Genetic subtype-guided immunochemotherapy in diffuse large B cell lymphoma: The randomized GUIDANCE-01 trial
Mu‐Chen Zhang, Shuang Tian, Di Fu, Li Wang, Shu Cheng, Hongmei Yi, Xufeng Jiang, Qi Song, Yan Zhao, Yang He, Jianfeng Li, Rongji Mu, Hai Fang, Hao Yu, Hui Xiong, Biao Li, Sai‐Juan Chen, Pengpeng Xu, Weili Zhao
Abstract
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.