1.Efficacy analysis of selinexor combined with hypomethylating agent in the treatment of refractory/relapsed acute myeloid leukemia exposed to venetoclax.
Jian ZHANG ; Bao Quan SONG ; Xin KONG ; Yin LIU ; Han Lin YANG ; Li Hong ZONG ; Jin Yu KONG ; Yang XU ; Hui Ying QIU ; De Pei WU
Chinese Journal of Hematology 2023;44(11):936-939
3.Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience.
Wen Jing YU ; Jin Song JIA ; Jing WANG ; Fei Fei TANG ; Li Zhong GONG ; Xiao Hong LIU ; Xiao Lu ZHU ; Xiao Su ZHAO ; Xiao Jun HUANG ; Hao JIANG
Chinese Journal of Hematology 2022;43(2):134-140
Objective: To explore the safety and short-term efficacy of venetoclax combined with azacitidine (Ven+AZA) in previously untreated patients unfit for standard chemotherapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) in China. Methods: A retrospective study was conducted in 60 previously untreated patients unfit for standard chemotherapy and patients with R/R AML who received Ven+ AZA (venetoclax, 100 mg D1, 200 mg D2, 400 mg D3-28; azacitidine, 75 mg/m(2) D1- 7) at the Peking University Institute of Hematology from June 1, 2019 to May 31, 2021. The incidence of adverse events, complete remission (CR) /CR with incomplete hematological recovery (CRi) rate, objective remission rate (ORR) , and minimal residual disease (MRD) status in patients with different risk stratification and gene subtypes were analyzed. Results: The median age of the patients was 54 (18-77) years, 33 (55.0%) were males, and the median follow-up time was 4.8 (1.4-26.3) months. Among the 60 patients, 24 (40.0%) were previously untreated patients unfit for standard chemotherapy, and 36 (60.0%) were R/R patients. The median mumber cycles of Ven+AZA in the two groups were both 1 (1-5) . According to the prognostic risk stratification of the National Comprehensive Cancer Network, it was divided into 8 cases of favorable-risk, 2 cases of intermediate risk, and 14 cases of poor-risk. In previously untreated patients unfit for standard chemotherapy, after the first cycle of Ven+AZA, 17/24 (70.8%) cases achieved CR/CRi, 3/24 (12.5%) achieved partial remission (PR) , and the ORR was 83.3%. Among them, nine patients received a second cycle chemotherapy and two received a third cycle. Among CR/CRi patients, 8/17 (47.1%) achieved MRD negativity after two cycles of therapy. In the R/R group, after the first cycle of Ven+AZA, 21/36 (58.3%) cases achieved CR/CRi (7/21 achieved MRD negativity) , 3 achieved PR, and the ORR was 66.7%. Among R/R patients, 12 were treated for more than two cycles. There were no new CR/CRi patients after the second treatment cycle, and 14 cases (66.7%) achieved MRD negativity. According to the time from CR to hematological recurrence, the R/R group was divided into 12 cases in the favorable-risk group (CR to hematological recurrence ≥18 months) and 24 in the poor-risk group (CR to hematological recurrence<18 months, no remission after one cycle of therapy, and no remission after two or more cycles of therapy) . Eleven of 24 (45.8%) cases achieved CR/CRi after one cycle of Ven+AZA in the poor-risk R/R group, and 10 of 12 (83.3%) achieved CR/CRi in the favorable-risk R/R group, which was significantly superior to the poor-risk group (P=0.031) . After one cycle of treatment, 13 patients with IDH1/2 mutations and 4 that were TP53-positive all achieved CR/CRi. The CR/CRi rate of 18 patients with NPM1 mutations was 77.8%. Five patients with RUNX1-RUNX1T1 combined with KIT D816 mutation (two initial diagnoses and three recurrences) had no remission. Ven+ AZA was tolerable for AML patients. Conclusion: Ven+AZA has acceptable safety in previously untreated patients unfit for standard chemotherapy, patients with R/R AML can achieve a high response rate, and some patients can achieve MRD negativity. It is also effective in NPM1-, IDH1/IDH2-, and TP53-positive patients. The long-term efficacy remains to be observed.
Aged
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Azacitidine/therapeutic use*
;
Bridged Bicyclo Compounds, Heterocyclic/therapeutic use*
;
Humans
;
Leukemia, Myeloid, Acute/genetics*
;
Male
;
Middle Aged
;
Retrospective Studies
;
Sulfonamides
7.Research Advance of Venetoclax in Hematological Tumors--Review.
Ling-Yun CHEN ; Yong-Ping SONG
Journal of Experimental Hematology 2020;28(4):1419-1423
Venetoclax is a selective inhibitor of the anti-apoptotic protein B-cell lymphoma 2（BCL-2）and has great potential in treating a variety of hematological tumors. In recent years, domestic and foreign scholars have tried to use venetoclax singal or in combination with some drugs to treat the patients with hematological tumors, including elderly acute myeloid leukemia（AML）patients un suitable for intensive chemotherapy, relapsed or refractory chronic lymphocytic leukemia（CLL）, Non-Hodgkin's lymphoma（NHL）and multiple myeloma（MM）patients, these studies have achieved good results．At the same time，some scholars found that the secondary drug-resistance occurred in some patients who continuous treated with Venetoclax, and explored the Venetoclax-resistant mechanism. In this review, the research advance of Venetoclax in hematological tumors and the mechanisms of drug resistance are summarized and discussed briefly.
Aged
;
Antineoplastic Agents
;
therapeutic use
;
Bridged Bicyclo Compounds, Heterocyclic
;
therapeutic use
;
Hematologic Neoplasms
;
Humans
;
Leukemia, Lymphocytic, Chronic, B-Cell
;
drug therapy
;
Sulfonamides
10.Clinical Observation of Venetoclax Combined with Demethylating Agents on the Treatment of Relapsed/Refractory Acute Myeloid Leukemia.
Yao WANG ; Sai-Lan HUANG ; Xing-Xia ZHANG ; Mei-Ru BIAN ; Guo-Qiang LIN ; Ye-Jun SI ; Bing ZHANG ; Yan WAN ; Li WANG ; Yan-Ming ZHANG
Journal of Experimental Hematology 2023;31(2):327-332
OBJECTIVE:
To investigate the efficacy and safety of venetoclax (VEN) combined with demethylating agents (HMA) in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML).
METHODS:
The clinical data of 26 adult R/R AML patients who received the combination of VEN with azacitidine (AZA) or decitabine (DAC) in Huai'an Second People's Hospital from February 2019 to November 2021 were retrospectively analyzed. The treatment response, adverse events as well as survival were observed, and the factors of influencing the efficacy and survival were explored.
RESULTS:
The overall response rate (ORR) of 26 patients was 57.7% (15 cases), including 13 cases of complete response (CR) and CR with incomplete count recovery (CRi) and 2 cases of partial response (PR). Among the 13 patients who got CR/CRi, 7 cases achieved CRm (minimal residual disease negative CR) and 6 cases did not, with statistically significant differences in overall survival (OS) and event-free survival (EFS) between the two groups (P=0.044, 0.036). The median OS of all the patients was 6.6 (0.5-15.6) months, and median EFS was 3.4 (0.5-9.9) months. There were 13 patients in the relapse group and refractory group, respectively, with response rate of 84.6% and 30.8% (P=0.015). The survival analysis showed that the relapse group had a better OS than the refractory group (P=0.026), but there was no significant difference in EFS (P=0.069). Sixteen patients who treated for 1-2 cycles and 10 patients who treated for more than 3 cycles achieved response rates of 37.5% and 90.0%, respectively (P=0.014), and patients treated for more cycles had superior OS and EFS (both P<0.01). Adverse effects were mainly bone marrow suppression, complicated by various degrees of infection, bleeding, and gastrointestinal discomfort was common, but these could be all tolerated by patients.
CONCLUSION
VEN combined with HMA is an effective salvage therapy for patients with R/R AML and is well tolerated by patients. Achieving minimal residual disease negativity is able to improve long-term survival of patients.
Adult
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Humans
;
Retrospective Studies
;
Neoplasm, Residual/drug therapy*
;
Bridged Bicyclo Compounds, Heterocyclic/adverse effects*
;
Recurrence
;
Leukemia, Myeloid, Acute/drug therapy*
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
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