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Background. Due to the significant increase in life expectancy and the quality of life in patients with chronic myeloid leukemia (CML) as well as the growing need for expensive tyrosine kinase inhibitors (TKI), the analysis of cost-effectiveness and lifelong monitoring of patients is especially important. Aim. We present the results of a multicenter observational study “The Russian Registry of Chronic Myeloid Leukemia in routine clinical practice (2011-2016)”. Materials & Methods. The study included Russian patients with CML, confirmed by the detection of a Ph-chromosome or a BCR-ABL transcript. The statistical analysis (July 1, 2016) included 7609 patients from 80 regions of the Russian Federation (covering 95 % of the population). The annual increase in the number of patients with newly diagnosed CML was 600-650 patients. At the time of the statistical analysis, 6995 (92 %) patients remained under observation, 473 (6 %) died and 141 (2 %) were withdrawn. The registry included 44 % of men and 56 % of women, the median age was 49 years (range 2-94 years). The peak incidence (46.3 %) occurred at the age of 40-60 years. The median disease duration by the time of the analysis was 6 years (range 0.1-30 years). Results. The disease was diagnosed in the chronic phase (CP), acceleration phase, and blast crisis in 6560 (93.8 %), 380 (5.5 %) and 47 (0.7 %) patients, respectively. The proportion of risk groups according to Sokal for low, intermediate and high risk in CP was 49 %, 30 %, and 21 %, respectively. TKI were administered to 6473 (92.5 %) patients. Imatinib and the second generation TKI (TKI2) were administered to 5570 (86 %) and 903 (14 %) patients, respectively. The total of 30.4 % of patients received the increased imatinib dose of 600-800 mg. In the TKI2 group, 558 (61.7 %) patients received nilotinib and 345 (38.2 %) patients received dasatinib. The proportion of patients with completed molecular genetic studies (MGS) in 2014, 2015 and the first 6 months of 2016 amounted to 61 %, 58 % and 23 %, respectively. The proportion of patients with cytogenetic studies (CS) for the same period was 28 %, 26 % and 7 %, respectively. No CS or MGS data were presented for 34 %, 35 % and 63 % of patients during this period. Optimal molecular response and major molecular response (MMR) for TKI therapy were observed in 23 % and 58 % of patients treated < 12 months and > 12 months, respectively. When nilotinib was used in the second line, MMR was obtained in 42 % of patients, and a deep molecular response was obtained in 25 % of patients (BCR-ABL < 0.01 %). Conclusion. The high efficacy of TKI therapy was observed in the majority of patients with the possibility of achieving a minimal residual disease. The problems concerning untimely monitoring and suboptimal administration of second line treatment were identified. In general, the CML patient registry allowed the data integration of data and information management of population with CML in Russia.

Patients in chronic phase chronic myeloid leukemia (CML-CP) with comorbidities may have reduced overall survival and worse safety of TKI treatment as compared in those without comorbidities. Dasatinib is a promising treatment option for CML-CP patients resistant or -intolerant to imatinib. Benefits and risks of this treatment regimen might be dependent on the presence of comorbidity. We aimed to study clinical outcomes, safety and QoL in CML-CP patients with and without comorbidities receiving dasatinib as second-line treatment in a "real-world" setting. 30 CML-CP patients resistant or -intolerant to imatinib were enrolled in multicenter prospective observational real-world study (mean age 48 years old, SD 13.1; range 22-60 years; male/female - 14/16). All the patients received dasatinib as the second-line therapy (100 mg daily) during 18 months. Ten patients exhibited comorbidities: Charlson Comorbidity Index varied from 1 to 5. Treatment outcomes were evaluated at 18 months of dasatinib therapy. For QoL assessment patients filled out SF-36 questionnaire before and 18 months after dasatinib treatment start. Group comparisons were made using t-test. Clinically significant differences were analyzed by computing Effect Size (ES). At 18 months of dasatinib treatment there were no statistically significant differences in clinical response between the groups with and without comorbidities: complete hematologic response was observed in 90 and 95% patients, respectively; complete cytogenetic response - in 80 and 55% patients, respectively; molecular response - in 60% patients in both groups (complete molecular response - in 50 and 25% patients, respectively; major molecular response - in 10 and 35% patients, respectively). In the group with comorbidities 2 patients had severe adverse effects (SAE) at 18 months of treatment: headache, hyperglycemia, pleural effusion, visual problems, neuropathy, memory loss, diarrhea, visual problems. In the group without comorbidities 5 patients exhibited SAE at 18 months of treatment: fatigue, memory loss, headache, neutropenia, sleepless. QoL before dasatinib treatment was more impaired in the group with comorbidities than in patients without comorbidities: physical functioning - 57.8 vs 80.4 (p=0.01, ES=0.89), Integral QoL index - 0.29 vs 0.44 (ES=0.75). After 18 months of dasatinib treatment QoL improvement or stabilization was registered in both groups as compared with base-line. Patients without comorbidities had significant improvement of role physical functioning (55 vs 82.5, p=0.01), vitality (59 vs 73, p<0.01), role emotional functioning (70 vs 86.7, p=0.02), mental health (62.0 vs 76.8, p=0.01); Integral QoL index significantly increased during treatment as compared with base-line (0.44 vs 0.6, p<0.01). Patients with comorbidities exhibited pronounced improvement of physical functioning during treatment (57.8 vs 69, ES=0.57); no changes in other QoL domains and Integral QoL index were observed. Thus, outcomes of second-line treatment by dasatinib in CML-CP patients with and without comorbidities were studied a "real world"setting. Clinical outcomes and safety profile were similar in patients with and without comorbidities. After 18 months of dasatinib treatment definite QoL improvement was registered in patients without comorbidities and QoL stabilization - in patients with comorbidities. Assessment of the outcomes of second-line therapy by dasatinib in CML-CP both from physician's and patient's perspective allows provide to comprehensive evaluation of benefits and risks of treatment in this heterogeneous patient population. Disclosures No relevant conflicts of interest to declare.

Information about the efficacy and safety of the second-line therapy with dasatinib in patients in chronic phase chronic myeloid leukemia (CML-CP) at long-term follow-up is limited. Evaluation of benefits and risks of the treatment in a “real-world” study both from physician’s and patient’s perspective is worthwhile to better define treatment outcomes in this patients’ population. We aimed to study clinical and patient-reported outcomes as well as safety of the second-line therapy by dasatinib in CML-CP patients with imatinib resistance or intolerance treatment at long-term follow-up. 75 CML-CP patients resistant or -intolerant to imatinib were enrolled in the prospective, multicenter, non-interventional study (mean age 51.3 years old, SD 15.4; range 22–83 years; male/female – 37/38). All the patients received dasatinib as the second-line therapy (100 mg daily). Clinical and patient-reported outcomes were evaluated at base-line, 12, 18 and 24 months after treatment start. Twenty six patients were analyzed through all study time-points. For quality of life (QoL) and symptom assessment all the patients filled out the SF-36 and Comprehensive Symptom Profile in Chronic Myeloid Leukemia Patients (CSP Leuk-CML), respectively. Overall and progression-free survival rates as well as cumulative probability of achieving a complete cytogenetic response (CCgR) were calculated using Kaplan-Meier methods. To compare frequencies of CCgR χ2 criterion was applied. Comparison of QoL and symptom scores was conducted using t-test. QoL scores were analyzed using t-test, adjusting for sociodemographic and disease status. At 24 months of dasatinib treatment 94% patients achieved or maintained complete hematologic response and 69% – CCgR. The twenty four-month progression free survival rate was 79% (95% CI; 63.3–88%), overall survival rate – 93% (95% CI; 84–97%). One patient was resistant to dasatinib after 16 months of treatment. During the second year of dasatinib therapy one сase of pleural effusion (grade 3) was registered (at 18 months of treatment); other severe adverse effects (grade 4) were as follows: one patient – neutropenia (at 18 months), one patient – arthralgia/myalgia (at 18 months), one patient – memory loss (at 24 months), one patient – headache and hyperglycemia at 18 months and palpitations, alopecia, hyperglycemia at 24 months of treatment. At 24 months of dasatinib treatment improvement of QoL as compared with base-line was registered: Integral QoL index was significantly higher than at base-line (p<0.02). At 24 months follow-up the proportion of patients with no QoL impairment was 56%; 18.7% patients exhibited severe/critical QoL impairment. It was shown that 56.4% patients with no/mild QoL impairment before dasatinib treatment (favorable group) achieved CCgR as compared with 28% patients with severe/critical QoL impairment (unfavorable group). Progression-free survival rate was 87% in the favorable group vs 60% in the unfavorable group. Cumulative probability of CCgR achievement was higher in the favorable group vs the unfavorable group – 75% vs 50% (log-rank test, p<0.05). Thus, long-term outcomes of second-line therapy in CML-CP patients in a “real world” setting confirm that dasatinib treatment is effective both in terms of clinical outcomes and patient-reported outcomes, as well as exhibits good tolerability. At 24 months of treatment definite QoL improvement was registered. Patients with high QoL before second-line treatment have had better treatment outcomes at long-term follow-up. Comprehensive evaluation of the outcomes of the second-line treatment of CML-CP at long-term follow-up allows to assess the benefits and risks of therapy both from physician’s and patient’s perspective. Disclosures Ionova: BMS: Research Funding. Nikitina:BMS: Research Funding. Fedorenko:BMS: Research Funding. Gritsenko:BMS: Research Funding. Ivanova:BMS: Research Funding. Kuchma:BMS: Research Funding. Shnaider:BMS: Research Funding. Sannikova:BMS: Research Funding. Usacheva:BMS: Research Funding. Kurbatova:BMS: Research Funding.