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; Hong-Mei Yi; Xu-Feng Jiang; Qi Song; Yan Zhao; Yang He; Jian-Feng Li; Rong-Ji Mu; Hai Fang; Hao Yu; Hui Xiong; Biao Li; Sai-Juan Chen; Peng-Peng Xu; Wei-Li Zhao

doi:10.1016/j.ccell.2023.09.004

Genetic subtype-guided immunochemotherapy in diffuse large B cell lymphoma: The randomized GUIDANCE-01 trial

Cancer Cell. 2023 Oct 9;41(10):1705-1716.e5. doi: 10.1016/j.ccell.2023.09.004. Epub 2023 Sep 28.

Authors

Mu-Chen Zhang¹, Shuang Tian¹, Di Fu¹, Li Wang², Shu Cheng¹, Hong-Mei Yi³, Xu-Feng Jiang⁴, Qi Song⁵, Yan Zhao¹, Yang He¹, Jian-Feng Li¹, Rong-Ji Mu⁶, Hai Fang¹, Hao Yu⁷, Hui Xiong⁷, Biao Li⁴, Sai-Juan Chen¹, Peng-Peng Xu⁸, Wei-Li Zhao⁹

Affiliations

¹ 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.
² 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.
³ Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Department of Nuclear Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁶ Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁷ Department of Research and Development, Shanghai Righton Biotechnology Co. Ltd, Shanghai, China.
⁸ 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. Electronic address: pengpeng_xu@126.com.
⁹ 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. Electronic address: zhao.weili@yahoo.com.

PMID: 37774697
DOI: 10.1016/j.ccell.2023.09.004

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.

Keywords: diffuse large B cell lymphoma; genetic subtype; lymphoma microenvironment; randomized clinical trial; targeted therapy.