Venetoclax Plus Idarubicin and Cytarabine Chemotherapy As First-Line Treatment for Adults with Acute Myeloid Leukaemia

1. Background

3+7(idarubicin/daunorubicin plus cytarabine,IA/DA) has been a standard regimen for first line induction treatment of acute myeloid leukaemia (AML) for half a century. About 60–80% of patients with acute myeloid leukaemia reach complete remission^[1], and improved induction regimens are needed. It is in extensive exploration to combine venetocloax with standard cytotoxic drugs for fit AML patients to enhance clinical response. It is proved that venetoclax synergizes with cytarabine and idarubicin to increase antileukemic efficacy in a TP53-dependent manner ^[2].So in this study we aims to observe the efficacy and safety of lA plus venetoclax (IAV) regimen in newly diagnosed AML patients.

2. Methods

We enrolled 32 patients aged 18–60 years with previously untreated de-novo acute myeloid leukaemia and an Eastern Cooperative Oncology Group performance status of 0–2. Patients had induction treatment with intravenous Idarubicin (12 mg/m² on days 1–3), intravenous cytarabine (100 mg/m² on days 1–7), and oral venetoclax (100 mg on day 4, 200 mg on day 5, and 400 mg on days 6–11; IAV regimen). For induction therapy, the length of the treatment was 28–35 days per cycle and the number of treatment cycles was one or two. The primary endpoint was the composite complete remission rate (complete remission plus complete remission with incomplete blood cell count recovery) after one cycle of induction treatment. Secondary endpoints were bone marrow measurable residual disease by flow cytometry, event-free survival, overall survival, and adverse events

3. Findings:Between October6, 2021 andDecember 31, 2023, 32 patients were enrolled (aged16-60 years; median 46.5years), of which 11/32(34.4%) cases were in favorable risk group, 15/32(46.9%) cases were in intermediate risk group, and 6/32(18.8%) cases were in adverse risk group. 11 (38%) patients were men and 21 (62%) were women, and all were Asian.

(1). Efficacy observation: After one cycle of the lAV regimen, 87.5%(28/32) patients reached cCR, among them 90.6% patients reached MRD negative. With a median follow-up of 9 months, 24/32(75%) patints remain in CR, the median EFS and OS is not reached. The Estimated 12-months EFS is 73.3%(57.7%-93%), and 12-months OS is 86%(73.9%-100%).

(2).Safety observation: During the treatment, some patients experienced adverse reactions and complications including hematologic toxicities, liver and renal dysfunctions, febrile neutropenia. The adverse reactions was tolerated or controlled except one patient died from severe pneumonia after induction chemotherapy. Overall, the regimen was well tolerated in patients with AML at the initial diagnosis.

3. 3. conclusion

As an emerging treatment, lAV regimen is effective and safe in newly diagnosed AML patients.