Background: Older adults with AML face unique treatment challenges due to age-related comorbidities, reduced tolerance to therapy, and increased frailty. In recent years, treatment strategies for elderly and less fit patients have shifted toward non-intensive induction regimens and mutation-driven targeted therapies. These treatments are commonly administered in outpatient settings, making them well-suited for use in the community oncology setting. In 2020, the FDA approved venetoclax (a BCL2 inhibitor), primarily in combination with hypomethylating agents, as induction therapy for AML patients aged 75 years and older or those unfit for intensive chemotherapy. However, real-world data on the use and outcomes of these therapies in the community setting remain limited. This study evaluates the evolving treatment patterns and outcomes in older AML patients, with a focus on non-intensive outpatient induction therapy.

Methods: This retrospective analysis examined AML patients aged ≥70 years diagnosed between January 1, 2015, and December 31, 2023, using electronic health records from The US Oncology Network and non-Network practices. Patients were grouped by age (70–74, 75–79, 80–84, ≥85). Outpatient treatment patterns, including venetoclax use, were evaluated. Kaplan-Meier time-to-event outcomes were assessed from start of first-line venetoclax-based therapy, including time to discontinuation (TTD), time to next treatment (TTNT), and overall survival (OS), and were compared across age groups using the log-rank test. With a data cutoff of June 30, 2025, the dataset covered 4.5 years post-venetoclax approval.

Results: A total of 1,093 patients were included: 30.7% (n=336) 70–74, 32.3% (n=353) 75–79, 22.5% (n=246) 80–84, and 14.5% (n=158) ≥85. Sex distribution was consistent across age groups (~60% male; ~40% female). Race distribution was 86.7% White, 6.4% Black, and 6.9% other races. High use of outpatient regimens—especially venetoclax with hypomethylating agents (81.2%)—were observed among patients aged 70–80 following its 2020 approval The median (95% confidence interval [CI]) OS was 11.0 (10.2 -12.0) months, with significant differences by age at diagnosis (log-rank p=0.003). Two-year OS rates were 26.9% overall, and ranged from 31.2% (75–79) to 18.3% (≥85). Four-year OS rates declined with age, from 13.2% (70-74) to 4.9% (≥85). TTNT events were observed in the majority of patients (79.2%, n=866), with similar median (95% CI) durations across age groups (7.6 [6.8 -8.5] months overall and log-rank p-value=0.07). A similar trend was found in TTD, with median (95% CI) durations of 5.2 (4.7 – 5.5), 5.5 (4.7 – 6.6), 4.8 (3.2 – 6.2), 4.5 (2.7 – 5.8) months for the 4 age groups, respectively (log-rank p-value=0.25).

Conclusions: This real-world analysis of older AML patients showed high adoption of non-intensive induction with venetoclax based regimens in the US community oncology setting. To our knowledge, this is the largest real-world analysis of contemporary treatment of older AML patients. Comparable TTNT and TTD across age groups suggest that even very old patients can sustain similar treatment durations. As expected, OS declined with increasing age; however, the overall median OS of 11.0 months approaches outcomes observed in the VIALE-A trial of azacitidine and venetoclax induction (14.7 months), with similar trends in 2- and 4-year survival rates. Continued research, including integration of important unstructured variables such as genetic risk profiles, dose and modifications, rate and duration of remissions, stem cell transplants, and adverse events, is essential to better characterize this treatment in the elderly AML population. As targeted therapies continue to be adopted and personalized outpatient management grows, real-world data will remain essential to inform the evolving treatment landscape to improve the quality of life and survival of these patients.

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2025
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