Real World Outcomes with Treatment Free Remission in Chronic Myeloid Leukemia-Experience from a Tertiary Care Cancer Centre

Abstract

Chronic myeloid leukaemia (CML) is caused by balanced translocation t(9::22)(q34;q11) resulting in formation of pathogenic BCR-ABL fusion gene. Tyrosine kinase inhibitors (TKI) have revolutionised the treatment of CML. Ongoing treatment with TKI leads to side effects and has financial impact. Teratogenic potential of TKI and growth disturbance also represent an important challenge. Thus, TKI discontinuation in form of treatment free remission (TFR) has emerged as a new and important therapeutic goal. In this retrospective study, we reviewed CML patients who were kept on TFR. Inclusion criteria was patient age ≥ 18 years diagnosed with CML in chronic phase who met the criteria for TFR and opted for same and who were in DMR but stopped TKI for any reason. We analysed the data for baseline characteristics, molecular relapse (MR), survival without molecular relapse (SWMR), TFR duration and factors affecting MR. We included 38 patients in this analysis. Thirty five (92%) patients were treated with imatinib at diagnosis. Median duration of TKI treatment was 135 months. 37 patients (97.5%) achieved DMR on TKI and median time from TKI initiation to DMR was 96 months. Median duration of DMR prior to TKI discontinuation was 41 months. TKI was discontinued after counselling for TFR in 26 patients (68%) while it was discontinued due to intolerance in 10 patients (29%). At median molecular follow up of 25 months, nine patients (23.7%) had molecular relapse. Median SWMR was not reached and 2 year estimated SWMR was 65.2% (95%CI,47.2- 83.2). Of all relapses, 5/9 (55.5%) occurred in the first six months of TFR. On univariate analysis, duration of TKI and duration of DMR were predictive of molecular relapse. On multivariate analysis, none of these factors were found to be significant. This retrospective study suggests that for CML CP patients achieving deep molecular response, discontinuing TKI therapy in real-world settings may be feasible while potentially achieving comparable outcomes.