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.

Post-remission measurable residual disease directs treatment choice and improves outcomes for patients with intermediate-risk acute myeloid leukemia in CR1

“…Induction chemotherapy was performed for two cycles if the patients achieved CR or partial remission (PR) in the first cycle. Otherwise, those who had no-remission (NR) after the first cycle received FLAG (30 mg/m 2 fludarabine on days 1–5, 2 g/m 2 Ara-C on days 1–5, and 300 µg G-CSF on days 0–5) or CLAG (5 mg/m 2 cladribine on days 1–5, 2 g/m 2 Ara-C on days 1–5, and 300 µg G-CSF on days 0–5 [ 17 , 18 ]. After two cycles of induction chemotherapy, patients who were NR were administered decitabine + CAG (cytarabine, aclarubicin, and G‐CSF) or were enrolled in a clinical trial, and the CR/complete remission with incomplete count recovery (CRi) patients were given consolidation chemotherapy, which consisted of one cycle of IDAC (i.e., intermediate-dose cytarabine, 2 g/m 2 q12h for 3 days).…”

Exploring the Metabolic Landscape of AML: From Haematopoietic Stem Cells to Myeloblasts and Leukaemic Stem Cells

“…L-asparaginase converts asparagine to aspartic acid and has shown potent anti-leukaemic activity and has been used for the treatment of patients with de novo and relapsed AML ( 125 , 126 ). The combination of L-asparaginase with high-dose Ara-C and mitoxantrone has resulted in positive outcomes in AML patients with an aberrant asparagine metabolism ( 125 , 150 ). These results have led to the initiation of a randomised phase 2b trial which evaluates the efficacy of ERY001, L-asparaginase encapsulated in red blood cells, in elderly AML patients who are unfit for intensive chemotherapy ( 127 ).…”

Efficacy and toxicity of CLAG combined with pegylated liposomal doxorubicin in the treatment of refractory or relapsed acute myeloid leukemia

“…Nevertheless, improvements in HSCT are urgently needed; for example, the optimal timing, conditioning regimen, and donor choice (when there is more than one available donor) need to be identified. 8,9 The overall toxic side effects of CLAG+PLD were not significantly greater than those of CLAG (Table 6). Patients may benefit from a tailored dose of cytarabine; specifically, in our application of CLAG+PLD, cytarabine was tailored to 1 g/m 2 , not 2 g/m 2 as in classical CLAG.…”

“…Therefore, reaching CR after either CLAG+PLD or CLAG requires prompt HSCT. Nevertheless, improvements in HSCT are urgently needed; for example, the optimal timing, conditioning regimen, and donor choice (when there is more than one available donor) need to be identified 8,9 …”