Efficacy and safety of clia plus venetoclax as salvage therapy for relapsed or refractory Acute Myeloid Leukemia

Abstract

Abstract Background: Relapsed or refractory acute myeloid leukemia (R/R AML) carries poor outcomes, with standard salvage regimens yielding complete remission (CR) rates of only 20–30% and median overall survival (OS) of less than 6 months. Venetoclax combined with cladribine, idarubicin, and cytarabine (CLIA-ven) has shown promising efficacy in newly diagnosed AML. Its role in the salvage setting, however, remains uncertain. Methods We retrospectively reviewed adult patients (≥18 years) with R/R AML treated with CLIA-ven at our institution between June 2023 and July 2025. AML was diagnosed per 2016 World Health Organization criteria, and risk stratification was performed according to European LeukemiaNet 2022. Measurable residual disease (MRD) was assessed by multicolor flow cytometry (sensitivity 0.02%). Outcomes included CR/CR with incomplete hematologic recovery (CRi), MRD negativity, relapse-free survival (RFS), and overall survival (OS). RFS and OS were estimated using the Kaplan–Meier method. Induction consisted of cladribine 5 mg/m² IV days 1–5, idarubicin 10 mg/m² days 1–3, cytarabine 1500 mg/m² days 1–5, and venetoclax 400 mg PO daily days 2-8. Following induction, up to five 28-day consolidation cycles (cladribine 5 mg/m² days 1–3, idarubicin 8 mg/m² days 1–2, cytarabine 1000 mg/m² days 1–3, and venetoclax 400 mg PO days 2–8) could be offered. All cycles were inpatient with TLS monitoring; venetoclax ramp-up was omitted. Venetoclax doses were reduced to 200 mg with fluconazole and 70 mg with posaconazole prophylaxis. Results Sixteen patients were treated. The median age was 46 years (range: 24–68); 75% were male. At diagnosis, 44% had adverse-risk, 44% intermediate-risk, and 12% favorable-risk AML. Fifty-six percent had de novo AML; the remainder had secondary AML (MDS 19%, MPN 19%, CMML 6%). Approximately 39% had extramedullary disease. Complex cytogenetics were present in 19%. Most commonly mutated genes included NRAS (25%), FLT3 (15%), WT1 (19%), JAK2 (19%), U2AF1 (13%), DNMT3A (13%), and TP53 (13%). Median prior therapy lines were 2 (range 1–5). 50% had prior venetoclax, 94% prior anthracycline, and 19% prior allogeneic transplant. Three patients had primary refractory disease. CLIA-ven was started a median of 7.7 months (range: 2.2 to 99 months) following the initial diagnosis with AML. The CR/CRi rate was 76%, with 38% achieving CR. Among 11 evaluable patients, 7 (64%) achieved MRD negativity. Six patients underwent CLIA-ven consolidation with a median of 2 cycles of consolidation received (range: 1-5). Three patients underwent allogeneic transplant and remain in remission. No treatment-related deaths occurred, and toxicities were manageable. At a median follow-up of 8.8 months (95% CI: 2.3–NR), 9 patients relapsed. The median RFS was 4.3 months (95% CI: 3.3–NR) and median OS 12.3 months (95% CI: 5.1–NR). The 6month OS was 62%. Conclusion CLIA-ven appears to be an effective and well-tolerated salvage regimen in a heavily pretreated cohort with relapsed/refractory AML, achieving high rates of remission with a substantial proportion achieving MRD negativity. While only a minority of patients proceeded to allogeneic transplant in this series, the regimen may provide an important option for achieving remission and facilitating transplant candidacy.