Purine-Analog Based Intensive Chemotherapy (IC) Combined with Venetoclax (VEN) Is Highly Active in Newly Diagnosed (ND) and Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.2887-2887
• Main Authors: Lachowiez, Curtis A, Cohen-Nowak, Adam Julian, Khan, Talha, Cwykiel, Joanna, Tabiti, Bukky Florence, Khan, Irum, Dinner, Shira N., Grenet, Justin, Agha, Aya, Saultz, Jennifer N., Gandhi, Arpita, Meyers, Gabrielle, Newell, Laura F., Leonard, Jessica T., Hayes-Lattin, Brandon, Traer, Elie, Maziarz, Richard T., Cook, Rachel J., Swords, Ronan T., Altman, Jessica Kaplan, Abaza, Yasmin
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-203361

Background: Purine-analog based IC plus VEN are effective regimens inducing deep remissions with impressive survival in single center non-randomized trials including patients (pts) with ND and R/R AML (DiNardo et. al. JCO 2021; Kadia et. al. Lancet Haem. 2021). Whether these results are more broadly extrapolatable is largely unknown. We report outcomes of a large cohort of pts treated with IC + VEN outside the context of a clinical trial. Methods: Pts with ND or R/R-AML treated with either fludarabine, cytarabine, idarubicin and G-CSF (FLAG-IDA; N=74) or cladribine, cytarabine, idarubicin (CLIA; N=9) plus VEN at two academic medical centers with baseline clinical, molecular and treatment characteristics, and survival outcomes were included. Comparisons of categorical and continuous variables utilized the Fisher exact test and Wilcoxon rank-sum or Kruskal-Wallis test as appropriate. Time to event endpoints were evaluated using the Kaplan-Meier method with Cox proportional hazards modeling for multivariable analysis (MVA). Allogeneic hematopoietic cell transplant (HCT) was considered as a time-dependent covariate. Results: 52 (63%) pts had ND and 31 (37%) had R/R-AML. Median age was 48 years (range: 20-70). ELN 2022 risk was favorable, intermediate, and adverse risk in 25% (N=21), 23% (N=19), and 52% (N=43) of the pts, respectively. Ten pts (12%; ND: 6, R/R: 4) had mutated TP53 or deletion/abnormal 17p (TP53+/17p). During induction, 81% (N=66) and 19% (N=14) of pts received VEN for 7 vs. 8-14 days, respectively. In the R/R cohort, median number of prior therapies was 1 (range: 1-5). Thirty-two percent (N=10) of pts received prior VEN and 23% (N=7) had prior HCT. In ND-AML, the CR/CRi rate was 85% (N=44; CR: 81%, CRi: 4%). CR/CRi was attained in 100% (N=12), 100% (N=14), and 69% (N=18) of pts with ELN favorable, intermediate, and adverse risk, respectively. Pts receiving 7 (N=45) vs. 8-14 days of VEN (N=7) had higher CR/CRi rates (91% vs. 43%, p: 0.007); the latter group being enriched for TP53+/17p (7% vs. 43%, p: 0.02). Accordingly, pts without TP53+/17p were more likely to attain CR/CRi (89% [N=41/46] vs. 50% [N=3/6]). Median time to count recovery (ANC ≥ 500 and/or ≥ platelets 50 x 109/L) was 23 days (range: 17-42). 30 and 60-day mortality was 1.9 and 3.8%. In R/R-AML (refractory N= 23; relapsed N=8), the overall response rate was 71% (N=22; CR: 53%, CRi: 9.6%, MLFS: 9.6%). CR/CRi rates were 89% (N=8), 80% (N=4), and 41% (N=7) in pts with ELN favorable, i