In a French randomized phase II trial reported in the Journal of Clinical Oncology, Thomas et al found that clofarabine-based consolidation may provide improved relapse-free survival vs conventional high-dose cytarabine in postremission treatment in younger patients with acute myeloid leukemia (AML) and no identified donor for allogeneic stem cell transplantation (SCT). Hervé Dombret, MD, of Hôpital Saint-Louis, Paris, is the corresponding author of the Journal of Clinical Oncology article.
In the open-label trial, 221 patients aged 18 to 59 years old with intermediate- or unfavorable-risk AML in first remission from 33 French centers were randomized between March 2009 and September 2013 to receive 3 consolidation cycles with clofarabine (Clolar) at 30 mg/m2/d on days 2 to 6 and cytarabine at 1 g/m2/d by bolus infusion over 2 hours on days 1 to 5, with granulocyte colony-stimulating factor (G-CSF) priming (n = 107) or cytarabine at 3 g/m2/12 hours on days 1, 3, and 5 with G-CSF priming (n = 114). The primary endpoint was relapse-free survival.
Key Findings
At 2 years, relapse-free survival was 58.5% in the clofarabine group vs 46.5% in the cytarabine group (unadjusted hazard ratio [HR] = 0.76, P = .13). Overall, 110 patients (55 in each group) received SCT in first remission after late donor identification.
In a multivariable Cox-adjusted treatment by SCT interaction analysis, the hazard ratio for relapse-free survival before or in the absence of SCT for clofarabine-based vs cytarabine treatment was 0.65 (P = .041). In a sensitivity analysis censoring patients receiving SCT at the time of SCT, 2-year relapse-free survival rates were 53.3% vs 31.0% (HR = 0.63, P = .043).
The cumulative 2-year incidence of relapse was lower in the clofarabine group (33.9% vs 46.4%, HR = 0.61, P = .025). Two-year relapse-free survival was similar among patients receiving SCT (65.8% vs 62.9%). Hematologic and nonhematologic toxicities were greater with clofarabine-based treatment.
The investigators concluded: “These results suggest that [clofarabine-based treatment] might be considered as a new chemotherapy option in younger patients with AML in first remission.”
Thomas X, et al: J Clin Oncol 35:1223-1230, 2017. ■
