Commentary

Improving survival in older AML patients


 

The prognosis of AML in the elderly is very poor, with 5-year survival rates less than 10% in patients aged 65 years and older. However, in recent years, novel therapeutic approaches have been developed to focus on the older AML population. Have we begun to witness an improvement in the survival of these patients?

Dr. Jeffrey Lancet is chair of the department of malignant hematology at H. Lee Moffitt Cancer Center in Tampa.

Dr. Jeffrey E. Lancet

A key question to ask at the outset of any discussion pertaining to improving survival in older patients with AML is how poorly do patients fare with no disease-specific therapy at all? This is important because it speaks to the issue of treatment itself (of any type) being important in the achievement of a survival benefit.

Several clinical trials and observational registration studies have made it very clear that, without treatment, the survival in AML is very short – ranging from 11-16 weeks (for patients enrolled in therapeutic trials who received best supportive care only) to only 6-8 weeks in the “real-world” setting, based upon observational studies.1,2,3,4

These data are very meaningful because older AML patients often do not receive active therapy. As recently as 2009, SEER data indicate that 50% of patients aged 65 years or older receive no treatment for AML. This trend appears to be changing, based upon data from the AMLSG in 2012-2014, in which only a minority of patients in this age range received best supportive care only for their AML.

Knowing the very poor outcomes of patients who are not treated for AML, along with a high number of patients who are not treated, we must next ask whether any treatment at all is superior to no treatment. The data appear relatively clear on this question, with two representative publications highlighting the superiority of treatment vs. no treatment. First, in the SEER registry analysis by Medeiros et al., treated patients had a median survival of 5 months, compared with 2.5 months in untreated patients, and there was an unequivocal survival advantage attributed to treatment after adjustment for covariates and propensity score matching. Treatment included both traditional induction regimens and hypomethylating agent (HMA) therapy. Similarly, a phase 3 clinical trial testing low-dose cytarabine (LDAC) vs. best supportive care demonstrated survival improvement with LDAC (odds ratio, 0.60).

Recognizing that treatment improves survival in older adults with AML and that there is an upward trend in the percent of patients who receive active therapy, we can reasonably ask next whether survival has begun to trend upward over the past several years. This, of course, is a challenging question, but one that can be at least partially addressed through analyses of registration cohorts.

SEER data regarding AML patients aged 65 and older from the 1970s to 2013 suggest modestly improved 2-year survival, from less than 10% in the 1970s to 10%-15% since the early 2000s. The Moffitt Cancer Center database of patients aged 70 years and older also indicates a strong trend toward modestly improved survival after 2005, compared with prior to 2005 (unpublished data). Although the precise reason for trending improvements in overall survival of these patients over time is not clear, it is reasonable to suggest that a greater proportion of patients who receive actual therapy for AML could explain the modest improvements being observed. Improvements in supportive care through the years could also contribute to survival improvement trends over time, though this hypothesis has not been formally tested.

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