PMID- 38471289 OWN - NLM STAT- MEDLINE DCOM- 20240422 LR - 20240422 IS - 1879-0852 (Electronic) IS - 0959-8049 (Linking) VI - 202 DP - 2024 May TI - Venetoclax plus cytarabine and azacitidine in relapsed/refractory AML: An open-label, single-arm, phase 2 study. PG - 113979 LID - S0959-8049(24)00135-7 [pii] LID - 10.1016/j.ejca.2024.113979 [doi] AB - BACKGROUND: The outcome of relapsed/refractory (R/R) acute myeloid leukemia (AML) remains extremely poor. Venetoclax (VEN)-based regimens have shown promise in treating R/R AML. OBJECTIVE: This phase 2 study aimed to systematically evaluate the efficacy and safety of the VAA regimen (VEN plus Cytarabine and Azacitidine) in R/R AML patients. METHODS: Thirty R/R AML patients were enrolled. The study adopted a stepwise ramp-up of VEN dosing, starting with 100 mg on day 1, escalating to 200 mg on day 2, and reaching 400 mg from day 3 to day 9. Cytarabine (10 mg/m(2), q12h) was administered intravenously twice daily from days 1 to 10, and Azacitidine (75 mg/m(2)) was administered via subcutaneous injection once daily from days 1-7. The primary efficacy endpoint was the composite complete remission rate (CRc), including complete response (CR) and complete response with incomplete blood count recovery (CRi). Secondary endpoints included overall survival (OS), duration of response (DOR), and safety analysis. RESULTS: The CRc rate was 63.3% (19/30), with CR in 36.7% of patients and CRi in 26.7%. Notably, 14 (73.7%) of 19 patients achieving CRc showed undetectable measurable residual disease by flow cytometry. With a median follow-up of 10.7 months, the median OS had not been reached, and the median DOR was 18.3 months. The most common grade 3-4 adverse events (AEs) were neutropenia (100%), anemia (96.7%), thrombocytopenia (90.0%), and leukopenia (90.0%). Infections, with pneumonia being the most prevalent (43.3%), were observed, including one fatal case of Pseudomonas aeruginosa septicemia. There were no treatment-related deaths. CONCLUSION: The VAA regimen is an effective and safe option for patients with R/R AML, demonstrating a high CRc rate and manageable safety profile. CI - Copyright (c) 2024. Published by Elsevier Ltd. FAU - You, Liangshun AU - You L AD - Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Provincial Clinical Research Center for Hematologic Diseases, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Province Key Laboratory of Hematology Oncology Diagnosis and Treatment, Hangzhou 310003, Zhejiang, People's Republic of China. FAU - Liu, Yi AU - Liu Y AD - Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Provincial Clinical Research Center for Hematologic Diseases, Hangzhou 310003, Zhejiang, People's Republic of China. FAU - Mai, Wenyuan AU - Mai W AD - Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Provincial Clinical Research Center for Hematologic Diseases, Hangzhou 310003, Zhejiang, People's Republic of China. FAU - Xie, Wanzhuo AU - Xie W AD - Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Provincial Clinical Research Center for Hematologic Diseases, Hangzhou 310003, Zhejiang, People's Republic of China. FAU - Zhou, De AU - Zhou D AD - Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Provincial Clinical Research Center for Hematologic Diseases, Hangzhou 310003, Zhejiang, People's Republic of China. FAU - Mao, Liping AU - Mao L AD - Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Provincial Clinical Research Center for Hematologic Diseases, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Province Key Laboratory of Hematology Oncology Diagnosis and Treatment, Hangzhou 310003, Zhejiang, People's Republic of China. FAU - Chen, Lili AU - Chen L AD - The First People's Hospital of Taizhou, Huangyan District, Zhejiang China. FAU - Zhou, Xinping AU - Zhou X AD - Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Provincial Clinical Research Center for Hematologic Diseases, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Province Key Laboratory of Hematology Oncology Diagnosis and Treatment, Hangzhou 310003, Zhejiang, People's Republic of China. FAU - Ma, Liya AU - Ma L AD - Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Provincial Clinical Research Center for Hematologic Diseases, Hangzhou 310003, Zhejiang, People's Republic of China. FAU - Zheng, Xiaolong AU - Zheng X AD - Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Provincial Clinical Research Center for Hematologic Diseases, Hangzhou 310003, Zhejiang, People's Republic of China. FAU - Wei, Juying AU - Wei J AD - Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Provincial Clinical Research Center for Hematologic Diseases, Hangzhou 310003, Zhejiang, People's Republic of China. FAU - Lou, Yinjun AU - Lou Y AD - Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Provincial Clinical Research Center for Hematologic Diseases, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Province Key Laboratory of Hematology Oncology Diagnosis and Treatment, Hangzhou 310003, Zhejiang, People's Republic of China. FAU - Ye, Xingnong AU - Ye X AD - Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Provincial Clinical Research Center for Hematologic Diseases, Hangzhou 310003, Zhejiang, People's Republic of China. FAU - Tong, Hongyan AU - Tong H AD - Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Provincial Clinical Research Center for Hematologic Diseases, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Province Key Laboratory of Hematology Oncology Diagnosis and Treatment, Hangzhou 310003, Zhejiang, People's Republic of China. Electronic address: hongyantong@aliyun.com. FAU - Jin, Jie AU - Jin J AD - Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Provincial Clinical Research Center for Hematologic Diseases, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Province Key Laboratory of Hematology Oncology Diagnosis and Treatment, Hangzhou 310003, Zhejiang, People's Republic of China. Electronic address: jiej0503@zju.edu.cn. FAU - Meng, Haitao AU - Meng H AD - Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Provincial Clinical Research Center for Hematologic Diseases, Hangzhou 310003, Zhejiang, People's Republic of China; Zhejiang Province Key Laboratory of Hematology Oncology Diagnosis and Treatment, Hangzhou 310003, Zhejiang, People's Republic of China. Electronic address: menghait2004@zju.edu.cn. LA - eng PT - Clinical Trial, Phase II PT - Journal Article DEP - 20240301 PL - England TA - Eur J Cancer JT - European journal of cancer (Oxford, England : 1990) JID - 9005373 RN - 04079A1RDZ (Cytarabine) RN - M801H13NRU (Azacitidine) RN - N54AIC43PW (venetoclax) RN - 0 (Bridged Bicyclo Compounds, Heterocyclic) RN - 0 (Sulfonamides) SB - IM MH - Humans MH - Cytarabine/adverse effects MH - Azacitidine MH - *Leukemia, Myeloid, Acute/drug therapy MH - Bridged Bicyclo Compounds, Heterocyclic/adverse effects MH - Pathologic Complete Response MH - *Leukopenia/chemically induced MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects MH - *Sulfonamides OTO - NOTNLM OT - Azatidine OT - Cytarabine OT - Relapsed and Refractory AML OT - Venetoclax COIS- Declaration of Competing Interest The authors declare that they have no competing interests. EDAT- 2024/03/13 00:44 MHDA- 2024/04/22 06:44 CRDT- 2024/03/12 19:03 PHST- 2023/11/07 00:00 [received] PHST- 2024/01/27 00:00 [revised] PHST- 2024/02/26 00:00 [accepted] PHST- 2024/04/22 06:44 [medline] PHST- 2024/03/13 00:44 [pubmed] PHST- 2024/03/12 19:03 [entrez] AID - S0959-8049(24)00135-7 [pii] AID - 10.1016/j.ejca.2024.113979 [doi] PST - ppublish SO - Eur J Cancer. 2024 May;202:113979. doi: 10.1016/j.ejca.2024.113979. Epub 2024 Mar 1.