Trends in non-Hodgkin lymphoma mortality rate in Japan and the United States: A population-based study

Characterizing trends in mortality rates with consideration of trends in incidence rates at the population level could help identify unmet needs in public health and provide essential indicators of cancer control. In the late 20th century, the arrival of the first molecular targeted agent, rituximab, for non-Hodgkin lymphoma (NHL) led to a paradigm shift in NHL treatment. However, the public health impact of this arrival has not been fully clarified. Here, we evaluated trends in the mortality and incidence rates of NHL in Japan and the United States. Age-standardized rates of mortality reversed after the introduction of rituximab, around 2000, beginning to decline significantly with annual percent changes (95% confidence interval) of -2.6% (-3.6% to -1.6%) in Japan and - 3.9% (-4.2% to -3.5%) in the United States. Despite an increase in incidence, the mortality in all age groups weakened the upward trends or decreased in both countries. From a long-term perspective, the trends in mortality rates differed between the countries. In the United States, the mortality rate has declined continuously since the introduction of rituximab, with a declining incidence rate. In contrast, in Japan, the mortality rate stopped declining and the incidence rate increased remarkably. The introduction of rituximab has had a substantial impact at the population level across a wide range of individuals. To reduce the disease burden in terms of mortality, elucidating risk factors that lead to a decreasing incidence rate is warranted for NHL, as well as further development of novel treatments.