弥漫性大B细胞淋巴瘤中基于基因亚型的免疫化疗：随机化GUIDANCE-01试验
Genetic subtype-guided immunochemotherapy in diffuse large B cell lymphoma: The randomized GUIDANCE-01 trial.
作者信息
Zhang Mu-Chen, Tian Shuang, Fu Di, Wang Li, Cheng Shu, Yi Hong-Mei, Jiang Xu-Feng, Song Qi, Zhao Yan, He Yang, Li Jian-Feng, Mu Rong-Ji, Fang Hai, Yu Hao, Xiong Hui, Li Biao, Chen Sai-Juan, Xu Peng-Peng, Zhao Wei-Li
机构信息
Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Pôle de Recherches Sino-Français en Science du Vivant et Génomique, Laboratory of Molecular Pathology, Shanghai, China.
出版信息
Cancer Cell. 2023 Oct 9;41(10):1705-1716.e5. doi: 10.1016/j.ccell.2023.09.004. Epub 2023 Sep 28.
We report the results of GUIDANCE-01 (NCT04025593), a randomized, phase II trial of R-CHOP alone or combined with targeted agents (R-CHOP-X) guided by genetic subtyping of newly diagnosed, intermediate-risk, or high-risk diffuse large B cell lymphoma (DLBCL). A total of 128 patients were randomized 1:1 to receive R-CHOP-X or R-CHOP. The study achieved the primary endpoint, showing significantly higher complete response rate with R-CHOP-X than R-CHOP (88% vs. 66%, p = 0.003), with overall response rate of 92% vs. 73% (p = 0.005). Two-year progression-free survival rates were 88% vs. 63% (p < 0.001), and 2-year overall survival rates were 94% vs. 77% (p = 0.001). Meanwhile, post hoc RNA-sequencing validated our simplified genetic subtyping algorithm and previously established lymphoma microenvironment subtypes. Our findings highlight the efficacy and safety of R-CHOP-X, a mechanism-based tailored therapy, which dually targeted genetic and microenvironmental alterations in patients with newly diagnosed DLBCL.
我们报告了GUIDANCE-01（NCT04025593）试验的结果，这是一项随机II期试验，针对新诊断的中危或高危弥漫性大B细胞淋巴瘤（DLBCL）患者，比较单纯R-CHOP方案与联合靶向药物（R-CHOP-X）方案的疗效。共128例患者按1:1随机分组，分别接受R-CHOP-X或R-CHOP方案治疗。该研究达到了主要终点，结果显示R-CHOP-X方案的完全缓解率显著高于R-CHOP方案（88%对66%，p = 0.003），总体缓解率分别为92%和73%（p = 0.005）。两年无进展生存率分别为88%和63%（p < 0.001），两年总生存率分别为94%和77%（p = 0.001）。同时，事后RNA测序验证了我们简化的基因分型算法以及先前建立的淋巴瘤微环境亚型。我们的研究结果突出了R-CHOP-X这种基于机制的个体化疗法在新诊断DLBCL患者中的疗效和安全性，该疗法同时针对基因和微环境改变。
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