Comparison of Mitoxantrone-Based Salvage Therapies (MEC vs CLAG-M) in Relapsed or Refractory Acute Myeloid Leukemia

Introduction:

Primary refractory and early relapsed acute myeloid leukemia (RR-AML) continue to pose a therapeutic challenge. There are currently a number of treatment strategies for RR-AML, with performance status, cytogenetics, and availability of appropriately matched allogenic hematopoietic cell transplant (HCT) donors all influencing that clinical decision. Salvage therapy treatment regimens for refractory and relapsed disease are not standardized but include mitoxantrone, etoposide, and cytarabine (MEC) and cladribine, cytarabine, filgrastim, and mitoxantrone (CLAG-M), among many others. While previous studies have established the roles of MEC, and CLAG-M independently and have retrospectively compared MEC vs CLAG; no retrospective analysis of MEC vs CLAG-M has been published to date, though both remain commonly used regimens in practice. In this retrospective single-center analysis we compare the outcomes of patients receiving MEC or CLAG-M as salvage therapy for RR-AML.

Methods:

The study included 55 patients with RR-AML who received MEC or CLAG-M between 09/01/2009 and 12/31/2016. Information about sociodemographics, disease and transplant characteristics and clinical outcomes were obtained by medical record review. The probabilities of overall survival (OS) and relapse-free survival (RFS) were estimated according to the Kaplan Meier method and log-rank test was used to compare outcomes between patients who received either of the two regimens.

Results:

Fifty five consecutively treated patients with RR-AML were included in this analysis, 44 patients received MEC and 11 patients received CLAG-M. The median age of patient was 58.5 years (18-75) among MEC recipients and 54 years (23-64) in the CLAG-M group, with 53% being males. The majority of patients had relapsed disease (n=38, 69%). High risk subtypes of AML, as determined by cytogenetics and molecular studies, predominated with 87% (48/55) being high risk.

Cytoreduction was achieved in 30 (68%) of patients who received MEC, and 8 (73%) patients who received CLAG-M achieved cytoreduction. HCT was pursued in 33 (75%) of patients who received MEC and 9 (82%) who received CLAG-M. Median follow-up after transplant was 30 months from treatment with either MEC or CLAG-M (5 - 60 months), 17 (52%) and 3 (27%) were alive from the MEC and CLAG-M groups respectively. In the follow-up interval for transplanted patients, 9 (27%) from the MEC group and 6 (55%) from the CLAG-M group relapsed, with a median time to relapse from the date of transplant of 9.1 months (0.4 -30 months) and 2.9 months (1.8 - 11 months), respectively.

Median time to relapse for patients who received HCT was 12 months (0-76 months) for the MEC group and 5.5 months (2-35 months) for the CLAG-M group. Relapse free survival at 24 months between the MEC and CLAG-M treatment groups that went to HCT were 67% (51-87%) and 11% (1.8-71%), respectively with an associated hazard ratio (HR) of 3.86 (1.55-9.59, CI 95%, p 0.0016). Similarly, overall survival analysis at 24 months was 66% and 11% for MEC and CLAG-M respectively, with a HR of 3.85 (1.51 - 9.81, 95% CI, p=0.002).

Discussion:

While induction therapies for AML are fairly standard, there are numerous potential salvage therapies that serve to bridge a person to transplant in RR-AML. With allowances that a degree of agent availability and provider familiarity with treatment likely biases the selection of one regimen over another, our results would suggest a treatment benefit both in terms of RFS and OS in patients with RR-AML who receive MEC over CLAG-M and ultimately go to HCT.

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