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Summary  Mutations in  SOCS1  are frequent in primary mediastinal B‐cell lymphoma and classical Hodgkin lymphoma. In the latter,  SOCS1  mutations affect the length of the encoded protein (major mutations) and are associated with shorter patient survival. Two independent studies examined the prognostic impact of  SOCS1  mutations in diffuse large B‐cell lymphoma (DLBCL) and showed differing results. This may be due to the small number of included patients, the heterogeneity of patients’ demographics and the distinct treatment schemes in these studies. To overcome the size limitations of these previous studies, we assessed  SOCS1  mutations in the RICOVER‐60 cohort. The cohort uniformly consists of elderly patients (aged 61–80 years) treated with the CHOP‐14 scheme (cyclophosphamide, hydroxydaunorubicin, vincristine, prednisolone at 14‐day intervals) with or without an additional rituximab treatment. Patient outcomes were analysed with regard to overall  SOCS1  mutation frequency, major and minor mutations and a novel impact‐based classifier – against the treatment modalities. Patients harbouring putative pathogenic  SOCS1  mutations showed significant reduced overall survival within the CHOP plus rituximab group. Hence, putative pathogenic  SOCS1  mutations seem to efface the beneficial effect of the therapeutic CD20 antibody. Comparing published data of whole exome and transcriptome sequencing of a large DLBCL cohort confirmed that predicted deleterious  SOCS1  mutations forecast pre‐eminent survival in early onset DLBCL.

The impact of SOCS1 mutations in diffuse large B‐cell lymphoma