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. 2024 Dec 9:14:1465334.
doi: 10.3389/fonc.2024.1465334. eCollection 2024.

Efficacy and safety of hypomethylating agents in the treatment of AML/MDS patients relapsed post allogenetic hematopoietic stem cell transplantation

Yaxin Wang #  1 , Qingyun Wang #  1 , Hanyun Ren  1 , Yujun Dong  1 , Qingya Wang  1 , Zeyin Liang  1 , Yue Yin  1 , Wei Liu  1 , Weilin Xu  1 , Na Han  1 , Yuan Li  1
Affiliations

Efficacy and safety of hypomethylating agents in the treatment of AML/MDS patients relapsed post allogenetic hematopoietic stem cell transplantation

Yaxin Wang et al. Front Oncol. .

Abstract

Introduction: Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) constitute myeloid malignancies, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered as a potentially optimal approach for achieving a long term cure. However, post-allo-HSCT relapse remains a leading cause of mortality and therapeutic failure.

Methods: To evaluate the efficacy and safety of combining hypomethylating agents (HMAs) with Bcl-2 inhibitors in the treatment of AML/MDS relapse following allo-HSCT, we retrospectively collected data from 42 patients who experienced relapse between April 2012 and March 2022 at Peking University First Hospital. Among these patients, 21 underwent intensive chemotherapy (IC) alone, while the other 21 received treatment with HMAs after IC treatment, either alone or in combination with the Bcl-2 inhibitor venetoclax (VEN).

Results: The median overall survival (OS) was 9 ± 2.153 months, and the one-year OS rate was 41.5%. The overall response rate (ORR) in the chemotherapy group and the IC+HMAs ± VEN group was 52.38% (11/21) and 76.19% (16/21), respectively, with no significant difference found (P=0.107). Kaplan-Meier analysis revealed a significant difference in OS between the chemotherapy group and the IC+HMAs ± VEN group in our retrospective cohort study (P=0.041, χ2= 4.016). Additionally, a significant difference in overall survival (OS) rates was observed between the two groups for patients categorized as intermediate/high risk (P=0.008). The secondary relapse rate was 45.45% (5/11) in the IC cohort and 25% (4/16) in the IC+HMAs ± VEN group, respectively, with no significant difference identified between the two cohorts (P=0.268). Furthermore, upon assessing the risk of graft-versus-host disease (GvHD), infection, and agranulocytosis, no notable differences were observed with the use of HMAs, suggesting that HMAs did not increase the risk. In the IC+HMAs ± VEN group, 7 patients received VEN in addition to HMAs, and no significant statistical difference was found in OS when comparing patients who received HMAs alone and those who received HMA+VEN (P=0.183), also, a statistically significant difference in OS was noted between the two groups whenaccounting for competing risks (P=0.028).

Conclusions: This retrospective study highlights the efficacy of IC+HMAs ± VEN in treating AML/MDS patients experiencing relapse post allo-HSCT, improving survival rates, especially for those classified as intermediate/high risk, with favorable tolerability.

Keywords: allo-HSCT; hypomethylating agents; myeloid malignancy; relapse; venetoclax.

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Conflict of interest statement

The authors assert that the research was carried out without any commercial or financial relationships that could be perceived as a potential conflict of interest.

Figures

Figure 1
Figure 1
OS in IC group and IC+HMAs ± VEN group.
Figure 2
Figure 2
DFS in IC group and IC+HMAs ± VEN group.
Figure 3
Figure 3
OS in IC group and IC+HMAs ± VEN group with intermediate/high-risk prognosis patients.
Figure 4
Figure 4
OS in IC group and IC+HMAs ± VEN group under the competitive risk model.
Figure 5
Figure 5
secondary relapse in IC group and IC+HMAs ± VEN group.
Figure 6
Figure 6
aGvHD in two groups after DLI.
See this image and copyright information in PMC

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