TP53 Mutation Is the Only Robust Mutational Biomarker for Outcome Found in a Consecutive Clinical Cohort of Real‐Word Patients With Primary Large B‐Cell Lymphoma

Introduction: Large B-cell lymphoma (LBCL) taxonomy has moved in the direction of a molecular classification, but further clinical experience is needed. We present high-risk gene mutations, which predict outcome in an exploratory study of a consecutive real-world cohort of patients with primary LBCL treated with R-CHOP or R-CHOP-like therapy. Methods: The study was a Registry Study Research Project. Sixty-one patients with LBCL, who had a diagnostic tumor sample successfully examined with a 59-gene next-generation sequencing (NGS) panel as a part of routine clinical work, were included in an otherwise unselected cohort. Data were extracted from patient files and pathology reports. Results: Mutations in NOTCH2 (HR 9.69; 95% CI [2.46–38.11]; p = 0.0012), PRDM1 (HR 3.54; 95% CI [1.03–12.22]; p = 0.045), and TP53 (HR 5.89; 95% CI [1.71–20.32]; p = 0.005) were significantly associated with inferior survival in patients with primary LBCL treated with intention to cure with at least three series of R-CHOP or R-CHOP-like therapy. Neither MYD88 (HR 0.66; 95% CI (0.17–2.49), p = 0.54) nor CD79B (HR 0.84;95% CI (0.18–3.88), p = 0.82) mutations were associated with inferior survival. Conclusion: With a targeted gene panel and NGS methodology feasible in daily diagnostic routine, we identified high-risk gene mutations with a significant prognostic impact of which TP53 mutations were reproducible across validation cohorts.