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Editorials
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Figure 1. Mechanisms of action of hypomethylating agents, and overall survival of Swedish patients 70 years and older by treatment. (A) Mechanism of action for treatment with hypomethylating agents (HMA). DNA methyl transferases (DNMT). (B) Overall survival (OS) according to therapy. Acute promyelocytic leukemia is excluded (non-APL). All patients 70 years and older. HMA versus intensive treatment; P=0.056. (C) de novo acute myeloid leukemia (AML). HMA versus intensive treatment; P=0.028. (D) AML secondary to previous myelodysplastic syndromes (MDS), myeloproliferative neoplasia (MPN) or chemo-radiotherapy (secAML). HMA versus intensive treatment; P=0.33.
monotherapy in the near future.
Intensive AML treatment is toxic and requires massive
supportive care and long-term hospitalization. Older patients with comorbidity may not tolerate this, even though half of the selected older patients achieve com- plete remission from intensive treatment,5 and mostly so within one month. Response to HMA is less frequent and often takes much longer to achieve, but is usually well manageable in the outpatient department. The role of intensive consolidation and maintenance has still not been determined, and HMA may serve as maintenance also after intensive chemotherapy.23 Importantly, subsets of AML respond well to intensive treatment, whereas patients with secondary AML and/or complex or MDS- like genetics do poorly with chemotherapy5,7 (Figure 1), and such patients are better off with HMA. Responding patients may be eligible for alloSCT as a curative
approach, whether response was achieved from intensive treatment or from HMA.
Clinical and academic studies always introduce patient selection, and the interpretation of retrospective non-ran- domized trials should include consideration of potential differences in the actual management of different patient subsets. This problem can be overcome in part by assess- ing patients' characteristics, prognostic factors and propensity score matching. The Talati et al. study includes a large number of patients diagnosed since 1995, i.e. some of them were treated as part of the early development of HMA.8 However, results were similar when comparing outcome for patients diagnosed before and after 2005. What is striking is that half the Moffitt Cancer Center patients had prior MDS (some also had prior HMA treat- ment), as compared to 18% in the AML-001 study,18 25% in the Austrian registry study,20 12% in the Danish popu-
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haematologica | 2020; 105(2)