These data suggest that, in selected older adults with secondary AML who are fit enough to receive induction chemotherapy, CPX-351 offers a survival advantage, even among traditionally higher-risk subgroups, including patients with adverse karyotype of above age 70 years. As such, CPX-351 (Vyxeos) received FDA approval as frontline therapy for secondary AML in 2017.
Newer targeted therapies for older adults with AML also appear to hold promise. Glasdegib, an inhibitor of SMO (part of the hedgehog signaling pathway) was recently studied in combination with LDAC versus LDAC alone in a randomized phase 2 trial in older patients considered unfit for intensive induction chemotherapy. In this trial, patients assigned to glasdegib plus LDAC had longer median and overall survival than patients treated with LDAC alone, suggesting a promising novel agent on the horizon.9
Another example of a promising and novel targeted agent for AML is venetoclax, an inhibitor of BCL-2. Encouragingly high response rates and overall survival in phase 2 trials that combined venetoclax with LDAC or HMAs have driven randomized trials to definitively ascertain a survival advantage in older patients considered unfit for intensive therapy.10,11
The question also arises as to whether therapeutic outcomes can be optimized by better selection of currently available therapies for any given. This concept requires development of a decision analysis model that can be used to accurately predict outcomes among older patients with newly diagnosed AML. At Moffitt Cancer Center, such a model is being developed using a systematic review of the literature, followed by validation in a large institutional database. To date, there is the strong initial suggestion that initial therapy selection can be optimized for best outcome, taking into account variables including ECOG performance status, Charlson Comorbidity Index, and cytogenetic risk.12