Long-Term Outcomes of Dasatinib Therapy in Patients with Imatinib-Resistant or -Intolerant Chronic Myeloid Leukemia from Physician’s and Patient’s Perspective
Authors: Ionova Tatyana I , Nikitina Tatyana P , Fedorenko Denis A , Gritsenko Taras A , Ivanova Valentina L , Kuchma Galina B , Shnaider Tatyana V , Sannikova Inga V , Usacheva Elena I , Kurbatova Kira A 
Published: October 2019

Abstract
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.