Clofarabine-Based Consolidation in Younger Adults with AML in First Remission: Results of the Randomized ALFA-0702/CLARA Study
The randomized ALFA-0702/CLARA study is evaluating the CLARA combination of clofarabine plus intermediate-dose cytarabine versus high-dose cytarabine (HiDAC) as consolidation cycles in younger patients with unfavorable acute myeloid leukemia (AML); Thomas and colleagues reported preliminary results of this trial.1 In this French trial, a total of 713 patients aged ?60 years with de novo AML were enrolled, and treated with induction therapy of standard daunorubicin and cytarabine. Eligible patients in complete response (CR)/CR with incomplete platelet recovery (CRp) underwent allogeneic stem-cell transplantation (SCT) if eligible or randomized to receive consolidation therapy with high-dose cytarabine or the CLARA regimen.
Of the 468 patients who achieved a CR/CRp, 221 were randomized to HiDAC (n = 114) and CLARA (n = 107) consolidation; 247 (53%) patients were not randomized, mainly because of SCT eligibility (n = 181). In the intent-to-treat population (n = 221), the median age was 48 years, and 136 had intermediate-risk and 85 had unfavorable-risk AML. Of these, 50% of the patients were eligible for SCT in first remission. At a median follow-up of 37.4 months and SCT censoring, the CLARA regimen was associated with a significant improvement in 2-year disease-free survival compared with HiDAC therapy (52.1% vs 30.5%; hazard ratio, 0.62; P = .042), resulting in a 38% reduction in the risk of relapse. There was a corresponding lower cumulative incidence of relapse in the CLARA arm (44.0% vs 67.7%; P = .023) with similar death in first CR/CRp (3.9 vs 1.9%; P = .60) compared with the HiDAC arm. Although the 2-year overall survival was numerically higher in the CLARA-treated cohort (68.1% vs 49.8%), it did not reach statistical significance (P = .18). In the 110 randomized patients who underwent allogeneic SCT in first remission, there were no differences in post-SCT outcome between the CLARA and HiDAC arms. In terms of tolerability, patients treated with CLARA consolidation experienced higher hematologic toxicities, more infections, and more liver toxicities compared with those treated with the HiDAC regimen. Based on these results, the study authors concluded that clofarabine-based consolidation therapy might be a reasonable postremission therapy in younger patients with intermediate- and unfavorable-risk AML in first remission, particularly in those who are not eligible for allogeneic SCT.
- Thomas X, et al. ASH 2015. Abstract 218.