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ATLANTA -- Using a lower dose of dasatinib (Sprycel) for the initial treatment of chronic myeloid leukemia (CML) in chronic phase was associated with similar disease outcomes but a lower risk for pleural effusion, a researcher reported here.

In a propensity score-matched analysis involving 154 patients, rates of pleural effusion were 5% for those started on a 50-mg dose of the second-generation BCR-ABL1 tyrosine kinase inhibitor versus 21% for those who received the standard 100-mg dose (P=0.016), including rates of grade 3/4 pleural effusion in 3% and 10%, respectively, reported Koji Sasaki, MD, PhD, of MD Anderson Cancer Center in Houston.

This was seen despite no difference in major clinical response or survival outcomes, according to the findings presented at the American Society of Hematology annual meeting.

"Low-dose dasatinib is as effective as standard-dose dasatinib, with less intolerance," said Sasaki. "This would be a good treatment option for low-risk patients." He noted that interpretation of the results is limited for high-risk patients.

Responses at 36 months -- complete cytogenetic response (CCyR), major molecular response (MMR), and cumulative incidence of MMR4 or MMR4.5 -- were similar or better in the 50-mg dasatinib group versus the 100-mg group, respectively:

• CCyR: 96% vs 88% (P=0.141)
• MMR: 92% vs 84% (P=0.234)
• MMR4: 77% vs 66% (P=0.038)
• MMR4.5: 77% vs 62% (P=0.021)

Failure-free survival was significantly higher in the low-dose group, with 4-year rates of 89% (95% CI 80.9-97.2%) compared with 77% (95% CI 67.7-86.7%) for the standard-dose group (P=0.041).

Other survival outcomes -- transformation-free survival (TFS), event-free survival (EFS), and overall survival (OS) -- were no different at 4 years between the two groups, respectively:

• TFS: 100% (95% CI 100-100%) vs 100% (95% CI 100-100%)
• EFS: 95% (95% CI 88.7-100%) vs 92% (95% CI 86.4-98.4%)
• OS: 97% (95% CI 93.4-100%) vs 96% (95% CI 91.9-100%)

Only 3% of patients on the lower dose stopped dasatinib within 12 months, as compared to 10% of those on the standard dose. Dose interruptions during that timeframe occurred in 7% and 52%. Cytopenia was the leading reason for dose interruptions, said Sasaki. Reductions were rare for those on the already-low dose but common among CML patients on the standard dose, leading to an average dose of 78 mg at 12 months in the latter group.

Other than pleural effusions, adverse events of any grade within 12 months of therapy were not significantly different between groups, though they tended to be numerically lower with the 50-mg dose.

"Given the lack of a randomized clinical trial of low-dose dasatinib compared to standard-dose dasatinib, frontline low-dose dasatinib can be considered," said Sasaki.

During a Q&A session following his presentation, however, a member of the audience pointed to a trial in the British Journal of Haematology that tested therapeutic drug monitoring for dasatinib in CML and included dose reductions for "overdosed" patients. The findings were in line with the current study. Among 80 randomized patients, cumulative incidence of pleural effusion was lower for the monitoring arm at 3 years (12% vs 39% in the control arm), while molecular responses were "superimposable" between the two arms.

Study Details

For their study, Sasaki's group analyzed data on 233 CML patients initially treated with either a 50-mg daily dose of dasatinib (n=83) or the standard 100-mg daily dose (n=150). Patients who received the lower dose had the option to increase their dose level to the standard dose if they had suboptimal responses by European LeukemiaNet 2013 criteria (only one of the patients did).

Of these, 77 patients from each group were matched 1:1 by propensity scoring. Rates of clonal evolution were 7% and 5% among the low-dose group and high-dose group, respectively. Most of the patients were low risk: Sokal risk group low (65% vs 69%), intermediate (29% vs 26%), and high (7% vs 5%).

No significant differences after matching were seen in median age (47 vs 49), spleen size (0 cm [0-12] vs 0 cm [0-16]), white blood cell count (35.7 vs 23.9 × 10⁶/L), hemoglobin (12.3 vs 12.0 × 10 g/L), platelets (344 vs 309), and percentages of basophil in peripheral blood (3% [0-15] vs 3% [0-19]), blasts in peripheral blood (0% [0-5] vs 0% [0-3]), or blasts in bone marrow (1% [0-9] vs 2% [0-8]).

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