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. 2023 Mar 23:13:1137175.
doi: 10.3389/fonc.2023.1137175. eCollection 2023.

Venetoclax plus hypomethylating agents versus intensive chemotherapy for hematological relapse of myeloid malignancies after allo-HSCT

Zhangjie Chen  1   2 , Sisi Zhen  1   2 , Tingting Zhang  1   2 , Yuyan Shen  1   2 , Aiming Pang  1   2 , Donglin Yang  1   2 , Rongli Zhang  1   2 , Qiaoling Ma  1   2 , Yi He  1   2 , Jialin Wei  1   2 , Weihua Zhai  1   2 , Xin Chen  1   2 , Erlie Jiang  1   2 , Mingzhe Han  1   2 , Sizhou Feng  1   2
Affiliations

Venetoclax plus hypomethylating agents versus intensive chemotherapy for hematological relapse of myeloid malignancies after allo-HSCT

Zhangjie Chen et al. Front Oncol. .

Abstract

Introduction: Since allogeneic stem cell transplantation (allo-HSCT) is considered one of the curative treatments for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), hematological relapse following allo-HSCT remained a crucial concern for patients' survival.

Methods: We retrospectively compared patients who received venetoclax plus hypomethylating agents (VEN+HMA, n=23) or intensive chemotherapy (IC, n=42) for hematological relapse of myeloid malignancies after allo-HSCT. HMA selection included decitabine (n=2) and azacitidine (n=21), and combined donor lymphocyte infusion was administered to 21 and 42 patients in VEN+HMA and IC groups, respectively.

Results: Median age of all patients was 39 (16-64) years old. Overall response rates, including complete response (CR), CR with incomplete recovery of normal neutrophil or platelet counts (CRi) and partial response (PR), were not significantly different between VEN+HMA and IC groups (60.1% versus 64.3%, P=0.785). CR/CRi rate was 52.2% in VEN+HMA and 59.5% in IC group (P=0.567). The rate of relapse after response was 66.7% in VEN+HMA group and 40.7% in IC group (P=0.176). Median overall survival was 209.0 (95%CI 130.9-287.1) days for VEN+HMA group versus 211.0 (95%CI 28.7-393.3) days for IC group (P=0.491). The incidence of lung infection (17.4% versus 50.0%, P=0.010), thrombocytopenia (73.9% versus 95.2%, P=0.035) and acute graft-versus-host disease (aGvHD) (50.0% versus 13.0%, P=0.003) was significantly higher in IC group.

Discussion: In conclusion, VEN+HMA is not inferior to IC regimen in terms of improving response and survival, and is associated with a lower incidence of adverse events and aGvHD. However, further research is required to enhance long-term survival.

Keywords: acute myeloid leukemia; allo-HSCT; myeloid malignancy; relapse; venetoclax.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Survival analysis of all patients. Overall survival of patients achieving CR/CRi versus non-CR/CRi (A), MRD negativity versus MRD positivity (B) and receiving venetoclax-based treatment vs. IC treatment (C). VEN, venetoclax; HMA, hypomethylating agent; IC intensive chemotherapy.
Figure 2
Figure 2
Subgroup analysis of survival VEN, venetoclax; HMA hypomethylating agent; IC, intensive chemotherapy; ELN, European leukemia network; DLI, donor lymphocyte infusion; GvHD, graft-versus-host disease; aGvHD, acute graft-versus-host disease; allo-HSCT, allogeneic hematopoietic stem cell transplantation; BM, bone marrow; WBC, white blood cell; HgB, hemoglobin; PLT, platelet.
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