Treatment Response and Impact Factor of Venetoclax Based Regimens in the Frontline Treatment of Newly Diagnosed Unfit Acute Myeloid Leukemia in the Real World of China

Purpose: Aim to assess the efficacy and safety of venetoclax (VEN) based regimens in the frontline treatment of newly diagnosed (ND) unfit acute myeloid leukemia (AML), and then explore the impact factors of the efficacy in the real world of China.

Method: All patients with ND-unfit-AML being frontline treated with VEN-based regimens from July 2019 to February 2022 in Nanfang Hospital were included and analyzed their treatment response, safety and the impact factors of efficacy.

Results: Totally 73 patients with a median age of 64(13-84) years old (54(74.0%) patients with Eastern Cooperative Oncology Group (ECOG) performance score (PS) of 0-2 and 19(26.0%) with ECOG PS of 3-4) were frontline treated with a median of 2(1-8) cycles of VEN-based therapy, including 68(93.2%) with VEN+azacytidine and 5(6.8%) with VEN+decitabine. 32(43.8%) patients terminated VEN-based therapy, including 26(35.6%) cases were adjusted their treatment strategy, and 20(27.4%) patients were bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT). With a median follow-up of 8.0(1.0-31.0) months, a total of 56(76.7%) patients acquired treatment response, including 48(65.8%) with complete remission (CR)/CR with incomplete count recovery (CRi) and 30/71(42.3%) with measurable residual disease (MRD) negative. The median time of acquiring CR/CRi was 1(1-5) cycle of therapy. The rate of CR/CRi and MRD negative were increasing with rising cycles of therapy. Patients with low risk (vs intermediate risk and high risk) according to European Leukemia Net stratification, mutation of IDH1/2, NPM1 and FLT3-ITD/TKD, and 28 days of VEN (vs 14-21 days) had better response to VEN-based therapy. There were not significantly different in the rate CR/CRi and MRD negative between the patients with de novo versus secondary/treatment-related AML, the dose of VEN with 400mg/d versus 100-200mg/d (co-administered with posaconazoleorvoriconazole). The median overall survival (mOS) was 20.3±1.8 months. The rate of one year OS was 62.5%±7.5%. The patients with acquiring CR/CRi (P<0.001) or MRD negative (P=0.001 had significantly better mOS than those without. The patients with treatment strategy adjustment had much longer mOS (P=0.011) and lower rate of relapse (p=0,020) than those with continuous VEN-based therapy, especially remarkably in the patients with the age <60 years old or high risk. Bridging to allo-HSCT further improved mOS versus those without (P=0.010). The safety of VEN-based therapy was well tolerated and the incidence of ≥3 grade adverse events was low.

Conclusion: VEN-based therapy as the frontline treatment of ND-unfit-AML in the real world was effective and safe. Molecular abnormalities, treatment strategy and whether standardized use of VEN or not could significantly impact the efficacy of VEN-based therapy.

Key words: Venetoclax, unfit, acute myeloid leukemia, efficacy, safety

No relevant conflicts of interest to declare.