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Editorials
lation-based study including all ages,6 and 28% of patients aged ≥70 years given AML-specific treatment according to the Swedish AML Registry.4,5 Still, the Talati et al. study had the best reported median survival with HMA and is the only study so far to show better survival with HMA than with intensive treatment (Table 1).8
The therapeutic options for AML in older people are now rapidly expanding, including oral targeted drugs with low toxicity, such as kinase inhibitors with activity in AML with FLT3-mutations, oral inhibitors of IDH- mutations, and many more.1 These drugs have been shown to be active as monotherapy, and some are already approved by the FDA. However, both theory and practice indicate synergistic effects of combining drugs with dif- ferent modes of action. Clinical studies are, therefore, rapidly moving towards regimes with HMA used as back- bone therapy, comparing monotherapy with add-on of further drugs, of which there are several. Expectations are high from the combination of HMA with the BCL2- inhibitor venetoclax, that has resulted in very high com- plete remission (CR) rates (67% CR + CR with incom- plete blood count recovery) and a median overall survival of 17.5 months when used as primary treatment of older AML patients (median 74 years),24 although real-world response rates were somewhat lower.25 (The outcome of the phase III study with Aza + venetoclax/placebo may be presented in 2020.) Furthermore, an oral analog of Aza (CC-486) has recently been reported to be effective to maintain remission from AML.26 We thus expect numer- ous studies evaluating HMA-based new combinations, and all-oral limited-toxicity treatments are within sight.
In summary, traditional combination chemotherapy with or without the addition of targeted therapies is like- ly to keep its role for years to come for many patients without severe comorbidity up to the age of around 75 years. However, patients with secondary AML and/or high-risk genetics should now already be offered less toxic HMA-based therapies, preferably as part of one of the many ongoing clinical trials, in order to expand our clinical armamentarium as quickly as possible.
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