PS1177 PROGNOSTIC FACTORS FOR MOLECULAR RELAPSE‐FREE SURVIVAL AFTER DISCONTINUATION OF TYROSINE KINASE INHIBITORS IN CHRONIC MYELOID LEUKEMIA BASED ON RUSSIAN MULTICENTER PROSPECTIVE TRIAL (RU‐SKI)
Authors: Shukhov O. , Chelysheva E. , Petrova A. , Bykova A. , Nemchenko I. , Turkina A. 
Published: June 2019

Background:

About 50% of chronic myeloid leukemia (CML) patients (pts) after TKI discontinuation lose a major molecular response (MMR) and should return to therapy. Despite the fact that, after TKI resumption, almost all pts re‐achieve deep molecular remission, facilitating a more accurate selection process for therapy cessation remains topical

Aims:

To define the prognostic factors for molecular relapse‐free survival after TKI discontinuation in Russian CML population

Methods:

The base for the analysis was the Russian multicenter prospective study RU‐SKI on the discontinuation of TKI in pts with CML and deep molecular response (DMR). Ninety‐eight CML pts with chronic phase (CP), TKI therapy for at least three years and a stable DMR (BCR‐ABL<0.01%) for at least two years were enrolled. Pts with previous imatinib failure and treatment‐free remission (TFR) failure were eligible. The BCR‐ABL level was evaluated by RQ‐PCR according to the international scale (IS). The schedule of molecular tests was as follows: monthly during the first six months (mo) after TKI cessation, every two mo from six to 12 mo and every three mo thereafter. Treatment by the same TKI was resumed in case of MMR loss (BCR‐ABL>0.1%). We used the proportional hazards regression analysis to identify independently significant factors for molecular relapse‐free survival (MRFS). We categorized each independently significant factor into two groups, depending on the optimal cutoff level obtained by the minimum P‐value approach. We used the Kaplan‐Meier method for calculating the probability of MRFS and the log‐rank test for comparison.

Results:

One year MRFS in all group was 51%. MRFS rate in pts with history of previous TFR failure (n = 7) was 14%. We decided to exclude from multivariate analysis pts with history of previous TFR failure to identify significant factors for the first attempt of therapy cancellation. Baseline pts characteristics (1st stop, n = 91): male: 48%; median (Me) age at TKI cessation 46 years (range 22 to 80); Me duration of TKI therapy 8.3 years (range three to 16.2); Me duration of DMR 3.2 years (range two to 10.7). Therapy before treatment cessation: imatinib in 63 (69%) pts, second‐generation (2G) TKI in 28 (31%) pts. Me follow‐up time after TKI cessation was 24 mo (range 12 to 41). Probability of MRFS (1st stop) was 55% after 12 mo of follow‐up. We include in multivariate analysis the following factors: age, gender, history of previous resistance to imatinib, type and line of TKI, duration of therapy, length of DMR, depth of molecular response before cancellation, Sokal risk group. Sokal risk group, duration of therapy and depth of molecular response were found to be independently significant factors with p ≤0.05. Treatment duration more than 8 years, depth of DMR before cancellation at least MR4.5, non‐high Sokal risk group were attributed to favorable factors for MRFS after the optimal cutoff level was obtained (fig.1). 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. The lack of molecular monitoring data at early stages of the disease in long‐term treated pts cause to the 1st DMR detection bias. Indeed, a longer time to the 1st DMR was observed in pts with the longer duration of TKI therapy (fig.2).

Summary/Conclusion:

Patients with treatment duration more than 8 years, depth of DMR before cancellation at least MR4.5, non‐high Sokal risk group and without history of previous TFR failure are more preferable for TKI discontinuation

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