Introduction: Patients with AML are suffering from low cell counts resulting in higher risks for infections and bleeding. Patients aged above 65 years are often treated with palliative therapy due to comorbidities. Treatment with hypomethylating agents (HMA) as single agents or in combination with Venetoclax is a standard therapy for patients who are ineligible for allogeneic stem cell transplantation.

Methods: Clinical data of 560 AML-patients who were treated at our department were retrieved from the Düsseldorf Registry and followed up until May 31st 2025. Overall survival was assessed using Kaplan-Meier method. Unfitness of patients regarding induction or allografting was determinated by the treating physicians.

Results: Median age at treatment initiation was 74 years (range 65 - 93). 330 patients were male (59%). 483 patients (86%) died within the observation period. 126 patients received best supportive care only (22.5%) (group A), 189 patients were treated with low dose cytoreduction (33.7%) (group B), 207 patients (37%) were treated with HMA only (23% Decitabine, 77% 5-Azacytidine) (group C), and 38 patients received a hypomethylating agent in combination with Venetoclax (6.8%) (group D). ECOG > 2 was seen in 68% and 67% in group A and B, but only in 50% in group C and D. ELN risk group was known in 297 cases, 5% belonging to the low risk group, 56% to the intermediate risk group, and 39% to the high risk group. Neither median age of the groups nor the hemoglobin values (8.9 g/dl), number of absolute neutrophils (1500/µl) or platelet counts (59.000/µl) did differ significantly. WBC was higher in group B (15.000/µl) than in the other groups (p<0.005). Marrow blast percentages did not differ significantly between the groups (34%), whereas peripheral blasts were highest in group A and B (45%) versus group C and D (19% and 11%) (p<0.01). Median overall survival of the ELN low risk group was 24 months, compared to 6 months in the intermediate risk group and 4 months in the high risk group (p<0.001). Median overall survival (OS) from treatment initiation was 1 month in group A, 4 months in group B, 8 months in group C, and 18 months in group D (p=0.001). Median overall survival did not differ between patients who were treated with Decitabine (9 months) and those who were treated with 5-Azacytidine (8 months). The median duration of inpatient stay in group A was 10 days, as compared to 17 days in group B, 39 days in group C and 58 days in group D. The relative share of inpatient stay related to infections and other disease-related reasons was 80% in group A, 60% in group B, 66% in group C, and 54% in group D (p<0.05). The percentage of time as inpatient in relation to the median survival time from diagnosis was 33% in group A, 10% in group B, 16% in group C, and 11% in group D. The number of days in hospital or outpatient departments for the application of treatment of 5-Azacytidine or Decitabine was 21 (1-518) in patients of group C, and 21 days (5-77) in patients of group D who received Azacytidine or Decitabine plus Venetoclax. The percentage of days of treatment in hospital or outpatient departments in relation to the overall survival days was 12% (1-98%) in patients of group C and 7% (1-35%) in patients of group D.

Conclusion: Unfit patients aged above 65 years with AML should be offered a treatment with a hypomethylating agent whenever possible, preferably in combination with Venetoclax, as these patients have a better overall survival time compared to low dose cytoreduction or best supportive care only. There might be a selection bias associated with the ECOG performance status, that might have influence on the outcome as well. Although patients treated with HMA spend a relevant proportion of their remaining time as inpatients or in outpatient departments, partly just for the administration of the drug, their percentage amount of time spent within a hospital was lower than in BSC patients. The percentage of days in the hospital or outpatient departments in patients receiving HMA plus Venetoclax was lower compared to cytoreduction and HMA monotherapy. Oral administration of hypomethylating agents may extend the time as outpatient.

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2025
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