Genomic risk factors for central nervous system relapse in patients with diffuse large B-cell lymphoma

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PURPOSE: Central nervous system (CNS) relapse is associated with poor survival, and remains an unmet challenge in patients with diffuse large B-cell lymphoma (DLBCL). Identifying patients at high risk of CNS relapse and offering prophylactic treatment could improve patient prognosis. METHODS: Here, we studied 234 patients with DLBCL using open patient-level clinical and sequencing data to explore risk factors for CNS relapse. Patients were divided into Cohort A (CNS involvement at baseline), Cohort B (CNS recurrence), and Cohort C (patients without secondary CNS involvement and with a follow-up interval > 3 years). We investigated the risk factors for CNS relapse in Cohorts B + C. RESULTS: Genetic alterations with statistical significance, determined by univariate analysis, and an incidence rate ≥ 5%, together with clinical factors, correlated with CNS relapse risk in a multivariate analysis. Multivariate logistic regression analysis revealed that concomitant MYD88 L265P and CDKN2A loss (p = 0.012), TET2 mutation (p = 0.037), ARID1A mutation (p = 0.010), and INO80 (p = 0.002) were independently correlated with a high risk of CNS relapse after adjusting for the IPI risk groups, B symptom and cell of origin (COO). The classifier that integrated genomic risk factors was superior in predicting CNS relapse (area under the receiver operating characteristic curve [AUROC]: 0.91) compared with the IPI (AUROC: 0.77, p < 0.001) or IPI in combination with COO classifiers (AUROC: 0.81, p = 0.013). CONCLUSION: This study identified several genomic alterations as risk factors for CNS relapse.