CML-083: Prognostic Factors of Durable Treatment-Free Remission in CML Patients Based on the Prospective Study RU-SKI

Abstract

Aim To define the prognostic factors for molecular relapse-free survival (MRFS) after TKI discontinuation in the Russian CML population. Methods The base for the analysis was the Russian multicenter prospective study RU-SKI on the discontinuation of TKI in patients (pts) with CML and deep molecular response (DMR). Ninety-eight CML pts with chronic-phase, TKI therapy for at least three years and a stable DMR (BCR-ABL Results Three-year MRFS rate was 51%. Baseline pts characteristics: male - 50%; median (Me) age at TKI cessation 46 years (range, 22 to 80); Me duration of TKI therapy 8.3 years (range, 3 to 16.2); Me duration of DMR 3.2 years (range, 2 to 10.7). Therapy before treatment cessation: imatinib in 67 (68.4%) pts, second-generation (2G) TKI in 31 (31.6%) pts. Me follow-up time after TKI cessation was 40 mo (range, 28 to 57). Probability of MRFS (1st stop) was 53% after 36 mo of follow-up. Length of DMR, duration of therapy and depth of molecular response were found to be significant factors with p ≤ 0.05. We have found that the duration of TKI therapy, and not the duration of DMR, has an independent prognostic value for the Russian CML population due to the lack of molecular monitoring data at early stages of the disease. No difference in 36 months MRFS was observed in 1st-line imatinib (55%) compared with 1st-line 2G TKI (70%; p=0.26) and 2nd-line 2G TKI (39%; p=0,09) groups. However, significantly shorter treatment duration was observed in pts treated with 1st-line 2G TKI (Me=41.5 mo) vs imatinib (Me=96.4 mo), p Conclusion Longer treatment duration and depth of DMR before cancellation at least MR 4.5 are associated with durable TFR. Our study showed that the MRFS rate is not significantly improved with the use of 1st-line 2G TKI in comparison with 1st-line imatinib.