How to Choose Between Intensive and Non-Intensive Chemotherapy in Older AML Patients

Key Takeaways:

• Choosing between intensive and nonintensive chemotherapy is not a clear-cut decision for older patients with acute myeloid leukemia (AML)

• The recently developed AML composite model provides a new way to assess risk prior to choosing a treatment strategy

• Treatment decisions should be based on a combination of objective and subjective criteria

This transcript has been edited for clarity.

So the answer to the question—intensive versus nonintensive treatment, how to choose—is not clear, and we cannot uniformly answer this question. Until now, the criteria by which unfitness is defined are based on retrospective studies meant to identify variables that predict a poor outcome following intensive chemotherapy, such as low response rate, high early mortality, or poor overall survival. 

But there are important limitations of the proposed definition criteria for unfitness. First, the criteria are derived from analysis of intensively treated patient populations. And secondly, performance score and certain comorbidities may be confounded with potentially reversible leukemia-related complications, like anemia, infection, hyperleukocytosis, and so on. 

And thirdly, there is insufficient awareness of the multiple dimensions of frailty in older patients. These include physical function, polypharmacy, cognition, social support, and nutritional status. A comprehensive geriatric evaluation of all the AML patients revealed that [about] 30% had significant cognitive impairment. And a short physical performance battery score was able to identify patients at high risk of early mortality among patients with a good performance status of 0 to 1.^[1] Factors independently associated with poor outcome are age [over] 65 years, performance status above 2, Hematopoietic (Stem) Cell Transplantation Comorbidity Index, the HCT-CI index, over 3, or high white blood cell count and unfavorable cytogenetics.^[2] 

Recently, Sorror and coinvestigators proposed a new scoring system—the AML composite model.^[3] Comorbidities, including those already incorporated in the HCT-CI, were evaluated. The addition of parameters like hypoalbuminemia, thrombocytopenia, a high level of LDH, were of additive value. And this AML composite model allowed for patients between 65 to 75 years, the identification of three risk groups, with 1 year's overall survival of 86%, 50%, and 23%, respectively.^[3] You could imagine that the first group with the 1-year survival of 86% would benefit from an intensive approach, while the third certainly would not benefit from intensive treatment. 

As reflected by several recommendations for AML management in elderly patients, age, performance status, comorbidities, and disease features, as well as patient wishes, and physical appraisals, are major determinants in the decision-making process in multivariate analysis.^[4,5] In the large study that I mentioned before—that was the one by Sorror—20% of all patients received low-intensity treatment. But this varied from 4% to 33% among five participating centers. And this variability was not explained by differences in patient characteristics, further illustrating the subjectivity in treatment choice even between highly specialized centers.^[3] 

Some may argue that an experienced physician's assessment may be as good as an imperfect scoring system. But it is important to base treatment decisions on objective criteria and utilize stratification systems, such as the one proposed by Sorror.^[3] Or more simpler systems, like the one proposed by the Italian GIMEMA group, which uses the consensus-based process to define unfitness according to the following criteria: age over 75 years, poor performance status, and severe cardiac, pulmonary, renal, or other comorbidities. And this scoring system is often referred to as the Ferrara criteria.^[6] So the decision to treat intensively or not should be based on objective—but is also based on subjective—factors, including the wish of the patient.