P545: venetoclax (ven) combined with flag-ida is an effective regimen for patients (pts) with newly diagnosed (nd) and relapsed/refractory (r/r) acute myeloid leukemia (aml)

Background: Although 60% of pts with ND AML achieve complete remission (CR) with upfront intensive chemotherapy (IC), 30-40% of pts relapse underscoring the need for novel regimens capable of inducing deeper remissions via eradicating measurable residual disease (MRD). Studies have shown promising activity of VEN when combined with various IC regimens in pts with ND AML with composite CR rates (CRc) above 80% and MRD-ve rates exceeding 90% (Wang 2022; Kadia 2021). FLAG-IDA plus VEN has shown encouraging results with MRD negative (MRD-ve) CRc achieved in 93% and 71% of pts with ND and R/R AML, respectively (DiNardo 2022; Desikan 2022). Aims: The aim of this study was to investigate the clinical activity of FLAG-IDA+VEN in pts with ND or R/R AML. Methods: We conducted a single-center retrospective study to assess the clinical activity of FLAG-IDA-VEN or CLIA-VEN in pts with ND or R/R AML. VEN was administered for 7- or 14-days during induction and r7 days during consolidation, with appropriate dose adjustment of VEN for azoles. Due to recent national shortage of fludarabine, cladribine was used instead during consolidation. Molecular data was obtained using a 40-gene NGS platform. Outcomes evaluated included CR, CR with incomplete count recovery (CRi), and morphologic leukemia-free state (MLFS) using the modified International Working Group response criteria. Time-to-event analyses were estimated using Kaplan-Meier method and compared using log rank test. Results: From March 2020 to February 2023, 35 pts with AML (25 ND and 10 R/R) were included; 63% were male with a median age of 36.5 years (range, 21-68) (Table 1). In pts with ND AML, 64% had de novo AML and most pts had ELN adverse-risk disease (n = 14; 56%). The most common cytogenetic risk groups were complex (24%), diploid (24%), and KMT2A-rearranged (20%). Five pts received CLIA+VEN. Median time to initiation of therapy was 5.5 days (range, 2-14). Median number of consolidation cycles given were 2 (range, 1-5). Median time to ANC (≥ 500) and platelet (≥ 50,000) recovery were 20 days (range, 19- 42) and 20 days (range, 17- 42), respectively. Median follow-up in ND AML pts was 5.4 months (mths; range, 1-16.7). Nineteen pts (76%) achieved CR/CRi. MRD status was available for 8 pts; 6 pts achieved MRD negativity using flow cytometry (<10-3). Of the 19 responders (ELN favorable, N=4; Intermediate, N=7; Adverse, N=8), 15 pts remain alive in CR/CRi for a median of 6.7 mths (range, 1.2-15.8), of which 8 pts received allo-SCT. Four pts with adverse risk disease relapsed and died due to AML 0.2, 4.7, 5.5, and 8.2 mths after relapse, respectively. Six pts with adverse risk AML (24%) did not respond to therapy and died due to disease progression (PD). Ten pts with R/R AML were included; 9 were in salvage 1 and 1 pt received prior allo-SCT. All pts responded: 8 CR/CRi and 2 MLFS. Of the 8 pts who achieved CR/CRi, 6 were bridged to allo-SCT (2 of which relapsed 2 mths after allo-SCT and died due to PD), 1 pt died in CR due to sepsis after 3 cycles of consolidation, and 1 remains alive in CR for 5+ mths. The 2 pts who achieved MLFS died due to PD and fungal pneumonia after 5.3 and 1.5 mths from start of therapy, respectively. Five pts remain alive in CR/CRi for a median of 4 mths (range, 1.5-17.7). Median OS for pts with ND and R/R AML were 16.5 mths (95% CI: 0.7-6) and 8 mths (95% CI: 0.2-1.4), respectively (p=0.64; Figure 1). Among ND AML, median OS was significantly longer for responders compared to non-responders (16.5 mths vs 2.7 mths; p= <0.0001). Summary/Conclusion: FLAG-IDA+VEN is an effective regimen in AML. Larger multicenter studies and longer follow up are needed to confirm the efficacy and safety of this combination.Keywords: Relapsed acute myeloid leukemia, Acute myeloid leukemia, Venetoclax, Fludarabine