Outcomes of Second-Line Treatment By Dasatinib in Imatinib-Resistant or -Intolerant Chronic Myeloid Leukemia Patients with and without Comorbidities

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.