Time to treatment is an independent prognostic factor in aggressive non-Hodgkin lymphomas

In aggressive lymphomas, discrepancies in survival reported from experimental and observational studies may reflect selective non-enrolment of high-risk patients in trials. We examined the association between time from diagnosis to chemotherapy and overall survival in diffuse large B-cell (DLBCL), Burkitt (BL), mantle cell (MCL) and peripheral T-cell lymphoma (PTCL), using National Cancer Data Base records of 130 549 patients treated in 2004-2014. Across the histologies, patients who started chemotherapy within 7 days of diagnosis had more often high International Prognostic Index (IPI) or advanced-stage disease. The discrepancy in 3-year survival between groups treated within 7 or >30 days from diagnosis ranged from 14% in BL to 30% in MCL. After adjusting for the IPI, time to treatment was significantly associated with shorter overall survival. Using the group treated >30 days from diagnosis as reference, patients treated within 7 days had a hazard ratio of 1·38 [95% confidence interval (CI), 1·28-1·48] in DLBCL, 1·42 (95% CI, 1·22-1·66) in BL, 2·23 (95% CI, 1·79-2·78) in MCL and 1·46 (95% CI, 1·18-1·81) in PTCL. Time from diagnosis to treatment may reflect high-risk features uncaptured by standard prognostic assessments. Clinical trials should accommodate patients who need urgent therapy to improve external validity and detect treatment effects in high-risk groups.