Preliminary results of the first TKI discontinuation study in patients with CML who achieved deep and sustained molecular remission in Argentina (Argentina Stop Trial ? AST

BIANCHINI M

Congreso; ESH; 2020

BACKGROUND: Treatment discontinuation of tyrosine kinase inhibitors (TKI) in patients with chronic myeloid leukemia (CML) is safe. Only half of patients in deep molecular response (DMR) sustain treatment-free remission (TFR). Nevertheless, a robust predictor of prolonged TFR has not been reported yet. We aim to guarantee adequate molecular monitoring (MM) for TFR in Argentina and to characterize new prognostic biomarkers to accurately identify patients able to sustain TFR.METHODS: The AST contemplates the recruitment of patients with CML (typical BCR-ABL1 transcripts b3a2 and/or b2a2) in chronic phase, treated with TKI who achieved DMR (≥MR4.0), sustained for ≥ 2 years in a standardized laboratory and with ≥ 4 years of treatment. MM is performed monthly for the first 6 months, bimonthly until the year, and every 3 months during the second year. At the time of discontinuation, at month 3, 12 and at any time when MR3.0 is lost, multiple subpopulations of Natural Killer cells (NK, CD56+CD3-) are analyzed by flow cytometry, with particular interest in tumor-induced memory like-NK cells (TIML-NK, CD57+CD16+CD158a/b+).RESULTS: We have analyzed 50 patients from 7 centers in Argentina. Four failed screening; of the remaining 46, the median age is 57 years (24-85). Twenty-two patients (48%) were in low, fourteen (30%) in intermediate and ten (22%) in high Sokal risk score. Before discontinuation thirty-five patients took Imatinib (76%), and eleven took 2G-TKI (24%). The median duration of treatment prior to discontinuation is 10.6 years (4.16-17.5). The average post-discontinuation follow-up time is 215 days (30-365). There are 11 patients (24%) who lost MR3.0 within 6 months and immediately restarted treatment. The remaining 35 still sustain MR without treatment (mean %BCR-ABL1IS=0.003%). At the time of discontinuation, the median percentage of NK cells with respect to total lymphocytes is 14.7% (5?45%) for patients and 8.6% (3-14%) for healthy donors (n=8). Patients show a two-group distribution for the presence of TIML-NK cells, a high (mean 63.3%) and a low (mean 34.1%) percentage populations are observed, with statistically significant difference (p