The Association Between Biologic Exposure and Diagnosis of Lymphoma, A Case Series and Review of the Literature.


Flood R, Mullan R, Kane D, Enright H, McHugh J, Desmond R.


Department of Haematology and Rheumatology, Tallaght University Hospital.


In the modern era the routine use of biologic agents in the treatment of inflammatory diseases has been an important medical advancement, with great outcomes and improvement in quality of life for patients. However these medicines are associated with rare but serious adverse events. The question of an association between use of biologics and the development of lymphoma has been suggested. Here we review a series of eight patients from The Adelaide and Meath Hospital, Tallaght (AMNCH) that developed lymphomas post immunosuppressive therapy.


We conducted a review of the literature on the association of biologic therapy and development of lymphomas.


A list was compiled of patients who had attended the haematology department in AMNCH for treatment of lymphomas with a history of biologic drug exposure (Tumour necrosis factor inhibitors (Anti-TNF), Interleukin-6 inhibitors (IL-6) etc). A chart review and brief outline of each case was completed. The PubMed database was searched for articles regarding biologic agents and lymphomas and the relevant papers reviewed.


Clinical detail of seven patients that underwent treatment for lymphoma with prior biologic exposure in the AMNCH catchment area was available. In the case series four had a diagnosis of rheumatoid arthritis (RA) one ankylosing spondylitis, one crohns and one hydradenitis suppurativa. Five had previously been treated with adalimumab, two with etanercept and one with golimumab. Four of the patients went on to develop diffuse large B cell lymphoma (DLBCL), two Hodgkins Lymphoma, one large T cell granular lymphocytosis. The overwhelming evidence from the literature review, including a Cochrane review of 163 RCTs with 50,010 participants and 46 extension studies with 11,954 participants states that although biologic therapy is associated with adverse effects there is no link between their use and development of lymphoma. Indeed the pathophysiology of inflammatory conditions such as RA, crohns etc predisposes to malignancy.


Our case series details information on seven patients that developed different subtypes of lymphoma post biologic therapy. On review of the literature to date there is no evidence that biologics cause lymphoma, rather inflammatory activity. These are relatively new medications and long term data and registries are required.