in

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.

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Conflict of interest statement

Study drug was provided by BMS. DW have received study support and honoraria from BMS, Novartis, Pfizer, Austrian Orphan Pharma and Incyte. SS have received honoraria from BMS, Novartis, Incyte, Roche and research support from Incyte and Novartis. In addition, the Nordic CML Study group have other projects supported by Incyte, Pfizer and Austrian Orphan Pharma.

Figures

Fig. 1
Fig. 1. Study outline.
Patients with a previous failed discontinuation attempt within EURO-SKI or according to EURO-SKI criteria were eligible for inclusion. After inclusion, patients were switched to dasatinib for a minimum of two years. Patients with ≥3 years of TKI treatment and stable MR4 or better for ≥1 year were eligible for a second discontinuation attempt.
Fig. 2
Fig. 2. Consort diagram of study progress.
Out of 94 included patients, 64 patients had reached 24 months, and 62 were eligible for TKI discontinuation.
Fig. 3
Fig. 3. Treatment-free remission (TFR) after second tyrosine kinase inhibitor (TKI) discontinuation.
TFR probability at 6, 12 and 24 months was 61, 56 and 46% respectively.
Fig. 4
Fig. 4. Treatment-free remission (TFR) after second tyrosine kinase inhibitor (TKI) discontinuation by first TFR duration.
Patients with a second discontinuation divided by whether the time to molecular relapse after the first discontinuation attempt was more or less than 6 months. The log rank test was used when comparing groups.
See this image and copyright information in PMC

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