Common medications in the risk and prognosis of lymphoid neoplasms and epidemiology of primary CNS lymphoma

Lymphoid neoplasms are malignancies arising from the lymphocyte, and include lymphoma subtypes, chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). It is a heterogenous group of diseases, with different molecular pathogenesis, clinical characteristics, treatments and outcome. There is increasing understanding that risk factors may differ between the subtypes.

The incidence of the non-Hodgkin subtypes of lymphoma (NHL) increased rapidly for several decades during the end of the 20th century, for mostly unknown reasons. Concurrently the use of many prophylactic medications such as statins and aspirin became common in Europe and North America. Anti-carcinogenic properties have been described in both these medications, but for statins there has also been concern about a potential conflicting effect of statins in lymphoma treatments that include the widely used monoclonal antibody rituximab.

In study I and II we investigated the association between statin use and disease-specific mortality in lymphoid neoplasms. We assessed statin exposure in 6-month periods before and after diagnosis of a lymphoid neoplasm in cohort studies, and at any time during follow-up in nested case-control studies. We assessed the dose-response relationship by categories of intensity of statin use (according to American College of Cardiology/American Heart Association guidelines as low, moderate and high intensity) and duration. In study I, we found that among patients with MM, statin use was associated with improved myeloma- specific mortality in all time-windows assessed. There was however no significant trend for dose intensity or duration. In study II, we found no association between statin use and lymphoma-specific survival in NHL overall or in CLL and other subtypes. We found improved lymphoma-specific survival in Burkitt lymphoma and in CLL patients that used statins for >2 years, but these findings could also be due to chance. We found no evidence of reduced efficacy of rituximab treatment for patients with statin use, which is reassuring.

In study III we used the American cohort the Nurses’ Health Study to assess detailed information on aspirin use over 25+ years and risk of NHL and its subtypes. We investigated both cumulative average quantity and duration of aspirin use. We found no association between aspirin use and risk of NHL overall, but there was an increased risk of follicular lymphoma for users of large quantities of aspirin (5+ tablets/week), as well as a significant trend across increasing categories of quantity.

In study IV we investigated the incidence of primary central nervous system lymphoma (PCNSL), a rare NHL subtype located in the CNS. PCNSL has traditionally had a dismal prognosis, but many new treatment schemes have been introduced lately. We found an increasing incidence primarily in the elderly (70+) that was consistent with an increasing trend of brain tumors of all types in the same age group, suggesting that this can, at least in part, be due to increased diagnostic procedures and reporting. We did not find any improvement in survival during the study period, indicating that the new treatments have not yet improved the prognosis in a population-based setting.

List of scientific papers

I. Elsa Brånvall, Sara Ekberg, Sandra Eloranta, Tove Wästerlid, Brenda M. Birmann, Karin E. Smedby. Statin use is associated with improved survival in multiple myeloma: A Swedish population-based study of 4315 patients. American Journal of Hematology. 2020 Jun;95(6):652-661.
https://doi.org/10.1002/ajh.25778

II. Elsa Brånvall, Sara Ekberg, Sandra Eloranta, Tove Wästerlid, Brenda M. Birmann, Karin E. Smedby. Statin use and survival in 16,098 patients with non-Hodgkin lymphoma or chronic lymphocytic leukemia in the rituximab era. [Manuscript]

III. Elsa Brånvall, Karin E. Smedby, Julie Batista, Bernard A. Rosner, Edward Giovannucci, Jan-Peter Glossmann, Kimberly A. Betrand, Honglei Chen, Francine Laden, Shumin Zhang, Brenda M. Birmann. Regular aspirin use and risk of non-Hodgkin lymphoma subtypes: A prospective analysis in the Nurses’ Health Study. [Manuscript]

IV. Sandra Eloranta, Elsa Brånvall, Fredrik Celsing, Karin Papworth, Maria Ljungkvist, Gunilla Enblad, Karin E. Smedby. Increasing incidence of primary central nervous system lymphoma but no improvement in survival Sweden 2000-2013. European Journal of Haematology. 2018 Jan;100(1):61-68.
https://doi.org/10.1111/ejh.12980