Abstract
Chronic, low-grade adverse events are common in patients with chronic myeloid leukemia who are treated with imatinib. These events may decrease patient quality of life and adherence, and may ultimately contribute to a suboptimal response. Alternative, second-generation tyrosine kinase inhibitors, such as dasatinib, are available with the potential to reduce adverse events, improve tolerability, and support long-term treatment goals. We present the final, primary analysis of DASPERSE/CA180-400 (NCT01660906), an open-label, multicenter, phase IV study designed to determine whether chronic, low-grade nonhematologic adverse events in imatinib-treated patients improve after switching to dasatinib, without affecting efficacy. Of the 121 chronic, grade 1/2, imatinib-related adverse events identified at baseline in 39 patients, 77% resolved or improved within 3 months after switching to dasatinib. Dasatinib maintained a consistent safety profile; headache (33%), pleural effusion (26%), fatigue (23%), and rash (23%) were the most common treatment-related adverse events after the switch. Patients either maintained (56%) or improved (44%) their molecular response on dasatinib. Patients who switched to dasatinib also experienced improved patient-reported symptom burden from baseline as assessed by the MD Anderson Symptom Inventory for chronic myeloid leukemia (on a 1–10 scale, mean change in disease-specific score was − 2.24 and core symptom severity score was − 1.06). Overall, the efficacy and quality of life/symptom burden improved in many patients, despite the onset of dasatinib-related adverse events in most patients. This suggests that imatinib-treated patients with chronic, low-grade adverse events could benefit from switching to treatment with dasatinib.
Highlights
Patients diagnosed with chronic myeloid leukemia (CML) in chronic phase (CP) and treated with imatinib often experience chronic, low-grade adverse events (AEs) that may negatively impact their quality of life and their ability to remain on longterm therapy [1,2,3,4,5]
A total of 39 patients with CML-CP and prior imatinib treatment were enrolled between December 7, 2012 and October 1, 2015
The DASPERSE study aimed to determine whether chronic, grade 1/2 AEs that occurred as a result of imatinib treatment would resolve or improve if patients with CML were switched to the second-generation tyrosine kinase inhibitor (TKI) dasatinib
Summary
Patients diagnosed with chronic myeloid leukemia (CML) in chronic phase (CP) and treated with imatinib often experience chronic, low-grade adverse events (AEs) that may negatively impact their quality of life and their ability to remain on longterm therapy [1,2,3,4,5]. Results from the Imatinib Long-Term Side Effects study reported that more than half of patients with CML who were being treated with imatinib have at least one nonserious AE after a median treatment period of 5.8 years, and that nonserious AEs increased over time, from 34.3% at 6 years to 52.6% at 8 years [4]. Differences in TKI structure and binding can lead to distinct safety profiles for each drug [9, 10, 12]; for example, pleural effusion occurs with higher incidence in patients treated with dasatinib versus imatinib, and facial edema, muscle spasms, myalgia, nausea, and vomiting are reported more frequently with imatinib versus dasatinib [13, 14]. Among the BCR-ABL1 TKIs, pulmonary arterial hypertension (PAH) has been mainly associated with dasatinib, it is rare and often reversible upon dose reduction/interruption [9, 10]
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