American Society of Hematology: Imatinib (Gleevec) and Dasatinib (Sprycel) in Chronic Myeloid Leukemia
Presenter: Neil Shah, MD, PhD, University of California, San Francisco, Comprehensive Cancer Center, San Francisco, California
The prognosis is poor for patients with chronic myeloid leukemia (CML) who are receiving imatinib (Gleevec, STI-571, Novartis) when their disease progresses to accelerated phase or blast-phase CML. In the START-R trial of CML, which compared imatinib doses, increased to 800 mg, against switching to dasatinib (Sprycel, Bristol-Myers Squibb), progression-free survival was greater for those receiving the newer drug, dasatinib.
Data from the International Randomized Study of Inter-feron versus STI-571 (IRIS) trial showed that about 31% of chronic-phase CML patients discontinued imatinib therapy within 4.5 years. About 50% of patients with chronic-phase CML stopped responding to treatment, or they progressed to accelerated-phase or blast-phase CML after 42 months. In addition, 15% of these patients who did not achieve a major cytogenetic response after 12 months of imatinib therapy had a significantly increased risk of disease progression. Although escalating the imatinib dose to 800 mg can be effective in patients with progressive disease, intolerance to the product and only brief periods of response are common.
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In Dr. Shah’s international, open-label, phase 2 trial, 150 chronic-phase CML patients with disease resistant to imatinib at doses of 400 to 600 mg were randomly assigned to receive, in a 2:1 fashion, dasatinib 70 mg twice daily or imatinib 800 mg. The median average daily doses were dasatinib 103 mg and imatinib 796 mg.
A higher percentage of dasatinib-treated patients achieved and maintained a major cytogenetic response, compared with the imatinib-treated patients. At three months, 36% of the dasatinib group had a major cytogenetic response, which increased to 53% at 15 months. With the high dose of imatinib, 29% of the patients had a major cytogenetic response at three months, compared with 33% at 15 months.
Major molecular remission was reported in 16% of the dasatinib patients, in contrast to 4% of the high-dose imatinib group. The median duration of response with dasatinib was 13.7 months; with imatinib, it was 3.1 months.
Complete cytogenetic responses (CCRs) with dasatinib occurred most often in patients who had previously experienced a CCR with imatinib therapy. Whereas CML in 10 of 49 patients progressed in the imatinib group, disease in six of 101 patients progressed in the dasatinib group (P< 0.0001).
Although non-hematological side effects were similar between the patient groups, grade 3 and 4 cytopenias were more common in the dasatinib group. Neutropenia was reported in 59% of patients receiving dasatinib and in 39% receiving imatinib; thrombocytopenia was reported in 55% of the dasatinib patients and in 14% of the imatinib patients. Grade 3-4 plural effusion and pulmonary edema were observed only in the dasatinib group, at low rates.
“The overall benefit-risk assessment favors dasatinib relative to imatinib 800 mg in this patient population,” Dr. Shah concluded.