P525: long-term outcomes of stem cell transplant in older patients with acute myeloid leukemia treated with venetoclax + hma therapies

Background: Allogeneic hematopoietic stem cell transplantation (SCT) remains the most effective curative treatment for patients with intermediate- and poor-risk acute myeloid leukemia (AML); however, patients who are ineligible to receive intensive chemotherapy (IC) due to age or comorbidities have typically not been viable candidates. Venetoclax (Ven) in combination with hypomethylating agents (HMAs) leads to rapid and durable remissions in newly diagnosed patients with AML who are ineligible for IC. Aims: To evaluate the long-term clinical outcomes of SCT after Ven+HMA treatment in the aforementioned patient population. Methods: Patients with newly diagnosed AML ineligible for IC who received Ven+HMA and proceeded to SCT on the phase 1b, open-label (NCT02203773) trial of Ven plus decitabine (Dec) or azacitidine (Aza) and the phase 3 VIALE-A trial (NCT02993523) of placebo + Aza vs Ven+Aza were included. Patients in the phase 1b trial received Ven daily (400, 800, or 1200 mg) with either 20 mg/m2 intravenous (IV) Dec on days 1-5 or 75 mg/m2 subcutaneous (SC) or IV Aza on days 1-7 of 28-day cycles. Patients in VIALE-A received Ven daily (400 mg) with 75 mg/m2 SC or IV Aza on days 1-7 of 28-day cycles. Patients were evaluated for efficacy outcomes before and after SCT that included best response (complete remission [CR] or CR with incomplete hematologic recovery [CRi] or CR with partial hematologic recovery, morphologic leukemia-free state [MLFS]), time to best response, measurable residual disease (MRD) negativity before SCT, 2-year post-SCT remission and 2-year post-SCT overall survival (OS). Results: A total of 33 patients were included in this analysis (31 from the phase 1b trial and 2 treated with Ven+Aza from VIALE-A). Patients had a median age of 69 years, 70% had de novo AML, and 60% had adverse risk disease based on 2022 ELN categories (Table). Mutations were observed at baseline in FLT3 in 5/20 patients (25%), NPM1 in 5/18 patients (28%), IDH1/2 in 7/20 patients (35%), and TP53 in 2/18 patients (11%). The median time on Ven before SCT was 4.18 months (range, 0.9-31.8), and the median time from last dose of Ven+HMA to SCT was 1.22 months (range, 0.4-10.3). Before SCT, 27 patients (82%) achieved a best response of CR/CRi, 3 achieved MLFS, and 3 had resistant disease. Median time to CR/CRi was 1.9 mo (range, 0.8-7.1), and 9 patients (27%) had an MRD response of <10-3. Median OS after SCT was 29.9 mo (95% CI, 15.8-NR), with a 69% 12-mo post-SCT OS rate. In patients who had MRD responses before SCT, the 12-mo post-SCT OS rate was 76%. In 18 patients with adverse ELN risk disease, median OS was 15.8 mo (95% CI, 4.5-29.9), and the 12-mo post-SCT survival rate was 56%. Of the 2 patients who had TP53 mutations, 1 died within 12 mo of SCT, and the other was alive 24 mo following SCT. Summary/Conclusion: Ven in combination with Aza or Dec can lead to rapid and deep responses in patients with newly diagnosed AML who were ineligible for IC. Most patients were alive ≥12 mo after SCT, including approximately half of those with adverse ELN risk disease. These results suggest that Ven+HMA can enable receiving curative SCT and long-term disease-free states in patients who are ineligible for IC.Keywords: Acute myeloid leukemia, Venetoclax, Stem cell transplant