We sought to understand the clinical course and molecular phenotype of patients who showed disease progression after programmed cell death ligand 1 (PD-L1) inhibitor treatment but subsequently responded to PD-1 inhibitor treatment. We also explored the response to PD-1-axis targeted therapy of classical Hodgkin lymphoma (cHL) according to genetically driven PD-L1 and programmed cell death ligand 2 (PD-L2) expression. | Chen et al. BMC Cancer 2022 22 9 https s12885-021-09028-4 RESEARCH Open Access High efficacy of PD-1 inhibitor after initial failure of PD-L1 inhibitor in Relapsed Refractory classical Hodgkin Lymphoma Xi Chen1 2 Haiying Kong3 Linxiang Luo4 Shuiyun Han1 2 Tao Lei1 2 Haifeng Yu1 2 Na Guo2 5 Cong Li1 2 Shuailing Peng1 2 Xiaowu Dong6 Haiyan Yang1 2 and Meijuan Wu2 5 Abstract Purpose We sought to understand the clinical course and molecular phenotype of patients who showed disease progression after programmed cell death ligand 1 PD-L1 inhibitor treatment but subsequently responded to PD-1 inhibitor treatment. We also explored the response to PD-1-axis targeted therapy of classical Hodgkin lymphoma cHL according to genetically driven PD-L1 and programmed cell death ligand 2 PD-L2 expression. Methods Five patients in a phase II clinical trial of CS1001 PD-L1 inhibitor for relapsed or refractory R R cHL were retrospectively reviewed. Formalin-fixed paraffin-embedded whole tissues from the five patients were evaluated for genetic alterations based on FISH and the expression of PD-L1 PD-L2 PD-1 major histocompatibility complex MHC class I II and the tumor microenvironment factorsCD163 and FOXP3 in the microenvironmental niche as revealed by multiplex immunofluorescence. Results All five patients showed primary refractory disease during first-line treatment. Four patients received PD-1 inhibitor after dropping out of the clinical trial and all demonstrated at least a partial response. The progression-free survival ranged from 7 to 28 months median 18 months and amplification was observed in all five patients at the PD-L1 PD-L2 locus. PD-L1 and PD-L2 were colocalized on Hodgkin Reed-Sternberg HRS cells in four of the five 80 patients. There was differential expression of PD-L1 and PD-L2 in cells in the tumor microenvironment in cHL especially in HRS cells background cells and tumor-associated macrophages. Conclusions PD-L1 monotherapy may not be
