美国德克萨斯大学安德森癌症中心Courtney D. DiNardo团队分析了阿扎胞苷联合维奈托克治疗初治的急性髓细胞白血病的效果。2020年8月13日，该研究发表在《新英格兰医学杂志》上。

即使使用低甲基化剂治疗，老年急性髓细胞白血病（AML）患者的预后也很差。在此前的临床1b期研究中，阿扎胞苷联合维奈托克具有良好的疗效。

研究组招募了431例此前未接受过治疗的AML患者，这些患者存在基础共病，年龄超过75岁，因此不适宜标准的诱导疗法。将其随机分组，其中286名接受阿扎胞苷+维奈托克治疗，145名接受阿扎胞苷+安慰剂治疗。主要终点为总生存期。

两组患者的中位年龄均为76岁。中位随访20.5个月后，阿扎胞苷+维奈托克组的中位总生存期为14.7个月，显著长于对照组（9.6个月）。阿扎胞苷+维奈托克组的完全缓解率为36.7%，显著高于对照组（17.9％）；综合完全缓解率（完全缓解或血液学未完全恢复的完全缓解）为66.4％，亦显著高于对照组（28.3％）。

对关键不良事件进行分析，阿扎胞苷+维奈托克组和对照组中任意级别的恶心发生率分别为44％和35％，3级及以上血小板减少率分别为45％和38％，中性粒细胞减少率分别为42％和28％，发热性中性粒细胞减少率分别为42％和19％。阿扎胞苷+维奈托克组中有85％的患者发生了任意程度的感染，对照组中有67％，两组患者严重不良事件发生率分别为83％和73％。

研究结果表明，对于初治且不耐受强化疗方案的AML患者，使用阿扎胞苷+维奈托克治疗与仅阿扎胞苷相比，可显著延长患者的总生存期，提高缓解率。

附：英文原文

Title: Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia

Author: Courtney D. DiNardo, M.D.,, Brian A. Jonas, M.D., Ph.D.,, Vinod Pullarkat, M.D.,, Michael J. Thirman, M.D.,, Jacqueline S. Garcia, M.D.,, Andrew H. Wei, M.B., B.S., Ph.D.,, Marina Konopleva, M.D., Ph.D.,, Hartmut Dhner, M.D.,, Anthony Letai, M.D., Ph.D.,, Pierre Fenaux, M.D., Ph.D.,, Elizabeth Koller, M.D.,, Violaine Havelange, M.D., Ph.D.,, Brian Leber, M.D.,, Jordi Esteve, M.D., Ph.D.,, Jianxiang Wang, M.D.,, Vlatko Pejsa, M.D., Ph.D.,, Roman Hájek, M.D., Ph.D.,, Kimmo Porkka, M.D., Ph.D.,, árpád Illés, M.D., D.Sci.,, David Lavie, M.D.,, Roberto M. Lemoli, M.D.,, Kazuhito Yamamoto, M.D., Ph.D.,, Sung-Soo Yoon, M.D., Ph.D.,, Jun-Ho Jang, M.D.,, Su-Peng Yeh, M.D.,, Mehmet Turgut, M.D.,, Wan-Jen Hong, M.D.,, Ying Zhou, Ph.D.,, Jalaja Potluri, M.D.,, and Keith W. Pratz, M.D.

Issue&Volume: 2020-08-12

Abstract: Abstract

Background

Older patients with acute myeloid leukemia (AML) have a dismal prognosis, even after treatment with a hypomethylating agent. Azacitidine added to venetoclax had promising efficacy in a previous phase 1b study.

Methods

We randomly assigned previously untreated patients with confirmed AML who were ineligible for standard induction therapy because of coexisting conditions, because they were 75 years of age or older, or both to azacitidine plus either venetoclax or placebo. All patients received a standard dose of azacitidine (75 mg per square meter of body-surface area subcutaneously or intravenously on days 1 through 7 every 28-day cycle); venetoclax (target dose, 400 mg) or matching placebo was administered orally, once daily, in 28-day cycles. The primary end point was overall survival.

Results

The intention-to-treat population included 431 patients (286 in the azacitidine–venetoclax group and 145 in the azacitidine–placebo [control] group). The median age was 76 years in both groups (range, 49 to 91). At a median follow-up of 20.5 months, the median overall survival was 14.7 months in the azacitidine–venetoclax group and 9.6 months in the control group (hazard ratio for death, 0.66; 95% confidence interval, 0.52 to 0.85; P<0.001). The incidence of complete remission was higher with azacitidine–venetoclax than with the control regimen (36.7% vs. 17.9%; P<0.001), as was the composite complete remission (complete remission or complete remission with incomplete hematologic recovery) (66.4% vs. 28.3%; P<0.001). Key adverse events included nausea of any grade (in 44% of the patients in the azacitidine–venetoclax group and 35% of those in the control group) and grade 3 or higher thrombocytopenia (in 45% and 38%, respectively), neutropenia (in 42% and 28%), and febrile neutropenia (in 42% and 19%). Infections of any grade occurred in 85% of the patients in the azacitidine–venetoclax group and 67% of those in the control group, and serious adverse events occurred in 83% and 73%, respectively.

Conclusions

In previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone. The incidence of febrile neutropenia was higher in the venetoclax–azacitidine group than in the control group.

DOI: 10.1056/NEJMoa2012971

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2012971