Causes of excess non-lymphoma death in 58,000 patients with DLBCL diagnosed during 1997-2020 and followed for up to 25 years

Survival from diffuse large B-cell lymphoma (DLBCL) has improved, raising interest in mortality from non-lymphoma causes in DLBCL patients, which is known to be increased compared with the general population. This study investigates excess mortality after DLBCL, quantifying both the absolute magnitude of the total non-lymphoma excess and the contributions of major disease groups. 58,221 patients aged 18-79 diagnosed with DLBCL as their first lymphoma in England during 1997-2020 were identified from the National Cancer Registration and Analysis Service and followed for up to 25 years (median 10.2 years). Absolute excess mortality rates (AERs) and standardized mortality ratios (SMRs) were estimated. A total of 30,596 patients died, 35.6% from lymphoma and 17.0% from other causes. The non-lymphoma mortality rate was 58% higher than that of the general population (SMR=1.58, 95% confidence interval 1.55-1.61), with over 100 excess non-lymphoma deaths per 10,000 person-years (AER=103.8, 98.2-109.4). The non-lymphoma AER was substantial during the first year after diagnosis (AER=369.1, 349.1-389.7). It subsequently fell, but remained significantly elevated throughout follow-up, even beyond 10 years (AER=93.7, 80.5-107.3). Disease groups with the biggest contributions to the AER were: infection <1 year after diagnosis, constituting 29%; hematological causes excluding lymphoma (e.g., leukemia) during years 1-4, 38%; and solid tumors thereafter, 31% in years 5-9 and 34% in years 10-25. Deaths from circulatory disease were elevated overall, but the SMR diminished in more recent calendar years of diagnosis. These insights may help guide treatment developments, interventions, and screening strategies towards reducing excess non-lymphoma deaths in the future.