Efficacy and Safety of cladribine combined with cytarabine and G-CSF in Eliminating Measurable Residual disease for Core-binding factor acute myeloid leukemia: A retrospective, single-arm, multicenter study

Abstract Background Persistent measurable residual disease (MRD) in core-binding factor acute myeloid leukemia (CBF-AML) is closely associated with increased risk of relapse.This study aims to evaluate the efficacy and safety of cladribine combined with cytarabine and G-CSF (CLAG) regimen in eliminating MRD for CBF-AML.Methods This study is a retrospective, single-arm, multicenter clinical study from 6 hospitals in China. CBF-AML patients aged 18–65 years old who have achieved complete remission (CR) after anthracycline and cytarabine based chemotherapy but with persistent MRD were enrolled in this study. All patients received one cycle of CLAG regimen: cladribine at 5 mg/m²/d on days 1-5, cytarabine at 1 g/m²/d intravenous infusion over 2-4 hours on days 1-5 and granulocyte colony-stimulating factor (G-CSF) at 300 μg/d subcutaneous injection on days 0-5. MRD was monitored by quantitative PCR for RUNX1/RUNX1T1or CBFB-MYH11transcripts, presented as RUNX1/RUNX1T1/ABL or CBFB-MYH11/ABL ratio. Complete molecular remission (CMR) was defined as RUNX1/RUNX1T1/ABL or CBFB-MYH11/ABL ratio of less than 0.001%. Molecular response (MR) was defined as > 1 log10 decrease of RUNX1/RUNX1T1/ABL or CBFB-MYH11/ABL ratio. The primary endpoint was the CMR rate after 1 cycle of CLAG treatment. The secondary endpoints included MR rate, overall survival (OS), cumulative incidence of relapse (CIR) and the incidence of adverse events (AEs).Results A total of 26 cases including 19 with t(8;21) and 7 with inv(16) AMLwere enrolled in this study. The median age was 46 years old (20-62). At the start of CLAG regimen, the median cycle of anthracycline and cytarabine-based intensive chemotherapy was 4 (ranged 3-9), and the median RUNX1/RUNX1T1/ABL or CBFB-MYH11/ABL ratio was 6.83%. 17 out of 26 patients (65.4%) achieved CMR and 18 out of 26 (69.2%) achieved MR after 1 cycle of CLAG regimen.With a median follow-up of 19.73 months (range, 4.2-42.7 months ), 15 out of 17 patients retained in CMR and 2 experienced molecular relapse. Patients obtaining CMR had a trend toward higher 1-year RFS (100% vs 77.78%, p = 0.098) and OS(100.0% vs 87.5%, p = 0.301) than that not obtaining CMR. In terms of grade 3-4 adverse events, grade 4 neutropenia and thrombocytopenia after CLAG were observed in more than 90% of cases. The most common grade 3-4 non-hematological adverse events were fever (83.6%), pneumonia (17.5%), and bloodstream infection (16.1%), respectively. Treatment-related deaths were not observed.Conclusions CLAG regimen might be an effective and well tolerated regimen for eliminating MRD in CBF-AML . Keywords: Cladribine, MRD, CBF-AML, CMR, adverse events