PRELIMINARY RESULTS OF THE FIRST TKI DISCONTINUATION STUDY IN PATIENTS WITH CML WHO ACHIEVED DEEP AND SUSTAINED MOLECULAR REMISSION IN ARGENTINA (STOP TRIAL ? AST)?

MOIRAGHI, B; CUSTIDIANO, R; MARIANO, R; GIERE, I; MELA OSORIO, MJ; FONCUBERTA, C; SANCHEZ AVALOS, JC; SANCHEZ, MB; VENTRIGLIA, V; BENDEK, GE; VERA, M; RUIZ, MS; PAVLOVSKY, M; FERNANDEZ, I; BIANCHINI, M; VARELA, A; FREITAS, J; GARCÍA DE LA BANCA, A; LEVY, E; VASCONCELOS CORDOBA, B; JUNI, M; MORDOH, J; PAVLOVSKY, C

Congreso; 25th Congress of the European Hematology Association (virtual edition).; 2020

European Hematology Association

Background: Treatment discontinuation of tyrosine kinase inhibitors (TKI) in patients with chronic myeloid leukemia (CML) is safe. About half of patients in deep molecular response (DMR) sustain treatment-free remission (TFR) while those who don?t regain molecular response after treatment reintroduction. In order to attempt TFR, intensive molecular monitoring (MM) by RT-qPCR in a standardized laboratory is mandatory. A robust predictor of prolonged TFR has not been reported yet. Aims: First, to guarantee adequate MM for TFR in Argentina; second, to characterize new prognostic biomarkers helpful to identify more accurately the patients who will be able to sustain the 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 carried out in 2 harmonized laboratories, monthly for the first 6 months, every 2 months until the year, and every 3 months during the second year. If patients lose MR3.0 they restart treatment immediately. In addition, at the time of discontinuation, at month 3, 12 and at any time when MR3.0 is lost, the immunological profile of multiple subpopulations of Natural Killer cells (NK, CD56+CD3-) is analyzed by flow cytometry, with particular interest in subpopulation CD57+CD16+CD158a/b+ defined as tumor-induced memory like-NK cells (TIML-NK). Results: To date we have analyzed 50 patients from 7 centers in Argentina(3 public and 4 private). Informed consent was obtained in all cases. Four patients failed screening; of the remaining 46, the median age is 58 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%). Thirty-nine percent (18/46) of the patients achieved MR3.0 before twelve months under TKI treatment. The median duration of treatment prior to discontinuation is 10.6 years (4.16-17.5). The average post-discontinuation follow-up time is 128 days (1-300). There are 6 patients (13%) who lost MR3.0; one at month 2, three at month 3 and two atmonth 5, all of them immediately restarted the treatment. The remaining 40 still sustain MR without treatment (mean %BCR-ABL1IS = 0.008%). 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), suggesting a positive effect of the TKIs on that population. 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 < 0.01). Interestingly, the mean value (60.9%) of TIML-NK cells of all patients (n = 6) who lost MR3.0 belongs to the high group.Summary/Conclusion: This is the first multicenter study of TKI discontinuation in real life in Argentina, which is currently in the enrollment phase of patients. Due to the short follow-up, results do not allow conclusions yet; however, the study of the immune system shows a phenotypic heterogeneity that may correlate with the clinical outcome of patients. This discontinuation study will allow significant saving of economic resources and may improve the quality of life of patients who currently suffer adverse effects of treatment.