On a Long Way to the Treatment Free Remisson: The Results of the Long-Term Observation of the Chronic Myeloid Leukemia Patients in Russian Part of EUTOS Population-Based Study
Authors: Lazareva Olga V. , Chelysheva Ekaterina Yu. , Kulikovsky Anton , Senderova Olga , Pepeliaeva Valentina , Meresiy Sergey , Luchinin Alexander S. , Milutina Galina , Gavrilova Lubov , Avdeeva Ludmila , Dasheeva Dolgorzhap , Vinogradova Olga , Kulikov Sergei M. , Turkina Anna G. 
Published: November 2019

Background: A success of the tyrosine kinase inhibitors (TKI) therapy in patients (pts) with chronic myeloid leukemia (CML) allowed to set a new goal: a treatment-free remission (TFR). A stable and long-lasting deep molecular response (DMR) is required for a successful TKI discontinuation. The number of CML pts with stable DMR increases on late terms of TKI therapy. With the relationship to this new goal it is relevant to evaluate the proportion of the potential candidates for TKI discontinuation in accordance with the country-specific features of the CML pts population in routine clinical practice.
Aim :To characterize the cohort of CML pts treated in routine clinical practice in Russian Federation and to evaluate the proportion of CML pts eligible for TFR.
Methods: The analyzed cohort consisted of 197 pts from 6 regions of Russia covering the population of 10 million inhabitants. All pts with CML diagnosed from 01.10.2009 to 31.12.2012 were included into the prospective multicenter EUTOS Population Based Study (EUTOS PBS). Median (Me) age was 50 (18-82)years, 49% were males. Chronic phase, accelerated phase and blast crisis was diagnosed in 93,4%, 6% and 0,6% pts respectively. Imatinib as a 1st line was used in 97% pts. The 2nd generation TKIs (TKI2) were used as 1st and 2nd -3rd line in 3% and 12% pts respectively; imatinib failure was the main reason of switch to TKI2.
Overall survival (OS) and cumulative (CI) of DMR were evaluated and adjusted to the new ELTS (EUTOS long-term-survival) score. A proportion of pts with sustained DMR eligible for TFR was calculated. DMR was considered as BCR-ABL<0,01% IS. A TFR eligibility was considered as a sustained DMR lasting for >2 years and TKI therapy >3 years.
Results:Me follow-up in Russian CML pts cohort of EUTOS PBS was 77 (0,7 - 107) months (mo). The ELTS score available in 179 pts was low, intermediate and high in 86(48%), 50(28%) and 43(24%) pts accordingly. The 7-year OS was 76% in total cohort (figure 1a). The 7-year OS in low, intermediate and high ELTS group was 87%, 68% and 55% respectively (p=0,001).
Me time of DMR achievement was 38mo (11,2 - 89 mo). The 7-year CI of DMR was 62%. The CI of 7-year DMR achievement in ELTS low, intermediate and high group was 62%, 42% and 38% respectively with significant difference between low and non-low score pts (p= 0,001) (figure 1b).
The data for the molecular response at data cut-off April 2019 were available in 114/123 pts who were alive and treated by TKIs with Me time 85 (range 65 - 105) mo. DMR, major molecular response (MMR, (BCR-ABL >0,01%- 0,1% IS) and no MMR (BCR-ABL> 0,1% IS) was in 76 (66,7%), 8 (7%) and 30 (26,3%) pts respectively. A sustained DMR was in 38 (50%) of 76 pts or 19% of the total cohort of 197 pts.
Conclusion: A significant proportion of CML pts reach a sustained DMR on late terms of TKI therapy. In total 19% of CML pts in Russian part of the EUTOS PBS study can be eligible to treatment-free observation after 7 years of TKI therapy. The low ELTS score predicts better survival and better chance of DMR achievement. The evaluation of the TFR perspective in routine clinical practicein important from diagnosis to late terms of treatment.

Disclosures
Chelysheva: Novartis: Consultancy, Honoraria; Fusion Pharma: Consultancy. Vinogradova:Novartis: Consultancy; Fusion Pharma: Consultancy. Turkina:Pfizer: Consultancy; Novartis: Consultancy, Speakers Bureau; fusion pharma: Consultancy; Novartis: Consultancy, Speakers Bureau; Bristol Myers Squibb: Consultancy.