Treatment free remission in patients with chronic myeloid leukemia: recommendations of LALNET expert panel.

Abstract Tyrosine kinase inhibitors (TKI) have dramatically changed thesurvival of chronic myeloid leukemia (CML) patients and treatment-free remission (TFR) has recently merged as a new goal of CML treatment. The aim of this work was to develop recommendations for TKI discontinuation in Latin America (LA), outside clinical trials.A working group of CML experts from LA discussed 22questions regarding TFR and reached a consensus for TFR recommendations in the region.TFR is indicated in patients in first CP, with typical BCR-ABL transcripts, under TKI treatment for a minimum of 5 years, in sustained deep molecular response (DMR: MR4.5) for 2 years. Sustained DMR must be demonstrated on at least 4 IS qPCR tests, separated by at least 3 months, in the immediate prior 2 years. After 2nd line therapy, TFR is indicated in previously intolerant patients, not resistant. Molecular monitoring is recommended monthly the first 6 months, every 2-3 months from months 7 to 12, and every 3 months during the second year, indefinitely. Treatment should be reintroduced if loss of majormolecular response. Monitoring of withdrawal syndrome, glucose levels, and lipid profile are recommended after discontinuation. After TKI reintroduction, molecular monitoring is indicated every 2-3 months until MR4.0 achievement, later every 3-6 months. For TFR attempt, is mandatory to have standardized, and reliable BCR-ABL PCR tests. These recommendations will be useful for safe discontinuation in the daily practice and will benefit patients who wish to stop treatment in emergent regions, in particular, with TKI related chronic adverse events.