CML-266: Second Generation Tyrosine Kinase Inhibitors in First Line Can Reduce the Time to Treatment-Free Remission in Chronic Myeloid Leukemia Patients

Introduction Duration of treatment with tyrosine kinase inhibitors (TKI) is an important favorable prognostic factor for treatment-free remission (TFR) and deep molecular response (DMR) in patients (pts) with chronic myeloid leukemia (CML). Aim To analyze the impact of first-line treatment duration with imatinib and 2G TKI on molecular relapse-free survival (MRFS) in CML pts with sustained DMR. Patients and methods In total, 174 CML pts in chronic phase with ≥3 years treatment duration and sustained DMR (MR4-MR5, BCR-ABL IS 0.1%). Median (Me) age of pts was 43 (range 21-86) years; 39% were males. Me TKI treatment duration was 86 months (IQR 57-125 mo), Me DMR duration was 45 (IQR 29-66 mo). Imatinib, 2G TKI in first-line and 2G TKI in second-line were discontinued in 116 (66.7%), 15(8.6%) (11 nilotinib, 3 dasatinib, 1 bosutinib) and 43 (24.7%) (34 nilotinib, 9 dasatinib) pts respectively. Results Me follow-up time after treatment cessation was 33 months (range 1-133). MRFS at 6, 12, 24 and 36 months was 62% (CI: 55-70%), 53% (CI: 45-60%), 50% (CI: 42-57%) and 48% (CI: 40-56%) respectively. Treatment duration and MR4.5 vs MR4 were significant for MRFS both in univariate (p=0.009 and p=0.015) and multivariate analysis (p=0.017 and p=0.037). No difference in 36 months MRFS was observed for imatinib (47% (CI: 42-60%)), first-line 2G TKI (59% (CI: 33-84%) p=0.58) and second-line 2G TKI (47% (CI: 32-63%) p=0.97) groups. However, significantly shorter treatment duration was observed in first-line 2G TKI group (Me=44 mo (IQR 40-52 mo)) vs imatinib (Me=93 mo (IQR 69-127 mo)), p Conclusion The 2G TKI as a first-line seem to be an effective option to reduce the treatment duration before TFR in CML pts although MRFS rate was not significantly improved in our study.