P691: Modelling of Immune Response in Chronic Myeloid Leukemia Patients Suggests Potential for Treatment Reduction Prior to Cessation

Abstract

Background: Background:Chronic myeloid leukemia (CML) is a malignancy driven by the characteristic BCR-ABL1-fusion oncogene, while the BCR-ABL1 transcript is used as a marker for diagnosis and monitoring. The introduction of tyrosine kinase inhibitors (TKI) marked a substantial progress in CML therapy. Current efforts focus on the discontinuation of TKI therapy for well-responding patients as the long-term drug administration is associated with side effects and high economical costs. Many studies reported that about 50% of patients can achieve sustained treatment free remission (TFR) while 50% present with molecular disease recurrence, typically within two years of stopping. It has been speculated that the immune system (IS) plays a major role in the control of residual disease levels and influences the individual recurrence behaviour. The recently published DESTINY trial (Clark et al., Lancet Haematol, 2019; NCT 01804985) showed that TKI dose reduction prior to cessation can proactively increase the fraction of patients to remain in sustained TFR. However, there has been no systematic investigation to evaluate how dose reduction regimens can further improve the success of TKI stop trials.