Venetoclax plus hypomethylating agent for the salvage treatment of relapsing myeloid malignancies after hematopoietic stem cell transplantation: A multicenter retrospective study on behalf of the Zhejiang Cooperative Group for Blood and Marrow Transplantation

Gao, Fei; Gao, Yang; Luo, Yi; Yu, Jian; Fu, Haidong; Lai, Xiaoyu; Liu, Lizhen; Ye, Baodong; Lan, Jianping; Song, Xiaolu; Lu, Ying; Chen, Lieguang; Chen, Yi; Kang, Yu; Huang, He; Shi, Jimin; Zhao, Yanmin

doi:10.1002/ajh.26405

Cited by 8 publications

(10 citation statements)

References 8 publications

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“…However, 72% of patients experienced severe infections, and 78% of patients died after a median follow-up of 8.4 months (113). We have recently reported 44 patients (AML, n = 34) with post-allo-HCT relapse who received salvage venetoclax/HMA, which achieved a CR/ CRi incidence of 34.1% (114).…”

Section: Bcl-2 Inhibitorsmentioning

confidence: 99%

Optimization of Donor Lymphocyte Infusion for AML Relapse After Allo-HCT in the Era of New Drugs and Cell Engineering

Yang

Yuan

et al. 2022

Front. Oncol.

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Donor lymphocyte infusion (DLI) is a key strategy for the treatment of AML relapse after allogeneic hematopoietic cell transplantation (allo-HCT) and has been used for either prophylactic, pre-emptive, or therapeutic purposes. However, the prognosis of these patients remains dismal even after DLI infusion (2-year overall survival, ~25%), and the efficacy is achieved at the cost of toxicities such as graft-versus-host (GVH) disease. Attempts to optimize DLI efficacy and safety, such as dose/timing modification and the use of cytoreduction, before DLI have been performed previously. Recently, a great number of novel targeted and immunomodulatory agents have emerged. Some of them, such as hypomethylating agents, FLT3 and Bcl-2 inhibitors, have been used in combination with DLI, aiming to enhance the graft-versus-leukemia effect. Moreover, manipulation of the DLI graft through cell selection (e.g., donor NK cells) or cell engineering (donor CAR-T cells) has shown potentially superior anti-tumor effects but less GVH effect than conventional DLI in clinical trials. This review summarizes the recent advances on the use of DLI for the prophylaxis/treatment of AML relapse and discusses future strategies which may further improve the treatment efficacy.

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Section: Bcl-2 Inhibitorsmentioning

confidence: 99%

Optimization of Donor Lymphocyte Infusion for AML Relapse After Allo-HCT in the Era of New Drugs and Cell Engineering

Yang

Yuan

et al. 2022

Front. Oncol.

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“…Recent studies have shown encouraging treatment effects in relapsed/refractory (R/R) AML and elderly patients with combined HMAs/VEN ( 95 , 96 ), while the clinical value for HMAs/Ven in the transplantation setting has been explored preliminarily, and a phase 3, randomized clinical study of HMAs/VEN in AML posttransplantation (NCT04161885) is now ongoing. In a recent multicenter retrospective study from China ( 70 ), TP53 mutation (HR = 17.339, p =.033) and relapse within 1 year posttransplantation (HR = 6.261, p =.026) were identified as independent risk factors when HMAs/VEN was used in relapsed AML or MDS patients. The results from Esther Schuler et al.…”

Section: Post-hsctmentioning

confidence: 99%

“…There is now substantial evidence showing that patients who are molecular relapsed/hematological relapse with lower blast count or a longer interval from HSCT to relapse might be associated with better survival when HMAs-based therapies are used in relapsed AML or MDS ( 61 – 63 , 69 , 70 , 97 ). Thus, for molecular relapsed (bone blast<5%) MDS or AML according to MRD determination, intervention strategies should be recommended and implemented as early as possible.…”

Section: Post-hsctmentioning

confidence: 99%

Generalist in allogeneic hematopoietic stem cell transplantation for MDS or AML: Epigenetic therapy

et al. 2022

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative treatment for patients with myeloid malignancies such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, relapse and graft-versus-host disease (GvHD) still affect the survival of patients who receive allo-HSCT, and more appropriate therapeutic strategies should be applied at all stages of transplantation to prevent these adverse events. The use of epigenetics agents, such as hypomethylating agents (HMAs), has been explored to decrease the risk of relapse by epigenetic modulation, which is especially effective among AML patients with poor mutations in epigenetic regulators. Furthermore, epigenetic agents have also been regarded as prophylactic methods for GvHD management without abrogating graft versus leukemia (GvL) effects. Therefore, the combination of epigenetic therapy and HSCT may optimize the transplantation process and prevent treatment failure. Existing studies have investigated the feasibility and effectiveness of using HMAs in the pretransplant, transplant and posttransplant stages among MDS and AML patients. This review examines the application of HMAs as a bridge treatment to reduce the tumor burden and the determine appropriate dose during allo-HSCT. Within this review, we also examine the efficacy and safety of HMAs alone or HMA-based strategies in posttransplant settings for MDS and AML. Finally, we provide an overview of other epigenetic candidates, which have been discussed in the nontransplant setting.

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“…The three outcomes had moderate to high heterogeneity. Gao et al reported an an early death in induction related to mortality rates of 11.4% and 22.7% within 30 and 60 days, respectively [ 30 ].…”

Section: Resultsmentioning

confidence: 99%

“…Joshi et al and Schuler et al similarly observed that TP53 mutations were not associated with a poor prognosis in Ven-HMAs treatment [ 28 , 29 ]. However, the study by Gao et al found that TP53 mutations and relapse within 1 year of transplantation were independent risk factors for the outcome, while DNMT3A, NPM1, and IDH1/2 mutations may be associated with favorable CR/CRI rate [ 30 ]. It should be noted that the four studies were on a small scale and the prognostic impact of TP53 mutations still required observational studies based on large samples.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of venetoclax combined with hypomethylating agents for relapse of acute myeloid leukemia and myelodysplastic syndrome post allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis

Du,

Li,

Zhao

et al. 2023

BMC Cancer

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Background Currently, there is no standard treatment for managing relapse in patients with acute myeloid leukemia and myelodysplastic syndrome (AML/MDS) after allogeneic hematopoietic cell transplantation. Venetoclax-based therapies have been increasingly used for treating post-transplantation relapse of AML. The aim of this systematic review and meta-analysis was to evaluate the efficacy and adverse events of Venetoclax combined with hypomethylating agents (HMAs) for AML/MDS relapse post-transplantation. Methods We searched PubMed, Web of Science, Excerpta Medica Database, Cochrane Library, and Clinical. gov for eligible studies from the inception to February 2022. The Methodological Index for Non-Randomized Studies was used to evaluate the quality of the included literatures. The inverse variance method calculated the pooled proportion and 95% confidence interval (CI). Results This meta-analysis included 10 studies involving a total of 243 patients. The pooled complete response and complete response with incomplete blood count recovery rate of Venetoclax combined with HMAs for post-transplantation relapse in AML/MDS was 32% (95% CI, 26-39%, I2 = 0%), with an overall response rate of 48% (95% CI, 39-56%, I2 = 37%). The 6-month survival rate was 42% (95% CI, 29-55%, I2 = 62%) and the 1-year survival rate was 23% (95% CI, 11-38%, I2 = 78%). Conclusion This study demonstrated a moderate benefit of Venetoclax in combination with HMAs for patients with relapsed AML/MDS post-transplantation (including those who have received prior HMAs therapy), and may become one of treatment options in the future. Large-scale prospective studies are needed to confirm the potential benefit from venetoclax combined with HMAs.

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Venetoclax plus hypomethylating agent for the salvage treatment of relapsing myeloid malignancies after hematopoietic stem cell transplantation: A multicenter retrospective study on behalf of the Zhejiang Cooperative Group for Blood and Marrow Transplantation

Cited by 8 publications

References 8 publications

Optimization of Donor Lymphocyte Infusion for AML Relapse After Allo-HCT in the Era of New Drugs and Cell Engineering

Optimization of Donor Lymphocyte Infusion for AML Relapse After Allo-HCT in the Era of New Drugs and Cell Engineering

Generalist in allogeneic hematopoietic stem cell transplantation for MDS or AML: Epigenetic therapy

Efficacy and safety of venetoclax combined with hypomethylating agents for relapse of acute myeloid leukemia and myelodysplastic syndrome post allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis

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