Venetoclax Combined with Hypomethylation Agents As Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia - Priliminary Results from a Real World Study in China

Introduction: Venetoclax in combination with hypomethylation agents (HMAs) is a first-line induction regimen recommended by NCCN guidelines for patients aged older than 75 years or unfit for intensive chemotherapy. Since December, 2020, venetoclax has been approved in China for the treatment of AML patients who are older or unfit for intensive chemotherapy, and is gradually being used in an increasing numbers of hospitals in China. However, the efficacy and safety of venetoclax plus HMAs for the treatment of newly diagnosed adult AML patients, especially AML patients fit for intensive chemotherapy. Since January 2022, we have initiated a multicenter, prospective, observational study (No.2022219) to investigate the efficacy and safety of venetoxlax-based AML induction therapy in a real world setting. Here, we report the primary results of this study.

Methods: A total of 25 sites in 19 provinces or municipalities across China participated in this study. The study population consisted of adult patients with newly diagnosed acute myeloid leukemia who had received venetoclax and HMA induction therapy and were available for evaluation. Diagnosis was based on the 2016 World Health Organization criteria. Risk stratification was performed according to the 2017 ELN recommendations. Clinical data were retrospectively collected from the electronic healthcare system and reviewed by the principal investigator of the lead site (The First Affiliated Hospital of Soochow University). The primary endpoint was composite complete remission (CRc, including complete remission, CR, and complete remission with incomplete hematologic recovery, CRi). Statistical analyses were performed using SPSS version 26.0 (Illinois, USA) and R4.0.4 (R Foundation for Statistical Computing, Vienna, Austria). Comparisons of categorical variables between groups were performed using the chi-square test or Fisher's exact test, and the Mann-Whitney U test and the Kruskal-Wallis test were used for continuous variables. P-values less than 0.05 were considered statistically significant.

Results: Clinical data were collected from a total of 418 patients with newly diagnosed AML between January, 2022 to February, 2023. The minimum dose of venetoclax were 14 days. The baseline characteristics of all patients were shown in Table 1. The median age of all the patients were 64 (53-70 years). The was no difference in the gender distribution of patients (male to female ratio = 1.25:1). 231/418 (55.3%) patients had an ECOG score of ≥ 2 at the time of initiation of the induction treatment. 327 (80.9%) patients were considered unfit for intensive chemotherapy. 350/418 (83.7%) patients received azacitidine and venetoclax, and 12.3% of the patients received decitabine and venetoclax. Five patients were treated with specific targeted drugs along with decitabine and azacitidine, one patient was treated with flumatinib, two patients were treated with gititinib, and one patient was treated with sorafenib. A total of 384 (91.9%) de novo AML and 34 (8.2%) secondary AML patients were included in this study. According to the 2017 ELN criteria, 60 (14.4%), 114 (27.3%), and 244 (58.4%) patients were grouped to favorable, intermediate, and adverse risk groups, respectively. The overall response rate (ORR) for all patients was 77.5% (324/418). The composite complete remission (CRc) rate was 80% (48/60), 86% (98/114) and 73% (178/244) in the favorable, intermediate and adverse-risk group respectively (Figure 1A). There was no difference in CRc rates in patients with de novo AML or secondary AML(79% vs 65%, P=0.0699) (Figure 1B). Treatment responses varied among different sites (Figure 1C). The median amounts for platelet infusions and red blood cell infusions were 6.0 U (3.0-11.0 U) and 4.0 U (1.0-8.0 U). The median time of hospitalization during the induction treatment was 31 days (26-37 days). The median cost of induction treatment were $14,755 ($8,654- 22,991).

Conclusion: In this study, venetoclax in combination with a hypomethylation agent showed comparable responses across all genetic subgroups in this real-world study of China，which was compared to the results of clinical studies conducted primarily in Western countries. Currently, we have collected 800 samples in this study. We will analyze and report the short- and long-term efficacy of venetoclax plus hypomethylating agent for the treatment of newly diagnosed AML in the near future.