The estimated one third of patients with acute promyelocytic leukemia (APL) who are older than 60 years now enjoy a notably better prognosis than in years past, thanks to the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). However, such patients still require special management considerations, and can only benefit from treatment advantages if properly identified.
Medscape: How do the potential benefits of therapy for APL compare with other AML subtypes in older persons?
Dr. Klepin: Potential benefits of therapy are dramatically better for APL, compared with other AML subtypes. The use of non–chemotherapy based regimens with ATRA and ATO has substantially changed options for APL management. ATRA+ATO are associated with high remission and cure rates. The chance of cure with less toxicity extends the clinical benefit to adults of advanced age and, to some extent, with comorbidities.
How has the management strategy for this subgroup of patients with APL changed in recent years?
Management options have changed dramatically with the advent of non–chemotherapy-based regimens. The majority of treated older adults could be expected to achieve remissions that are durable, with less risk of major side effects during treatment. Adults with comorbid conditions, at advanced age, and with some functional limitations could also still benefit from treatment.
Does that management strategy change based on whether patients are considered low-risk or high-risk?
Clinical trials are lacking to provide best evidence for the optimal treatment for adults over age 70 years. However, based on available data and experience, the expert consensus provided in this report recommends that older adults regardless of age with low-risk disease should be offered ATRA+ATO–based therapy if available.
The optimal approach for patients with high-risk disease is less clear based on available studies. For fit older adults without cardiac disease, the use of single-drug anthracycline chemotherapy with ATRA plus/minus ATO is appropriate. However, treatment with ATRA+ATO may also provide a good response with less side-effect risk. For older patients with high-risk disease and comorbidity or poor functional status, the use of non-chemotherapy regimen ATRA+ATO is preferred.
What role does frailty have in making treatment decisions in this population?
Although frail older adults have not been specifically studied in clinical trials, it is reasonable to offer treatment with a non–chemotherapy based regimen for many of these patients, particularly if frailty may in part be related to disease burden. Frailty is a dynamic state. Rapid initiation of therapy can improve function and symptoms, potentially reversing the phenotype of frailty if driven largely by disease burden.