Clinical and Patient-Reported Outcomes of Dasatinib Therapy in Patients with Imatinib-Resistant or -Intolerant Chronic Myeloid Leukemia

Abstract 4445

Despite remarkable responses with imatinib in chronic phase chronic myeloid leukemia (CML-CP), there remains a proportion of patients who are resistant or intolerant to imatinib treatment. Dasatinib is effective second-line treatment for this patient population. Importantly, without effective therapeutic intervention, these patients inevitably progress to advanced phases of disease, have a short survival and declined health outcomes. This emphasizes the importance of patient-reported outcome assessment in these patients. Comprehensive information about the results of dasatinib therapy both in terms of clinical and patient-reported outcomes will be helpful in evaluation of risks/benefits of treatment in this patient population. We aimed to study response rates as well as quality of life (QoL) parameters and symptom profile in imatinib-resistant or -intolerant CML-CP patients receiving dasatinib.

38 CML-CP patients resistant or -intolerant to imatinib were enrolled in the study (mean age - 50 years old, SD 14.5; range −22–79 years; male/female – 19/19). The median of disease duration was 5.7 years (1–13 years). The median duration of imatinib treatment - 39 months (5–101 months). 33 patients had resistance to imatinib treatment; 5 patients were intolerant to imatinib. Patients received dasatinib in the dose of 100 mg daily. Median follow-up was 12 months. For QoL assessment patients filled out the SF-36 and for symptom assessment – Comprehensive Symptom Profile in Chronic Myeloid Leukemia Patients (CSP Leuk-CML). The CSP Leuk-CML is developed to assess profile of 47 symptoms specific for patients with CML. To compare patient population with normative data the sample from population norm (PN) database adjusted to age and gender was used. For comparisons Mann-Whitney test was used. Symptom severity and percentages of patients with symptoms at moderate-to-severe (ratings³ 5) levels was evaluated.

High rates of hematologic (complete, 90%) and cytogenetic (major, 85%; complete, 35%) response were observed for the majority of patients at 6 months from the start of therapy. During observation period two patients died (at 2 and 6 months after therapy initiation), one patient discontinued treatment due to significant thrombocytopenia at 2 months, and one patient discontinued treatment due to disease progression at 6 months after therapy initiation. At base-line patients experienced impaired QoL as compared to population norms: the values for the majority of SF-36 scales were significantly lower than in control group (p<0.05). No QoL impairment was observed in 35% of patients. 25% of patients had either mild (Integral QoL index <25% decrease from a PN) or moderate (25–50% decrease from a PN) QoL impairment; other 20% of patients - severe QoL impairment (50–75% decrease from a PN), and 20% of patients - critical QoL impairment (>75% decrease from a PN). At base-line the majority of patients (96%) experienced fatigue; a half of them suffered from moderate-to-severe fatigue. 75% of patients experienced at least one moderate-to-severe symptom; more than 40% had more than 7 moderate-to-severe symptoms. At 12 months after dasatinib treatment 47% of patients experienced no QoL impairment; the number of patients with severe or critical QoL impairment slightly decreased (25% and 10%, respectively). At 12 months after the start of therapy QoL treatment response in terms of stabilization or improvement was registered in the majority of patients (81%). In nearly all patients symptom severity did not change or became lower at different time-points of treatment as compared with base-line. The number of patients with moderate-to-severe symptoms decreased while treatment.

Thus, treatment with dasatinib is beneficial for imatinib-resistant or -intolerant CML-CP patients both in terms of clinical and patient-reported outcomes. Desirable clinical and patient-reported outcomes were registered for the majority of patients. Comprehensive evaluation of the results of second-line treatment of CML-CP allows to assess the risks and benefits of therapy both from physician's and patient's perspective.