CAVEAT Trial Hints at New AML Path for Fit Seniors

To manage acute myeloid leukemia (AML) in older, fit patients, venetoclax plus a modified intensive chemotherapy regimen offers an effective, well-tolerated, time-limited approach. This was the assessment of investigators who evaluated the phase 1b CAVEAT study and published their findings in Blood Advances.

The evaluation of CAVEAT concerned a cohort of 85 patients from the trial aged 65 years and older, who had a median age of 71 years and a median follow-up of 41.8 months. For up to 14 days, these patients received induction therapy of cytarabine and idarubicin in 5 dose escalation cohorts for venetoclax of 50, 100, 200, 400, and 600 mg.

The overall response rate (ORR) calculated in the cohort was 75%, and the median overall survival (OS) was 19.3 months. Specifically in patients with de novo AML, ORR was 88% and median OS was 33.1 months.  Nearly one-third of the responding patients did not have relapse, and their median treatment-free remission was 17.9 months.

By gene mutation variants of disease, complete response rates were highest for patients who had IDH1/2 or NPM1 mutations, at 75% and 81%, respectively, and lowest for patients with TP53 mutation at 27%. The two-year OS rate was highest in patients with IDH1/2, SRSF2, or NPM1 mutation at 76%, 72%, and 69%, respectively, and lowest in patients with TP53 mutation at 13%.

Safety results of the induction therapy included a 4% prevalence of high-grade gastrointestinal toxicity and a mortality rate of 4%. Delays to hematologic recovery experienced by patients after consolidation were improved by removing idarubicin from post-remission therapy.

Reference

Chua C, et al. Blood Adv. 2025; 9(8):1827–1835. doi: https://doi.org/10.1182/bloodadvances.2024014900