Comparison of High-Dose Cytarabine, Mitoxantrone, and Pegaspargase (HAM-pegA) to High-Dose Cytarabine, Mitoxantrone, Cladribine, and Filgrastim (CLAG-M) as First-Line Salvage Cytotoxic Chemotherapy for Relapsed/Refractory Acute Myeloid Leukemia

Abstract

Currently, no standard of care exists for the treatment of relapsed or refractory acute myeloid leukemia (AML). We present our institutional experience with using either CLAG-M or HAM-pegA, a novel regimen that includes pegaspargase. This is a retrospective comparison of 34 patients receiving CLAG-M and 10 receiving HAM-pegA as first salvage cytotoxic chemotherapy in the relapsed or refractory setting. Composite complete response rates were 47.1% for CLAG-M and 90% for HAM-pegA (p = 0.027). Event-free survival was significantly different in favor of HAM-pegA (p = 0.045), though overall survival was similar between groups. There were no significant differences in toxicities experienced by patients treated with the two regimens, including adverse events of special interest related to pegaspargase (venous thromboembolism, hemorrhage, hepatotoxicity, pancreatitis, and hypersensitivity reactions). HAM-pegA is a novel regimen for relapsed or refractory AML that resulted in improved response rates and similar toxicities compared to CLAG-M.

Keywords: CLAG-M; HAM-pegA; acute myeloid leukemia; asparaginase; refractory; relapsed.

Conflict of interest statement

V.H.D. reports serving on an advisory board for Pfizer. A.E. has received research grants from Jazz Pharmaceuticals and NewLink Genetics, is a global oncology advisory board member for Amgen, has served as an advisory board member for Genentech and Servier, and is a Co-Founder and Scientific Advisor for KinaRx, LLC. A.P.D. reports serving on the speakers’ bureau for Amgen and on an advisory board for Astellas Pharma US, Inc.

Figures

Figure 1

(a) Overall survival, with the solid line representing CLAG-M and dashed line representing HAM-pegA (p = 0.135) (b) Event-free survival, defined as time to relapse or death, with the solid line representing CLAG-M and dashed line representing HAM-pegA (p = 0.045).

Figure 2

Incidence of grade 3/4 Adverse Events in 30 days. No adverse event was statistically different between the two groups. There was an absence of the following grade 3/4 adverse events in both groups: venous thromboembolism, alkaline phosphatase elevation, hepatic failure, amylase/lipase elevations, pancreatitis, and hypersensitivity reactions.