Acute Myeloid Leukemia in the Elderly, Intensive or Maintenance Therapy? Our Experience in Patients Over 65 Years
Reviewer: Eric Shinohara MD, MSCI
Abramson Cancer Center of the University of Pennsylvania
Last Modified: March 23, 2007
Presenter: Mettivier, V Presenter's Affiliation: Haematology Division A.Cardarelli Hospital, Italy Type of Session: Scientific
The use of intensive chemotherapy in the treatment of acute myeloid leukemia (AML) in patients older than age > 65 years is debatable.
Numerous previous studies have suggested that intensive chemotherapy is a feasible treatment in this population of patients.
The purpose of this prospective study was to determine the difference in Event Free Survival (EFS) and Overall Survival (OS) among two groups of elderly patients with AML treated with either intensive chemotherapy (IC) or maintenance therapy (M).
Materials and Methods
54 patients with AML were accrued from June 2001 to May 2006 with a median age of 73 years (range 66-90). Thirty patients were male and twenty four were female.
Twenty seven patients were treated with IC with Fludarabine, Ara-C, and G-CSF (Flag) and mitoxantrone, cytarabine and etoposide (MICE). The median age of these patients was 71 years. Sixteen were male and eleven were female.
Twenty seven patients were treated with maintenance therapy with low dose cytarabine and/or supportive care. The median age of these patients was 78.5 years and fourteen were male and thirteen were female.
Twelve patients (45%) in the IC group had a complete remission (CR) in response to treatment and had median EFS and OS of 4.47 and 7.15 months respectively. The rate of transplant related mortality ( TRM) was 25%. In the group of patients who received M 30% (eight patients) had a CR and the median EFS and OS of 4.22 and 4.94 months respectively.
The CR rates were highest in the IC group. These results demonstrated a trend towards significantly improved OS (p= 0.7) between the IC and M groups.
In conclusion IC did not improve the survival of elderly patients with AML.
New therapeutics strategies are necessary to improve the EFS and OS in these patients.
This study addressed the efficacy of IC regiments in patients older than 65 years of age. The authors draw the conclusion that IC does not improve OS and therefore should not be used in the older population at present.
There are several concerns about the validity of this conclusion. In the present study it is not clear if there was randomization of patients between the treatment arms and therefore it is unclear if patients who had a higher performance status and likely a longer inherent OS were randomizing to the IC group, thus biasing the results. It appeared that there was not randomization as the ages between the two groups were fairly different, with older patients being in the M group, which could again bias results towards the IC group. This may have contributed to the increased OS seen in the IC group compared with the M group.
The high TRM likely contributed to the worse overall survival in the IC group, and determining which patients are at risk for TRM would allow the selection of more optimal patients for IC.
Recording and analysis of the difference in toxicity between the two groups would have strengthened this study to determine how well IC therapy is tolerated in the older population.
This study suggests that there is no improvement in OS with IC but randomized trials are needed to confirm this. Furthermore, newer biological agents which may be better tolerated in older patients also need to be studied.
Mar 18, 2011 - A high-dose regimen of cytarabine as induction therapy for acute myeloid leukemia offers no advantage over more conservative dosing and results in a higher incidence of toxic effects, according to research published in the March 17 issue of the New England Journal of Medicine.