Efficacy and safety of CAV (cladribine, cytarabine and venetoclax) regimen in patients with newly diagnosed Acute Myeloid Leukemia

Abstract

Abstract To explore the efficacy and safety of CAV regimen in newly diagnosed acute myeloid leukemia (AML). This study was registered in the China Clinical Trials Registry (ChiCTR2400091392). Inclusion criteria: clinically confirmed treatment- naïve AML, age ≥ 18 years. Exclusion criteria: acute promyelocytic leukemia, central nervous system leukemia. A total of fourteen patients were enrolled from August 2024 to July 2025, and two patients were transformed from chronic myeloid leukemia and myelodysplastic neoplasms, respectively. Male 5 cases, female 9 cases. Age: 49(37- 66). White blood cell (WBC) count: (0.66-188.92)×109/L, <100×109/L 11 cases, ≥100×109/L 4 cases, haemoglobin: 62-120g/L, platelets: (4-328)×109/L. One patient was nonmonocyte-like AML, while the remaining 13 patients were monocyte-like AML. Two patients did not detect chromosomal karyotyping, fusion gene and gene mutation. CBFβ::MYH11 fusion 1 case, AML::ETO fusion 2 cases, BCR::ABL fusion 2 cases, NPM1 mutation 4 cases, CEBPAbzip mutation 2 cases, FLT3-ITD mutation 2 cases, KIT mutation 1 case, ASXL1 mutation 3 cases, RUNX1 mutation 1 case, U2AF1 mutation 2 cases, STAG2 mutation 1 case, BCOR mutation 1 case, NF1 mutation 1 case, TP53 mutation 1 case, DNMT3 mutation 3 cases, IDH2 mutation 3 cases, FLT3-TKD mutation 1 case, KRAS mutation 3 cases, NRAS mutation 3 cases, ETV6 mutation 1 case, PTPN11 mutation 2 cases. According to 2022 ELN risk stratification, favorable subgroup 4 cases, intermediate subgroup 2 cases, adverse subgroup 7 cases, not evaluable 1 case. All 14 patients received chemotherapy with the CAV regimen (cladribine 5mg/m2 i.v., d1-5; cytarabine 20mg Bid i.h., d1-10; venetoclax p.o.,100mg d1, 200mg d2, 400mg d3-15). Two patients had severe cerebral thrombosis at the time of presentation and died of cerebral thrombosis on the 5th and 14th days of chemotherapy, respectively, and one patient did not complete chemotherapy. Therefore, a total of 11 patients could be evaluated for efficacy, and 10 patients obtained complete remission (CR), one patient obtained incomplete hematologic recovery complete remission (iCR). That is, regardless of the risk stratification of ELN, even patients in the adverse subgroup achieved CR/CRi. Neutrophil recovery (≥ 0.5×109/L) days: 11(5-27); platelets recovery (≥20×109/L) days: 5(-4-13), one patient had recovered platelets 4 days before the end of chemotherapy, and one patient's platelets never fell below 20×109/L from the start of chemotherapy to recovery. Only 1 patient developed mild pneumonia, 2 patients developed upper respiratory tract infection, asepemia and other infections. The follow-up time: 4(0.3-12) months. After the patient achieves CR/CRi with induction therapy, high-dose cytarabine consolidation chemotherapy or allogeneic hematopoietic stem cell transplantation was performed according to risk stratification. In addition to the aforementioned 2 patients who died of cerebral thrombosis during induction chemotherapy, there was also 1 case with cardiac insufficiency before chemotherapy and later died of cardiac insufficiency, and the rest of the patients survived disease-free until the end of follow-up. In conclusion, CAV regimen has achieved a very high CR rate in induction therapy for newly diagnosed AML, even in adverse subgroup, platelets and neutrophils recover quickly, and there is no occurrence of serious infection, but our sample number is small, and then the sample size will be further expanded to confirm the efficacy of CAV regimen in the adverse subgroup, laying the foundation for the promotion of clinical induction chemotherapy for newly diagnosed AML.