Salvage Chemotherapy Regimens for Acute Myeloid Leukemia: Is One Better?.

The vast majority of acute myeloid leukemia (AML) patients will relapse after initial therapy. Allogeneic hematopoietic cell transplant (AHCT) remains the only curative option in relapsed or refractory (RR)-AML. Currently, there is no standard or preferred regimen in the salvage setting. Regimens combining cladribine, high dose cytarabine and G-CSF (CLAG), or etoposide, cytarabine and mitoxantrone (MEC) in RR-AML yield complete remission (CR) rates of 50% and 66%, respectively (Wrzesieñ-Kuœ 2003, Amadori 1991). We hereby compare the efficacy of treatment with the CLAG and MEC regimens in RR-AML.

A retrospective non-randomized comparison was performed for RR-AML patients who received CLAG or MEC regimens. The CLAG regimen consisted of: cladribine 5mg/m²/day IV on days 2-6, cytarabine 2gm/m²/day IV days 2-6 and filgrastim 300mcg daily on days 1-6. The MEC regimen included mitoxantrone 8mg/m²/day IV on days 1-5, etoposide 100mg/m²/day IV on days 1-5, cytarabine 1gm/m²/day IV on days 1-5. Data collected included baseline demographics and disease characteristics such as AML subtype, cytogenetics, duration of remission, prior therapies, response rates and overall survival (OS). The primary objective was to compare CR rates between the two regimens; the secondary endpoint was OS. International Working Group criteria were used to define CR. Primary refractory AML (PR-AML) in this study was defined as failure to achieve CR1 and less than 50% reduction in myeloblasts after first line of induction. All analyses were conducted using SPSS version 15.0. (SPSS Inc, Chicago, IL). The Kaplan–Meier method was used to estimate median overall survival; chi-square test was used for comparison of categorical variables and t-test for continuous variables. Log rank test was used to compare Kaplan–Meier survival estimates between two groups.

Between January 2005 and June 2008, 162 patients were treated with CLAG or MEC for RR-AML. Patient baseline characteristics were similar between the two groups with respect to age, sex, FAB subtype, antecedent hematological disease history, cytogenetics, and prior therapy. The regimens were used as salvage for either PR- AML, or relapsed disease. Overall CR rates were CLAG, 38% (35/87) and MEC, 24% (15/63) (p= 0.048). The OS was 7.3 months for CLAG and 4.47 months for MEC, p=0.047. The mean length of stay was 31.2 vs. 32.5 days (range 2-107 days) respectively. For patients who received those regimens for PR-AML (n=55). No difference in the mean myeloblasts% at diagnosis or at time of reinduction was observed between the two regimens. CR rates were 45.5% (15/33) for CLAG and 22.2% (4/18) for MEC, p= 0.09. More patients treated with MEC (55.6%) had residual disease after treatment compared to CLAG (21.2%), (p=0.03). The median OS for the PR-AML patients who received CLAG was 10.97 months vs. 4.47 months for MEC (p=0.068). For Patients who were treated at time of first relapse (n=70), CR rates were CLAG, 36.8% (14/42) and MEC, 25.9% (7/28) (p=0.354). The OS in first relapse was similar between the two arms: CLAG 6.7 months and MEC 6.73 months (p=0.87). Among RR-AML patients ≤ 65 years, 36% of patients who received CLAG proceeded to AHCT compared to 25% with MEC.

In this retrospective analysis, the CLAG regimen yielded significantly higher CR rates compared to MEC in RR-AML. There was a trend for improved OS particularly in the primary refractory setting, where CLAG regimen showed an additional OS benefit of 6.5 months. The higher CR rates and superior DFS and OS are clinically significant, supporting the use of CLAG as a preferred regimen for RR-AML patients.

Off Label Use: CLAG and MEC regimens for AML.