کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5527702 | 1547885 | 2017 | 7 صفحه PDF | دانلود رایگان |
- Older AML patients need novel therapeutic agents, which proves a survival advantage.
- A goal when testing new drugs is to predict clinical responses by biomarkers.
- Low-dose lenalidomide and cytarabine combo induces 36.3% CR rate and improves OS.
- Based on the expression of 16 genes, we predicted CR with 88% overall accuracy.
- In this combo CR was efficiently predicted by GEP.
Outcome for elderly patients with acute myeloid leukemia (AML) is extremely poor. Intensive induction chemotherapy is often unsuitable. Sixty-six newly diagnosed AML patients (median age: 76Â years), ineligible for standard therapy, were consecutively treated with low-dose lenalidomide (10Â mg/day orally, days 1-21) plus 10Â mg/m2 low-dose cytarabine, subcutaneously, twice a day (days 1-15) every six weeks, up to 6 cycles. Complete remission (CR) rate was 36.3% according to intention-to-treat. Responding patients had a longer median overall survival than non-responders (517 vs. 70Â days, PÂ <Â 0.001). The achievement of CR was not predicted by bone marrow blast count, cytogenetics, molecular markers, prior MDS, white blood cell count. Conversely, by studying the global gene expression profile, we identified a molecular signature, including 309 genes associated with clinical response (CR versus no CR). Based on the expression of a minimal set of 16 genes, we developed an algorithm to predict treatment response, that was successfully validated by showing an overall accuracy of 88%. We met the primary endpoint of the study, by beating the estimated successful CR rate (P1) fixed at 30%. Moreover, CR induced by this 2-drug combo was efficiently predicted by genetic profiling, identifying a biomarker that warrants validation in independent series.
Journal: Leukemia Research - Volume 62, November 2017, Pages 77-83