Efficacy and safety of bcl-2 inhibitor venetoclax combined with hypomethylating agents in treatment of myeloid neoplasms
10.3760/cma.j.cn115356-20240221-00023
- VernacularTitle:bcl-2抑制剂维奈克拉联合去甲基化药物治疗髓系肿瘤的效果和安全性
- Author:
Xiaoqing HE
1
;
Xinyou ZHANG
Author Information
1. 暨南大学第二临床医学院 深圳市人民医院血液内科，深圳 518000
- Keywords:
Leukemia, myeloid, acute;
Myelodysplastic syndromes;
Leukemia, myelomonocytic, chronic;
Antineoplastic combined chemotherapy protocols;
Proto-oncogene pro
- From:
Journal of Leukemia & Lymphoma
2024;33(12):719-725
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the efficacy and adverse reactions of bcl-2 inhibitor venetoclax (VEN) combined with hypomethylating agents (HMA) in treatment of adult myeloid neoplasms.Methods:A retrospective case series study was conducted. The clinical data of 43 patients with myeloid neoplasms treated by VEN combined with HMA in Shenzhen People's Hospital between December 2018 and December 2022 were collected. The general data, short-term efficacy, survival and adverse reactions of patients were summarized.Results:A total of 43 patients were enrolled in the study, of which 24 cases (55.8%) were male with the mean age [ M ( Q1, Q3)] of 64 years (55 years, 69 years). All 43 patients included 28 cases (65.1%) of acute myeloid leukemia (AML), 14 cases (32.6%) of high-risk myelodysplastic syndrome (HR-MDS) and 1 case (2.3%) of chronic myelomonocytic leukemia. The overall response rate (ORR) was 83.7%(36/43); the rate of complete remission (CR) / incomplete blood count recovery (CRi) or marrow complete remission (mCR) rate was 72.1% (31/43); and the negative rate of minimal residual disease (MRD) of patients achieving CR/CRi or mCR was 45.2% (14/31). The ORR of AML and HR-MDS patients was 89.3% (25/28), 71.4% (10/14), respectively; the CR/CRi or mCR rate of AML and HR-MDS patients was 75.0% (21/28) and 64.3% (9/14), respectively. The negative rate of MRD of patients achieving CR/CRi or mCR was 47.6% (10/21), 44.4% (4/9); there were no statistically significant differences in ORR, CR/CRi or mCR rates and the MRD negative rates among patients achieving CR/CRi or mCR (all P > 0.05). The median follow-up time was 30.0 months (range: 1.0-41.0 months). The median progress-free survival (PFS) and the overall survival (OS) time of all groups was 8.0 months, 15.0 months, respectively. The median PFS time was 8.5 months and 7.0 months, respectively in AML and HR-MDS patients, and the difference in PFS was statistically significant ( P = 0.154); the median OS time was 24.0 months and 10.0 months, respectively in AML and HR-MDS patients, and the difference in OS was statistically significant ( P = 0.020). The median OS was not reached in 12 patients who bridged to allogeneic hematopoietic stem cell transplantation and the median OS time was 15.0 months in 13 patients who did not undergo the transplantation; and the difference in OS between the transplantation group and non-transplantation group was statistically significant ( P = 0.008). Grade 3-4 myelosuppression occurred in 97.7% patients (42/43) in all groups and grade 3-4 agranulocytosis combined with fever occurred in 48.8% patients (21/43). In all groups, 6 patients (14.0%) developed grade 3-4 infection during treatment, and 3 HR-MDS patients of them died due to severe infection during treatment. All the non-hematological adverse reactions were grade 1-2. Conclusions:VEN+HMA regimen shows good therapeutic effects in myeloid neoplasms patients, with rapid deep remission. The prolonged survival time can be achieved in some patients who successfully bridged to allogeneic hematopoietic stem cell transplantation. The survival benefit in AML patients may be better than that in HR-MDS patients. Most myeloid neoplasms patients still suffer the different degrees of bone marrow suppression during treatment with VEN+HMA.
