Background:The data of 2904 adult patients (pts) with newly diagnosed chronic myeloid leukemia (CML) from 20 European countries were included into the multicenter EUTOS ELN population‐based Study (EUTOS PBS) from 2008 to December 2012 (Hoffman V et al. 2016). Russia took part in the EUTOS PBS and included 6.8% of the total number of pts. The EUTOS PBS in Russian Federation was prolonged and the results were updated at a long‐term follow‐up.Aims:To evaluate the long‐term results of treatment in pts with newly diagnosed CML in EUTOS PBS in Russia.Methods:The analyzed cohort of 197 pts (18 years) with Ph’+ /BCR‐ABL1+CML diagnosed in period 10/01/2009 ‐ 31/12/2012 from 6 regions of Russia was included into EUTOS PBS. CML was diagnosed in chronic phase (CP), accelerated phase (AP) and blast crisis (BC) in93,4%, 6% and 0,6%pts respectively. The ELTS low, intermediate and high score(n = 179)was in 86 (48%), 50 (28%) and 43 (24%) pts accordingly. Median (Me) age was 50 (18–82) years, the male/female ratio was equal. The overall survival (OS) considering CML phase, cumulative incidence (CI) of deaths depending on death reasons was analysed. The CI of complete cytogenetic response (CCyR) and major molecular response (MMR) was evaluated. All calculations were done using the SAS Version 9.4 package of procedures program.Results:Me follow‐up in the Russian part of EUTOS PBS was 69 (0,7 – 96) months (mo). Imatinib (IM) and 2ndgeneration tyrosine kinase inhibitors (TKI2) were used as 1stline therapy in 97% and 3% pts accordingly. The 5 years CI of CCyR and MMR at the 1stline TKI therapy was 83% and 67% accordingly. The switch to the 2ndand 3rdline of TKI2 therapy was in 22 (12%) of 193 pts, the main reason was IM failure.The OS by 5, 6 and 7 years was 80% (95% CI 72% ‐ 86%), 78% (95% CI 65% ‐ 80%) and 73% (95% CI 65% ‐ 80%) respectively in total cohort (p < 0,001). The OS of pts with low and high ELTS score was 88% and 56% (p < 0,0023) respectively by the 80 mo of follow‐up. The 5‐year OS in pts with AP+BC phase was 39%.In total 47 (23,8%) pts died during the whole observation period. The largest number of deaths was observed in the 1styear after the CML diagnosis: 17 (36%) of 47 cases. The death reasons were as follows: 1) progression of CML to AP/BC in 20 (43%) pts, 2) death in remission (pts with CCyR and /or MMR within 6 months before death) in 5 (11%) pts, 3) death without progression to AP/BC but with signs of leukemia and without CCyR in 22 (46%) patients. The 5 years CI of death from all reasons was 20%, CI of CML‐related and CML non‐related death at 5thyear was 18% and 11% respectively (figure1).Summary/Conclusion:In general, the results of therapy in CML pts of the Russian non‐selected population sample were comparable to the data of the whole European cohort. A higher proportion of pts with ELTS high ELTS scoreand a lower proportion of pts switched to 2nd/3rdline TKI therapy in comparison with Europe was identified. These issues could have an impact on the number of CML‐related deaths and their high proportion in the 1styear of therapy. Therefore, the early therapy interventions within the 1styear of therapy in CML pts are apparently important for the long‐term treatment results.image
Introduction and data: Social and demographic personal data are important to be included in analysis and interpretation of results of any population studies in oncology. But it looks like social status is underestimated as cofounder for survival of patients with chronic myeloid leukemia (CML). The aim of this study was to check the prognostic value of social parameters like marital status and education level in comparison with standard risk factors. Russian CML Registry include more than 10 thousand patients (pts) data. In the analysis 8326 CML pts in chronic phase (CP) with first line TKI therapy were included: 91% of pts were treated by Imatinib and 9% by other TKIs. Mean age was 49years, 4607 f/ 3705 m. Me of follow-up-4.24years. Overall survival(OS) was estimated starting the diagnosis date, event was death from any reason, date of last contact was censored for alive pts. Survival analysis was performed by SAS procedures. Results:Firstly, we perform one-way survival analysis and estimate OS depending upon the 3 parameters Sokal Score, Marital Status and Education. There are high significant dependences OS on all three factors as shown on picture 1 (OS estimates depending on values of: 1A) Sokal score (low, intermediate, high), 1B) Marital Status (married, single, widowed/divorced), 1C) Education (low/secondary, higher). Marital Status and Education are correlated with Sokal Score (corresponding Pearson's coefficients are 0.19 and 0.12, p<0.0001). This association is caused by age but is not so strong. Than we have estimate OS in each Sokal's risk groups (picture 2. OS estimates depending on Marital Status (single, married - blue line, widowed/divorced - green line) in different Sokal's risk groups: 2A) - low, 2B) - intermediate, 2C) - high). OS estimates depending on Education (picture 3; (low/secondary red line, higher- blue line) in different Sokal's risk groups: 3A) low, 3B) intermediate, 3C) high. And we see that Marital Status and Education are predictive in each risk group but the most influent in high risk group. Marital Status and Education are correlated with other impotent cofounder- age. It should be checked in additional multi factor analysis we plan to do. We also run the proportional risk regression Cox's model on this data. Hazard ratio (HR) and significance (Px2) for included parameters are following: Sokal score - HR=1.59, Px2<0.0001; Education- HR=1.76, Px2<0.0001; Marital Status- HR=1.40, Px2<0.0006. Conclusions: The social and demographic personal data should be included in any analysis of CML population data. Marital Status and Educationare obviously associated with adherence behavior of CML patients and must influent on longitude therapy output. The highly education level is favorable factor, widowed/divorced marital status is unfavorable factor for OS prognosis. Figure. Figure. Disclosures Kulikov: Russian Foundation for Basic Research grant 18-015-00399 A: Research Funding. Turkina:Novartis: Other: provided consultations; Bristol Myers Squibb: Other: provided consultations; Phizer: Other: provided consultations; Fusion Pharma: Other: provided consultations.
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.
The results of long-term follow-up of patients (pts) with chronic myeloid leukemia (CML) do not lose their importance. Data from routine clinical practice are of particular interest. The use of 1 st (imatinib, IM) and 2nd generation TKI (2G TKI) led to a significant increase in survival, so the probability of death associated with CML could be significantly lower than the probability of death due to common causes of death other than CML. To analyze the overall survival (OS) and causes of mortality in CML pts treated in routine clinical practice in Russian Federation for a long period (>15 years) of time. The long-term follow-up data of the Russian part of the European LeukemiaNet (ELN) OSP EUTOS multicenter observational study were evaluated. The analyzed cohort consisted of 678 Ph/BCR-ABL-positive CML pts from 35 regions of Russia diagnosed in 2002-2006 with IM therapy initiation ≤6 months (mo) after diagnosis. Median (Me) age was 47(range 18-81) years (y), 47% males. Chronic phase, accelerated phase and blast crisis at diagnosis was in 631 (93%), 41(6%) and 6(1%) pts, respectively. The annual number of newly diagnosed pts was as follows: 2002 - 15 pts, 2003 - 38 pts, 2004 - 46 pts, 2005 - 206 pts, 2006 - 302 pts. The last update for 209 pts was done in Jun. 2021; last contact for 100 pts - in 2020, for 39pts - in 2019, for the other - before 2018. The date of the last contact/death could not be established for 14 pts. Statistical analysis included 661 pts, the OS was evaluated by Kaplan-Mayer method using the SAS 9.4 package. In total, 331 (50%) pts of the analyzed cohort were alive with the Me follow-up of 180 (range 2-232) mo or 15 y (range 2 mo-19,3 y). All pts started therapy with IM with 25% switched to 2G TKI in subsequent therapy lines. In total, 218 (66%) pts achieved MR4, 183 (55%) pts got MMR; 46 (21%) of these pts with deep molecular response (DMR) were observed in hematology centers of Moscow. The 15-y OS in the total cohort was 63% (CI 59-70%)(fig.1). The OS by age groups was as follows: 18-40yy-75% (CI 73-82%), 40-60yy- 63% (CI 59-70%), 60-80yy- 37% (CI 30-45%). The most complete information was provided by Moscow centers (2 centers, 113 pts). The 15-y OS of pts receiving treatment in Moscow was significantly higher vs pts from other regions (32 centers, 548 pts): 75% vs 60%, p=0,0030 (fig.2). The mortality in the whole cohort of 661 pts was 35% (233 pts). Of these 233 pts, 112(48%) pts deaths were due to CML progression to AP or BP (including non-compliant cases); 3pts (1,5%) died after allogenic stem cell transplantation (infection complications); the cause of death was unknown in 50 (21,5%) pts. The highest death rate from CML progression was at 4-9 y of follow-up. Deaths caused by concomitant diseases were in 68 (29%) pts: coronary artery disease/myocardial infarction/heart failure in 42 (62%) of 68 pts, acute ischemic stroke in 10 (15%) pts, second malignancies (Cr- cancer) in 10 (15%) pts (lung tumor, metastatic esophageal Cr, stomach Cr, brain tumor, sigmoid colon Cr, rectal colon Cr, melanoma, renal Cr, breast tumor, other hematological malignancies), accidents - 1 pt, liver cirrhosis - 2 pts, in 2 cases - respiratory virus infections complicated with pneumonia, 1 pt died due to Covid-19. Conclusions. The long-term follow-up of the multicenter study EUTOS OSP in 35 regions of Russian Federation allows not only to characterize the 15-y OS in CML pts but also provides the long-term outlook of the routine clinical practice. Probably, better OS of CML patients receiving treatment in Moscow (2 centers) may be related to organizational issues of interaction with the federal center, better monitoring and timely switching to 2G TKI therapy. The organization and support of multicenter studies may improve the situation with the treatment of diseases of the blood system. Figure 1 Figure 1. Disclosures Chelysheva: Novartis Pharma: Speakers Bureau; Pfizer: Speakers Bureau; Pharmstandart: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Vinogradova: Pharmstandart: Speakers Bureau; Novartis Pharma: Speakers Bureau; Pfizer: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Lomaia: Novartis: Honoraria; Pfizer: Honoraria; BMS: Honoraria; Pharmstandard: Honoraria. Voloshin: Abbvie: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Astra Zeneca: Consultancy, Speakers Bureau; Pfizer: Consultancy; Biacad: Consultancy, Speakers Bureau. Turkina: Pharmstandart: Speakers Bureau; Pfizer: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; Novartis Pharma: Speakers Bureau.
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