Comparison of Clofarabine-Based Regimens Versus Etoposide Plus Mitoxantrone as Salvage Chemotherapy for Patients with Relapsed or Refractory Acute Myeloid Leukemia

Introduction: There is insufficient evidence regarding the optimal chemotherapy regimen for treatment of relapsed or refractory acute myeloid leukemia (RR-AML). We retrospectively compared the outcomes and toxicities between salvage chemotherapy with etoposide plus mitoxantrone (EM) versus clofarabine-based regimens in patients with RR-AML. Materials and Methods: Consecutive patients with RR-AML who received > 1 cycle of EM or a clofarabinebased regimen between March 2003 and April 2017. Results: A total of 93 patients were included in the study. Sixty-nine patients received EM and 24 patients received clofarabine-based regimens. Baseline characteristics were matched, except for a higher rate of previous EM therapy and primary refractory disease in the clofarabine arm. The overall remission rate (complete remission plus complete remission with incomplete hematologic recovery) was 36.2% in the EM arm versus 29.2% in the clofarabine arm (p = 0.62). The 3-year event-free survival (EFS) and overall survival (OS) was 17.6% and 41% in the EM arm, compared to 4.6% (p = 0.18) and 5% (p < 0.001) in the clofarabine arm. Of those treated with EM, 36.2% could undergo subsequent allogeneic hematopoietic cell transplantation (allo-HCT) versus 12.5% of those in the clofarabine arm (p = 0.04). Grade 3 or higher non-hematologic toxicities occurred in 35 (50.7%) patients in the EM arm, compared to 18 (75%) patients with a clofarabine-based regimen (p = 0.04). This is the first comparison of these two salvage chemotherapy options. Unfortunately, the imbalance with more refractory and heavily pretreated patients in the clofarabine arm limits conclusions, and more studies are necessary to validate outcomes with these regimens.