The Efficacy and Safety of CLAG±Ida/Mito+Ven As Salvage Therapy of Relapsed/Refractory Acute Myeloid Leukemia

Purpose: As known CLAG±Ida/Mito regimen is recommended by different guidelines as a chioce for salvage therapy of relapsed/refractory acute myeloid leukemia (RR-AML). Recent study showed venetoclax (Ven) added to CLAG+Ida as frontline treatment of AML acquired a good response and well toleration. Yet, how CLAG±Ida/Mito+Ven works in the salvage therapy of RR-AML remains unclear. Aim of this study was to analyze the efficacy and safety of CLAG±Ida/Mito+Ven as salvage therapy of RR-AML.

Methods: A single center, retrospective study was performed. Patients with RR-AML, who were salvagedly treated with CLAG±Ida/Mito+Ven during July 2021 to June 2023, were included. CLAG±Ida/Mito+Ven: cladribine 5mg/m ² day 1-5, cytarabine 1-1.5g/m ² day 1-5, PEG-G-CSF 6mg day 0, idarubicin 6mg/m ² day 1-3 or mitoxantrone 6mg/m ² day 1-3 (lipo-Mito 20mg/m ² day 1), Ven 400mg day 2-8.

Results: 33 patients were included, with a median age of 42(15-72) years old, male to female 17/16, de novo/sAML 31/2, refractory/relapsed 17/16, ELN-low /intermediate/high risk 7/10/16. They previously received median 2(1-12) cycles of chemotherapy, including 2 relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT), 14 with prior hypomethylating agents (HMA). Among the 33 patients with CLAG+Ven, 3 were combined with Mito, 1 with Ida, 15 with FLT3 inhibitors. After one cycle of salvage therapy, 24(72.7%) acquired response, including 22(66.7%) with CR/CRi, 15(45.5%) with MRD-negative (accounting for 68.2% of the patients with CR/CRi). Multivariate analysis showed that prior HMA, FLT3 mutation and ELN-high risk were the independently poor factors for CR/CRi. With a median follow-up of 3(1-23) months, 15(45.5%) patients were bridged to allo-HSCT, 3(12.5%) relapsed, 5(15.2%) died, including 3 died of leukemia progression and 2 with transplant-related motality. Patients obtaining CR/CRi had significantly longer overall survival (mOS, 19.8(15.8-23.8) months) than those without (mOS, 5.1(2.7-7.5) months, P=0.013). Patients being bridged to allo-HSCT also had significantly better OS than those without. During the salvage therapy, the median duration of agranulocytosis was 19(11-40) days. 25(75.6%) patients underwent manageable infection. The motality of the 30 and 60 day were 0.

Conclusion: CLAG±Ida/Mito+Ven might be a chioce for salvage therapy of RR-AML, with the CR/CRi rate of 66.7%, MRD-negative rate of 68.2% and well toleration.

Key words: CLAG, venetoclax, salvage therapy, relapsed/refractory, acute myeloid leukemia