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V.V. Prassek et al.
chemotherapy. Consequently, we were unable to study interactions between genetic alterations and type of treat- ment (intensive versus not intensive) with regard to patients’ outcomes. However, we found that patients ran- domized to the more intensive induction regimen (HAM) tended to have longer OS compared to those randomized to TAD. While this non-significant difference may be due to the play of chance, the finding that better outcomes were observed in the more intensive arm supports the conclusion that induction chemotherapy is tolerable for selected patients in this age group. Two randomized phase III trials in newly diagnosed AML patients aged ≥65 years compared treatment with the hypomethylating agents, azacitidine and decitabine, to alternative therapies (best supportive care, low-dose cytarabine, or intensive chemotherapy).44,45 The median OS of azacitidine-treated patients was 10.4 months, and that of decitabine-treated patients was 7.7 months, compared to a median OS of 6.0 months in our study. Obviously, these cohorts of patients cannot be compared directly because of their different age ranges and inclusion criteria. While the lower age limit of our analysis was higher than that in the trials of hyp- methylating agents (75 versus 65 years), our cohort repre- sents highly selected patients who were, despite their advanced age, deemed fit enough to undergo induction chemotherapy. Notwhitstanding this obvious limitation, it is noteworthy that the 3-year OS rate in our cohort was nominally higher than the rates in both the trials of hypomethylating agents. In our study, 24 patients (21%)
were still alive 3 years after primary diagnosis, whereas two patients (1%) in the azacitidine and no patient in the decitabine trial were still alive at 3 years. Thus, at least a subset of AML patients may benefit from intensive induc- tion therapy in terms of sustained remissions and long- term survival, even at the age of 75 years or above. Nevertheless, the longer median OS achieved in the trials of hypomethylating agents suggests that these agents may be the preferred choice for many elderly patients.
In clinical practice, the choice between intensive, poten- tially curative chemotherapy or a palliative therapeutic approach in old AML patients should be guided by an evi- dence-based, individualized assessment of the potential risks (e.g., treatment-related mortality) and benefits of intensive chemotherapy. In our study, favorable- and intermediate-risk cytogenetics, IDH1-wildtype status and good performance status characterized a subset of old AML patients who may achieve long-term survival after induction chemotherapy. These patients might be candi- dates for intensive therapy in the absence of medical con- traindications. On the other hand, patients with adverse- risk cytogenetics, IDH1 mutations or poor performance status did not benefit from intensive induction therapy and might fare better with alternative strategies such as hypomethylating agents, or novel targeted agents that have recently been approved or are currently under devel- opment.46 In summary, our results show that clinicians should consider intensive chemotherapy as a therapeutic option even for selected, very old AML patients.
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