Intensive chemotherapy after hypomethylating agent and venetoclax in adult acute myeloid leukemia

Blood Neoplasia Pub Date : 2024-08-28 DOI:10.1016/j.bneo.2024.100038

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Abstract

The combination of a hypomethylating agent (HMA) and venetoclax (VEN) is approved for adults aged >75 years with newly diagnosed acute myeloid leukemia (AML) as well as those ineligible for intensive chemotherapy (IC). HMA/VEN is increasingly substituted for IC in adults with AML aged <75 years, particularly in those with adverse cytogenetic and molecular features. When patients fail to respond or relapse after HMA/VEN, the utility of salvage IC is largely unknown. We performed a retrospective single-institution study and identified 46 patients who received IC after HMA/VEN, including 24 patients who received HMA/VEN as their first treatment for AML. This population had complete remission (CR)/CR with incomplete count recovery (CRi)/morphologic leukemia-free state rate of 37%, CR/CRi rate of 28%, and a median overall survival (mOS) of 7.2 months (95% confidence interval, 5.0-10.3). Patients who relapsed after an initial response to HMA/VEN and subsequently received IC were more likely to achieve a CR/CRi than those refractory to HMA/VEN (50% vs 19%; P = .04), although there was no statistically significant difference in survival (mOS, 8.8 vs 5.4 months; P = .64). Age >65 years predicted poorer survival (mOS, 4.3 vs 10.6 months; P < .001). IC after HMA/VEN should be further studied and chosen with caution.

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成人急性髓性白血病患者使用低甲基化药物和 Venetoclax 后的强化化疗

摘要低甲基化药物（HMA）和 Venetoclax（VEN）的联合用药已被批准用于年龄为 75 岁的新诊断急性髓性白血病（AML）成人患者以及不符合强化化疗（IC）条件的患者。在 75 岁的成人急性髓细胞白血病患者中，HMA/VEN 越来越多地取代 IC，尤其是那些细胞遗传学和分子特征不良的患者。当患者接受HMA/VEN治疗后无反应或复发时，挽救性IC的效用在很大程度上还不得而知。我们进行了一项单机构回顾性研究，确定了 46 名在 HMA/VEN 后接受 IC 治疗的患者，其中包括 24 名首次接受 HMA/VEN 治疗的急性髓细胞性白血病患者。这些患者的完全缓解（CR）/CR伴不完全计数恢复（CRi）/无形态白血病状态率为37%，CR/CRi率为28%，中位总生存期（mOS）为7.2个月（95%置信区间，5.0-10.3）。与HMA/VEN难治性患者相比，HMA/VEN初始反应后复发并随后接受IC治疗的患者更有可能获得CR/CRi（50% vs 19%；P = .04），但生存期（mOS，8.8个月 vs 5.4个月；P = .64）没有显著统计学差异。65岁的患者生存率较低（mOS，4.3 个月 vs 10.6 个月；P = .001）。应进一步研究 HMA/VEN 后的 IC，并谨慎选择。

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Blood Neoplasia

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