AUTHORS
Xiao Han, Pan Zhao2, Xue Liu3, Siyu Chen4, Ying Zhang5, Zhang Mengyun6, Hong Liu7, Cheng Zhang, MD8, Yaming Xi9, Wen Qin, MD10, Xi Zhang, MD11
AFFILIATIONS
1 Lanzhou University First Hospital, Lanzhou, Gansu, China, Xinqiao Hospital Army Medical University, Chongqing, China
2 Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
3 Xinqiao Hospital Army Medical University, Chongqing, China
4 Xinqiao Hospital Army Medical University, Chongqing, China
5 The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
6 Xinqiao Hospital Army Medical University, Chongqing, China
7 Xinqiao Hospital Army Medical University, Chongqing, China
8 Xinqiao Hospital Army Medical University, Chongqing, China
9 Lanzhou University First Hospital, Lanzhou, Gansu, China
10 Xinqiao Hospital Army Medical University, Chongqing, China
11 Lanzhou University First Hospital, Lanzhou, Gansu, China, Xinqiao Hospital Army Medical University, Chongqing, China
ABSTRACT
Objective
Venetoclax plus azacitidine (VA) serves as first-line therapy for elderly unfit patients with acute myeloid leukemia (AML). Our preliminary data showed that adding low-dose cytarabine to VA (VAA regimen) improved remission and MRD-negative rates versus VA. Given the lack of optimized low-intensity regimens for younger unfit patients with newly diagnosed AML, we hypothesized that the VAA regimen could enhance treatment outcomes and increase the MRD-negative CR/CRi rate in this population.
Methods
This is a phase II study investigating the combination of cytarabine and venetoclax plus azacitidine in unfit younger patients with newly diagnosed AML (ChiCTR2200063804). The rolled patients received a 28-day cycle with Cytarabine (10mg/m2 q12h on D1-7), Azacitidine (75mg/m2 on D1-7), and Venetoclax (100mg on D1, 200mg on D2, and 400mg on D3-28). The primary endpoint was the CR/CRi with MRD-negative rate after induction treatment; Secondary endpoints were CRc rate and ORR, overall survival(OS), event-free survival(EFS), duration of response (DoR), and toxicity.
Results
A total of 96 patients were treated and assessed; median age was 52.5 years (range, 18-59 years). By ELN 2022, 36.5%, 37.5%, and 26% were favorable, intermediate, and adverse risk, respectively. The ORR (CR + CRi + PR) was 84.4% (81/96) after one cycle of the regimen. The CRc rate was 78.1% (75/96). Among the 75 patients who achieved CRc, 56 (74.7%) had negativity for MRD. With a median follow-up of 12 [IQR, 6.2-22] months, the median OS and EFS were not yet reached and 13.4 (NE-NE) months, while the median DoR was not yet reached. The estimated 1-year and 2-year OS rates were 72.2% and 55.4%, respectively. No treatment-related deaths occurred within 4 weeks. The hematologic AEs were common and included neutropenia (79.2%), thrombocytopenia (70.8%), and anemia (56.2%). The most frequent grade 3/4 non-hematologic toxicities were febrile neutropenia (55.2%), pneumonia (9.4%), and elevated bilirubin (3.1%).
Conclusion
Venetoclax plus azacitidine and cytarabine is an effective regimen among unfit younger patients with newly diagnosed AML. The rates of CRc with MRD-negative is encouraging and AEs are controllable. Further randomized controlled study in these populations, as well as comparisons to standard frontline therapies is warranted.
DISCLOSURES
Xiao Han: No relevant conflicts of interest to declare.