Epidemiology: Non-Hodgkin’s Lymphoma. Increasing incidence over the past three decades but drivers of increase still unknown Country Coverage: the US, Japan, France, Germany, Italy, Spain, and the UK

Key findings Datamonitor Healthcare's key findings Epidemiology: Non-Hodgkin’s Lymphoma

Datamonitor Healthcare’s key findings Disease overview Non-Hodgkin's lymphoma (NHL) is a cancer that originates in lymphocytes, which are blood cells that form part of the immune system. NHL comprises a highly heterogeneous group of malignancies, displaying distinct behavioral, prognostic, and epidemiologic characteristics. NHL is slightly more predominant in developed countries where some 51% of global NHL cases occur. In 2008, there were approximately 356,000 NHL diagnoses across the globe. Incidence rates and historical trends of NHL are similar in the US and European markets, whereas Asian countries are known for a historically lower incidence. Incidence estimates In 2012, Datamonitor Healthcare estimates that 145,820 incident cases of NHL occurred in the US, Japan, and five major EU markets (France, Germany, Italy, Spain, and the UK). Of all the incident NHL cases in these markets, 71,300 (or 49%) were in the US, while approximately 58,610 occurred in the five major EU markets. The number of cases was similar across these markets and substantially lower than in the US – there were 10,780, 14,410, 15,440, 7,390, and 10,590 incident cases in France, Germany, Italy, Spain, and the UK, respectively. Epidemiologic drivers Risk factors for NHL are well established. These are immunodeficiency, infectious diseases (human T-cell lymphotropic virus, Epstein-Barr virus, Helicobacter pylori), obesity, tobacco smoking, and poor nutrition. However, contemporary epidemiologic trends have only been directly influenced by the advent of HIV/AIDS and, potentially, the rise of obesity in the Western population. Consequently, the rise in diagnosis of NHL is mainly attributable to increased awareness and improvements in diagnostic procedures. NHL subtype More than half of NHL cases are diffuse large B-cell and follicular lymphoma. Epidemiology: Non-Hodgkin’s Lymphoma 3

Disease overview Non-Hodgkin’s Lymphoma definition and ICD codes 4 Epidemiology: Non-Hodgkin’s Lymphoma 4

Non-Hodgkin’s lymphoma definition NHL is a cancer that originates in lymphocytes, which are blood cells that form part of the immune system. NHL comprises a highly heterogeneous group of malignancies, displaying distinct behavioral, prognostic, and epidemiologic characteristics. NHL is slightly more predominant in developed countries where some 51% of global NHL cases occur. There are several subtypes of NHL, with marked variation between them. Incidence rates vary by age and sex. Survival rates, risk factors, and treatment also vary by subtype. Some NHL subtypes can be aggressive, developing quickly. Others can be indolent, developing slowly and often not causing symptoms for many years. NHL classified in the International Classification of Diseases (ICD) as ICD code-9 200 and 202, and ICD code-10 C82–85 and C96 was included in this analysis. Sources: 1. WHO (1972) International Classification of Diseases and Related Health Problems ICD-9. 1,2 & 3 Revisions. 2nd edition WHO (2004) International Statistical Classification of Diseases and Related Health Problems ICD-10. 1,2 & 3 Revisions. 2nd edition. Epidemiology: Non-Hodgkin’s Lymphoma 5

Non-Hodgkin’s lymphoma forecast Epidemiologic forecast results Epidemiology: Non-Hodgkin’s Lymphoma 6

Non-Hodgkin’s lymphoma forecast Increase in patient populations across markets In 2012, Datamonitor Healthcare estimates that 145,820 incident cases of NHL occurred in the US, Japan, and five major EU markets. Of all the incident NHL cases in the US, Japan, and five major EU markets, 71,300 (or 49%) were in the US. In the same year, approximately 58,610 incident NHL cases occurred in the five major EU markets. There were 10,780, 14,410, 15,440, 7,390, and 10,590 incident cases in France, Germany, Italy, Spain, and the UK, respectively. In Japan, there were 15,910 incident cases of NHL in 2012. Between 2012 and 2030, incident NHL cases will increase by 41% in the US, Japan, and five major EU markets. The largest growth in incident cases over the forecast period will be in Italy (59%) followed by the US (48%). In Spain, NHL incident cases will grow by 40%, while growth over the period will be 34%, 29%, 25%, and 16% in the UK, France, Japan, and Germany, respectively. Epidemiology: Non-Hodgkin’s Lymphoma 7

NHL subtypes diagnosed in 2012 More than half of incident cases are diffuse large B-cell and follicular lymphoma Across these markets, approximately 85% of all NHL cases are B-cell lymphomas, with the majority being diffuse large B-cell and follicular lymphomas. Epidemiology: Non-Hodgkin’s Lymphoma 8

Conclusions and key takeaways . Epidemiology: Non-Hodgkin’s Lymphoma 9

Conclusions NHL incidence will continue to increase In the near future, NHL incidence will continue to increase across the US, Japan, and five major EU markets. The growth in incident cases is due to real increases in the diagnosis of NHL in these markets, as well as background population aging. NHL incidence is highest in older age groups, and as the populations age NHL diagnoses are also expected to rise. The increase in incident NHL cases projected in the US, Japan, and five major EU markets is in line with trends observed in the majority of developed countries. In these markets, the increase in NHL incidence is attributable to several factors including improvements in diagnostic techniques and data registration systems, such that the increase cannot be credited to any known risk factors. However, HIV is the only risk factor that is known to have changed over time, leading to an increase in the number of NHL cases among HIV-infected individuals. Epidemiology: Non-Hodgkin’s Lymphoma