Long-term follow-up of the first Argentinian Treatment-free Remission Trial (AST) in Patients With Chronic Myeloid Leukemia

BIANCHINI M

Congreso; ESH (EUROPEAN SCHOOL OF HAEMATOLOGY); 2023

Objectives: Treatment-free remission (TFR) is now a new goal for chronic myeloid leukemia(CML) patients who achieved a long deep molecular response (DMR).The objectives of theAST trial are to estimate the TFR rate and explore prognostic biomarkers for sustained TFR.This update provides longer follow-up data and includes a new cohort of patients.Methods: AST2018 is a multicentric prospective trial conducted across fifteen centers inArgentina. Adult CML patients in chronic phase (CP) with ≥4 years of TKI treatment and ≥2years of DMR (≥RM4.0) were included, with typical BCR-ABL1 transcripts b3a2 and/or b2a2.Molecular tests were performed at 2 harmonized centralized laboratories, monthly for the first6 months, every 2 months until the 1st year and every 3 months until month 24. TKI wasrestarted if major molecular response (MMR) was lost. The immunological profile of naturalkiller (NK) cells was analyzed by flow cytometry at baseline, and at month 3 (updated inSanchez et al, sent to 25th Annual John Goldman Conference on CML).Molecular-relapse-free survival was estimated using the Kaplan-Meier method.Results: A total of 81 patients were evaluated, divided into two cohorts: 46 patients enrolledbetween February 2018 and July 2020 (first cohort, last patient last visit August 2022),and 35 patients enrolled between July 2022 and April 2023 (second cohort). Betweenthese two periods, enrollment was paused due to COVID19 pandemic.This analysis focuses on the first cohort that has completed the 24 months on trial.The median age of this cohort was 57.5 years (24-86). Twenty-four patients (52%)were female. Median treatment duration before discontinuation was 10.5 years (4.2-20). The TKI treatment previous to discontinuation was Imatinib in 34 (73%) patients,Dasatinib 8 (17%) and Nilotinib 4 (9%). According to the Sokal Risk score, 22 (47%)patients were low risk, 14 (30%) were intermediate and 10 (21%) were high. Themedian follow-up of this cohort was 40.8 months (25-47).Sixteen patients (35%) lost MMR, leading to a molecular relapse-free survival rate of65% at 24 months. All patients who lost MMR regained it after restarting the same TKItreatment, with a median time to recover response of 2.8 months (1-7). Extendedfollow-up (median 40 months) showed no late relapses or disease progressionsEleven patients (23%) were receiving non-branded TKI therapy before discontinuation,and 6 (45%) of them lost MMR. Clinical variables such as TKI treatment duration (>5.8years) and DMR duration (>40 months) were associated with an increased probabilityof maintaining response.Conclusions: The observed molecular relapse-free survival rate was slightly higherthan reported in international literature, and a longer follow-up confirmed the sustainedresponse. While the sample size was expanded, longer follow-up is needed to validatethese findings in the second cohort. The study highlights the potential for TFR as afeasible strategy in CML management in Latin America.