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Clofarabine in pediatric AML
27% in 11 patients with refractory 1st relapse; and 50% in 8 patients with ≥2nd relapse (Table 4). Of the 18 patients pre-treated with FLA-DNX (refractory 1st relapse, n=11; second relapse n=7), 6 patients (5 CR/1 CRi) responded (33%). Three responders (1 CR/2 CRi) were seen in the group of refractory 1st relapse patients. In the expansion cohort at DL4 (n=10), the overall response rate was 80% (2 CR, 5 Cri, 1 PR) (Online Supplementary Table S4). In 9 of the 18 patients with FAB M4 and M5 AML an objective response was seen; this was equally divided between both groups (FAB M4 and M5). Of the 13 patients with other FAB classifications, 9 objective responses were seen (69%, P M4/M5 vs. other FAB 0.284).
Following clofarabine, 22 patients underwent SCT (17 MUD, 1 matched family donor, 1 HLA identical sibling and 2 haplo-identical, 1 unknown). Of the 21 clofarabine
responding patients, 18 subsequently underwent SCT. Overall, 9 of the 22 patients who were transplanted died (6 MUD, 1 matched family donor, 1 haplo-identical, 1 unknown); this included 2 patients with SCT-procedure- related deaths and one death due to lung toxicity with CMV reactivation. The remaining patients died due to progressive leukemia. At time of database lock, 10 of 34 patients were alive with a median survival time of 56 months (range 32.3-78.4 months). The 1-year pEFS was 35.3±8.2% and the pOS 50.0±8.6% (Figure 2A and B); the 2-year pEFS was 26.5±7.6% and the 2-year pOS 32.4±8.0%. The 1-year pEFS was 57.1±10.8% in the 21 responding patients, and the pOS was 71.4±9.9%; the 2- year pEFS was 42.9±10.8% and the pOS 47.6±10.9% (data not shown). Most events in the 21 responders were due to relapse (Figure 2C). In the 10 patients treated at the
AB
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Figure 2. Survival estimates after clofarabine combination chemotherapy reinduc- tion. (A) Overall survival of all patients. (B) Event-free survival of all patients. (C) Cumulative Incidence of relapse of the 21 responding patients. (D) Overall survival of all patients at dose level (DL) 4. (E) Event-free survival of all patients at DL4. N: number; F: females; F: failure (event).
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