The Effect of Comorbidities and Choice of Treatment on Overall Survival in Elderly Patients with Acute Myeloid Leukemia: A Beaumont Experience

CONTEXT: First line therapy for acute myeloid leukemia (AML) is the 7+3 regimen, consisting of cytarabine and an anthracycline. Due to its high intensity, it often cannot be used in elderly patients. Venetoclax in combination with a hypomethylating agent (HMA) is approved for AML treatment in these patients who will likely be unable to tolerate the traditional 7+3 regimen. In our study, we investigate the efficacy of venetoclax + HMA in a community setting.

OBJECTIVE: The primary outcome of our study was overall survival of patients greater than 65 years of age with a diagnosis of AML who received 7+3 therapy versus those who received venetoclax + HMA. Secondary outcomes included median survival time in each group, as well as characteristics of those who received 7+3 versus venetoclax + HMA therapy.

DESIGN: A retrospective chart review was conducted using the Electronic Medical Record at the Royal Oak and Troy locations of Beaumont Health which are community based tertiary referral centers. Inclusion criteria included patients seen by the Beaumont Hematology and Oncology Group that were 65 years of age or older with a diagnosis of AML by bone marrow biopsy who received treatment for AML. Patients were seen between September 01, 2019 and September 01, 2022. Data collection was completed February 1, 2022.

INTERVENTION: Standard dosing of cytarabine and daunorubicin were used in the 7+3 regimen. Standard dosing of venetoclax plus an HMA (azacitidine or decitabine) were used. Dose adjustments were made according to physician discretion.

RESULTS: Overall survival of those receiving 7+3 was significantly higher than those who received venetoclax + HMA as initial treatment (p=0.0403). Of the 23 patients who received 7+3 as their initial treatment, 13 passed away with a median time of death of 1.98 years. The median time of death of the 17 of 26 patients who passed away in the HMA + venetoclax regimen was 0.71 years (p=0.039). The initial treatment of HMA + venetoclax was associated with 2.19-fold greater hazard of mortality as compared to 7+3 (HR:2.19; P = 0.0403). Patients that received initial treatment of 7+3 had less comorbid conditions (4.5 versus 6.1; p=0.04) and were younger (60 versus 75.5; p<0.0001) than those that did not receive the initial treatment of 7+3.

CONCLUSION: Median survival for those who received HMA + venetoclax was less than those who received 7+3, likely due to the selection bias of older age and higher comorbdities in those who received HMA + venetoclax versus those who received the 7+3 regimen. Our hospital appears to be using the HMA + venetoclax regimen in appropriate patients; those who were older or had a higher number of comorbidities. HMA + venetoclax still appears to be a good alternative for those who cannot tolerate the first line 7+3 chemotherapy regimen for acute myeloid leukemia, and further studies comparing it to elderly patients with AML who choose not to undergo treatment would be helpful.

No relevant conflicts of interest to declare.