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

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Abstract
Survival in diffuse large B-cell lymphoma (DLBCL) has improved, raising interest in mortality from nonlymphoma causes in patients with DLBCL, which is known to be increased compared with the general population. We investigate excess mortality after DLBCL, quantifying both the absolute magnitude of the total nonlymphoma excess and the contributions of major disease groups. All 58 221 patients aged 18 to 79 years diagnosed with DLBCL as their first lymphoma in England during 1997 to 2020 were identified 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 nonlymphoma mortality rate was 58% higher than that of the general population (SMR, 1.58; 95% confidence interval [CI], 1.55-1.61), with >100 excess nonlymphoma deaths per 10 000 person-years (AER, 103.8; 95% CI, 98.2-109.4). The nonlymphoma AER was substantial during the first year after diagnosis (AER, 369.1; 95% CI, 349.1-389.7). It subsequently fell but remained significantly elevated throughout follow-up, even beyond 10 years (AER, 93.7; 95% CI, 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 (eg, leukemia) during years 1 to 4, 38%; and solid tumors thereafter, 31% in years 5 to 9 and 34% in years 10 to 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 toward reducing excess nonlymphoma deaths in the future.

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