Supplementary Material for: Limited efficacy of Venetoclax Combination Regimens in Acute Myeloid Leukemia with Extramedullary Relapse

The recently approved Bcl-2 inhibitor venetoclax (VEN) has achieved promising outcomes in new and relapsed/refractory (R/R) acute myeloid leukemia (AML). Although its use is not well-established in R/R AML with extramedullary disease (EMD), some reports have shown promising outcomes. We retrospectively analyzed 11 patients of R/R AML with EMD [with (n=4) or without (n=7) concurrent marrow involvement], who were treated with VEN plus decitabine (n=9) or low-dose cytarabine (n=2) between May 2020 and October 2020 in Seoul St. Mary’s Hospital. The median number of prior treatment lines was 3 (1-6) and most (n=9, 81.8%) had multiple sites of EMD. Nine patients (81.8%) received concurrent therapy for EM involvement sites with radiotherapy (RT) (n=4), surgery (n=1) and both of them (n=4). Among 11 patients, four patients (36.4%) had either marrow or EM responses to VEN-combination; EM response was seen in one patient (9.1%, partial response) who had received concurrent radiotherapy (25Gy, 10fx) during 1st cycle of VEN-combination, and other three patients showed marrow response without EM response. After median follow-up of 27.0 months, the median overall survival was estimated to be 5.4 months. To conclude, VEN-combination regimens have shown only modest efficacy in EM recurrence of AML with little impact on eliciting EM response.

近日获批的Bcl-2抑制剂（Bcl-2 inhibitor）维奈克拉（venetoclax，VEN）在初治及复发/难治性（R/R）急性髓系白血病（AML）中已取得良好疗效。尽管其在合并髓外病变（EMD）的R/R AML中的应用尚未明确，但已有部分研究报告显示出积极的治疗效果。本研究回顾性分析了2020年5月至2020年10月期间，首尔圣母医院收治的11例合并EMD的R/R AML患者（其中4例同时合并骨髓受累，7例未合并骨髓受累），所有患者均接受维奈克拉联合治疗：9例采用维奈克拉联合地西他滨方案，2例采用维奈克拉联合低剂量阿糖胞苷方案。
该队列患者的既往治疗线数中位数为3（范围1~6），其中多数（9例，占比81.8%）存在多部位髓外病变。9例患者（81.8%）针对髓外病变接受了同步治疗，包括放射治疗（RT）4例、手术治疗1例、放射治疗联合手术治疗4例。
11例患者中，4例（36.4%）在维奈克拉联合治疗后获得骨髓或髓外病变应答；其中仅1例患者（9.1%，部分缓解）在第1周期维奈克拉联合治疗期间接受了同步放射治疗（总剂量25Gy，分10次照射）后获得髓外病变应答，其余3例患者仅获得骨髓应答，未出现髓外病变应答。
经中位随访27.0个月后，该队列的中位总生存期估算为5.4个月。综上，维奈克拉联合方案在AML髓外复发中仅展现出中等疗效，对诱导髓外病变应答的作用有限。