Clia plus venetoclax for AML: Feasibility and efficacy in a hybrid community setting

Abstract

Abstract Background: The addition of venetoclax (VEN) to purine-analog-based intensive chemotherapy has demonstrated safety and efficacy in phase 2 trials for newly diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) (DiNardo et al., JCO 2021; Kadia et al., Lancet Haematol 2021). These studies reported high measurable residual disease (MRD) negativity and low treatment-related mortality (TRM), supporting its use in the frontline setting. Whether these outcomes translate to community-based practice remains unclear. We report real-world outcomes of patients treated with CLIA-VEN at a hybrid community oncology center. Methods: We conducted a retrospective single-center study of adults with newly diagnosed AML or mixed phenotype acute leukemia (MPAL) with a predominant myeloid component who received CLIA-VEN between January 1, 2019, to December 31, 2023. Induction consisted of cladribine 5 mg/m2 IV (days 1-5), cytarabine 1-1.5 g/m2 IV (days 1-5), and idarubicin 10 mg/m2 IV (days 1-3), and venetoclax 400 mg PO (days 2-8; dose-adjusted for azole use). Consolidation included 3 days of CLIA , with cladribine dose 0.75-1 g/m2. Seven patients did not receive idarubicin as part of consolidation. Among those who received idarubicin, it was generally limited to 1-2 cycles. Primary endpoints were overall response rate (ORR), complete remission (CR), CR with incomplete hematologic recovery (CRi), MRD status, progression-free survival (PFS) and overall survival (OS). Results: Fifteen patients received frontline CLIA-VEN; median age was 51 years (range 33-61), and 73% identified as Hispanic or Latino. Two patients (13%) had MPAL, and three (20%) had secondary/therapy-related AML. By European Leukemia Network (ELN) 2022 criteria, 40% were favorable risk, 13% intermediate, and 47% adverse. NPM1 mutations were most common (33%), followed by IDH1, KMT2A, and DNMT3A (20% each); FLT3-ITD occurred in 13%. Median follow-up was 17.2 months (range 1.6-30.3). ORR was 100%, with CR/CRi in 94%. Among patients who underwent high sensitivity MRD testing, the MRD negativity rate was 67%. All patients achieved MRD negativity during or after consolidation (including consolidative alloSCT). After a median of 2 cycles of consolidation (range 1-5 cycles), 8 patients (53%) proceeded to allogeneic stem cell transplantation (alloSCT). The majority of patients (75%) received myeloablative conditioning. Seventy-five percent of patients were MRD negative at the time of transplant. Grade 3/4 non-hematologic toxicities included febrile neutropenia (100%, n=15), infection (53%, n=8), and elevated AST (7%, n=1). No TRM was observed. Median PFS and OS were not reached; 1-year PFS and OS were both 93.3% (95% CI: 68-99%) as only 1 subject died from AML progression at 143 days.Conclusion: CLIA-VEN was well tolerated and yielded high MRD-negative remission rates in a hybrid community oncology setting, with encouraging survival outcomes and successful bridging to alloSCT. The absence of TRM and the high proportion of patients achieving MRD negativity mirror outcomes reported in academic phase 2 studies, suggesting that such results are achievable outside specialized tertiary centers. These findings underscore the feasibility of implementing intensive VEN-based regimens in hybrid community practices, where logistical constraints and patient demographics may differ from those in trial populations. Broader adoption of CLIA-VEN in community settings has the potential to improve curative-intent treatment access for AML patients and warrants further validation in larger multicenter real-world cohorts.