Service d'Hématologie et Thérapie Cellulaire, Centre Hospitalier Universitaire de Tours, Hôpital Bretonneau, Bâtiment Kaplan, 2, boulevard Tonnellé, 37044, Tours Cedex 09, France.
ERL CNRS 7001, Leukemic Niche and Redox Metabolism (LNOx), Faculté de Médecine, Université de Tours, Tours, France.
Sci Rep. 2022 Jun 13;12(1):9748. doi: 10.1038/s41598-022-13626-y.
The treatment of acute myeloid leukemia (AML) with unfavorable cytogenetics treatment remains a challenge. We previously established that ex vivo exposure of AML blasts to eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or fish oil emulsion (FO) induces Nrf2 pathway activation, metabolic switch, and cell death. The FILO group launched a pilot clinical study to evaluate the feasibility, safety, and efficacy of the adjunction of a commercial FO emulsion to 3 + 7 in untreated AML with unfavorable cytogenetics. The primary objective was complete response (CR). Thirty patients were included. FO administration raised the plasma levels of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids (p < 0.001). The pharmacokinetics of cytarabine and daunorubicin were unaffected. A historical comparison to the LAM2001 trial (Lioure et al. Blood 2012) found a higher frequency of grade 3 serious adverse events, with no drug-related unexpected toxicity. The CR rate was 77%, and the partial response (PR) 10%, not significantly superior to that of the previous study (CR 72%, PR 1%). RT-qPCR analysis of Nrf2 target genes and antioxidant enzymes did not show a significant in vivo response. Overall, FO emulsion adjunction to 3 + 7 is feasible. An improvement in CR was not shown in this cohort of high-risk patients. The present data does not support the use of FO in adjunction with 3 + 7 in high-risk AML patients.ClinicalTrials.gov identifier: NCT01999413.
采用不利细胞遗传学治疗急性髓系白血病 (AML) 仍然是一个挑战。我们之前已经证实，体外将 EPA、DHA 或鱼油乳剂暴露于 AML 原始细胞中可诱导 Nrf2 通路激活、代谢转换和细胞死亡。FILO 组开展了一项临床试验，旨在评估在具有不利细胞遗传学的未治疗 AML 患者中添加商业鱼油乳剂对 3+7 方案的可行性、安全性和疗效。主要终点为完全缓解 (CR)。共纳入 30 例患者。FO 给药可升高血浆 EPA 和 DHA 水平（p<0.001）。阿糖胞苷和柔红霉素的药代动力学不受影响。与 LAM2001 试验（Lioure 等人，Blood 2012）的历史比较发现，3 级严重不良事件发生率更高，但无药物相关意外毒性。CR 率为 77%，部分缓解（PR）为 10%，与既往研究（CR 为 72%，PR 为 1%）相比无显著优势。Nrf2 靶基因和抗氧化酶的 RT-qPCR 分析未显示出明显的体内反应。总之，3+7 方案添加 FO 乳剂是可行的。在这组高危患者中，CR 并未改善。目前的数据不支持在高危 AML 患者中添加 3+7 方案时使用 FO。临床试验编号：NCT01999413。
