Shorter Diagnosis-to-Treatment Interval in Diffuse Large B-Cell Lymphoma is Associated With Inferior Overall Survival in a Large, Population-Based Registry.

BACKGROUND: Because of prolonged screening requirements, patient and time-dependent selection have been proposed as potential biases in clinical trials. The screening process may exclude patients with a need for emergent treatment (and a short period from diagnosis to treatment initiation [DTI]). We explored the impact of DTI on overall survival (OS) in a population-based cohort of patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: Using population-based administrative databases in Ontario, Canada, we identified adults aged ≥18 years with DLBCL treated with rituximab-based chemotherapy for curative intent between January 2005 and December 2015. Cox regression and multivariable analyses were presented to evaluate the impact of time from DTI on OS, controlling for relevant covariates. RESULTS: We identified 9,441 patients with DLBCL in Ontario; median age was 66 years, 53.6% were male, median number of comorbidities (Johns Hopkins aggregated diagnosis groups) was 10 (interquartile range [IQR], 8-13), and median DTI was 37 days (IQR, 22-61). Between treatment initiation and study end, 43% of patients died (median OS, 1 year; IQR, 0.4-2.8 years). Shorter DTI was a significant predictor of mortality (P<.001). Compared with the shortest DTI period of 0-18 days, those who commenced therapy at 19-29 days (hazard ratio [HR], 0.75; 95% CI, 0.68-0.84), 30-41 days (HR, 0.70; 95% CI, 0.63-0.78), 42-57 days (HR, 0.52; 95% CI, 0.46-0.58), and 58-180 days (HR, 0.52; 95% CI, 0.47-0.58) had improved survival. Increasing age (HR, 1.03; 95% CI, 1.03-1.04), male sex (HR, 1.23; 95% CI, 1.14-1.32), and increasing number of comorbidities (HR, 1.12; 95% CI, 1.11-1.13) were associated with inferior survival. CONCLUSIONS: Among patients with DLBCL, shorter DTI was associated with inferior OS. Therefore, DTI may represent a surrogate marker for aggressive biology. Clinical trials with lengthy screening periods are likely creating a time-dependent patient selection bias.

Statin and cyclooxygenase-2 inhibitors improve survival in newly diagnosed diffuse large B-cell lymphoma: a large population-based study of 4913 subjects.

Preclinical data suggests anti-lymphoma potential for statins, metformin and cyclooxygenase-2 (COX-2) inhibitors. We performed a retrospective population-based study of all adults aged ≥66 years diagnosed with diffuse large B-cell lymphoma (DLBCL) or transformed lymphoma treated with a rituximab containing regimen, between 2005 and 2015 in Ontario, Canada. Using administrative databases, we assessed the impact of medication exposures, prior to chemo-immunotherapy, on lymphoma survival. Cox regression analyses, controlling for sociodemographic factors and comorbidities, examined the relationship between medication exposure and survival. In total, 4913 patients were treated with curative intent (median age 75 years, 51% male) and 52·2% died at a median of 1 year from treatment initiation (67% due to DLBCL). In the year prior to commencing treatment, 45·7% received statins, 16·3% metformin, and 25·0% a COX-2 inhibitor. Adjusting for confounders, exposure to statin and COX-2 inhibitors prior to chemo-immunotherapy independently conferred a survival advantage: statin exposure for 30 days (hazard ratio [HR] 0·97, 95% confidence interval [CI] 0·96-0·98), 180 days (HR 0·84, 95% CI 0·80-0·89) and 365 days (HR 0·71, 95% CI 0·63-0·79) and COX-2 inhibitor exposure for 30 days (HR 0·95, 95% CI 0·95-0·98), 180 days (HR 0·76, 95% CI 0·66-0·86) and 365 days (HR 0·57, 95% CI 0·43-0·74). Metformin had no significant impact. This population-based study found a dose-related survival benefit of exposure to statins and COX-2 inhibitors prior to chemo-immunotherapy for newly diagnosed DLBCL.