Spectrum of lymphomas across different drug treatment groups in rheumatoid arthritis: a European registries collaborative project

Abstract

BackgroundLymphomas comprise a heterogeneous group of malignant diseases with highly variable prognosis. Rheumatoid arthritis (RA) is associated with a twofold increased risk of both Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). It is unknown whether treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) affect the risk of specific lymphoma subtypes.MethodsPatients never exposed to (bionaïve) or ever treated with bDMARDs from 12 European biologic registers were followed prospectively for the occurrence of first ever histologically confirmed lymphoma. Patients were considered exposed to a bDMARD after having received the first dose. Lymphomas were attributed to the most recently received bDMARD.ResultsAmong 124 997 patients (mean age 59 years; 73.7% female), 533 lymphomas were reported. Of these, 9.5% were HL, 83.8% B-cell NHL and 6.8% T-cell NHL. No cases of hepatosplenic T-cell lymphoma were observed. Diffuse large B-cell lymphoma (DLBCL) was the most frequent B-cell NHL subtype (55.8% of all B-cell NHLs). The subtype distributions were similar between bionaïve patients and those treated with tumour necrosis factor inhibitors (TNFi). For other bDMARDs, the numbers of cases were too small to draw any conclusions. Patients with RA developed more DLBCLs and less chronic lymphocytic leukaemia compared with the general population.ConclusionThis large collaborative analysis of European registries has successfully collated subtype information on 533 lymphomas. While the subtype distribution differs between RA and the general population, there was no evidence of any modification of the distribution of lymphoma subtypes in patients with RA treated with TNFi compared with bionaïve patients.

Rheumatoid arthritis and lymphoma: Incidence, pathogenesis, biology, and outcome

“…Epstein‐Barr virus (EBV) positivity, a possible surrogate marker for immunosuppression, was evident in only 17% of cases . This finding was recently verified by a European registry study that included 124 997 patients with RA . Here, similar results were observed in lymphoma subtype, with no difference noted between patients treated with anti TNF and those who received biological disease modifying antirheumatic drugs (DMARDS) or bio‐naïve patients.…”

“…Here, similar results were observed in lymphoma subtype, with no difference noted between patients treated with anti TNF and those who received biological disease modifying antirheumatic drugs (DMARDS) or bio‐naïve patients. Regardless of the type of treatment given for RA (anti‐TNF, MTX, or others), the most common lymphoma subtype was DLBCL, occurring in 249/533) 47%) of all lymphomas diagnosed …”

Immune rebalancing by oral immunotherapy: A novel method for getting the immune system back on track

“…45,46 Data also suggest that anti-TNF agents increase the risk of non-Hodgkin's lymphoma in patients with IBD. [47][48][49][50] However, other studies have suggested that the overall risk of lymphoma does not differ significantly from untreated patients and instead correlates with the degree of disease activity rather than therapy type. 51 Recent analyses of patients with RA found that the pooled odds ratio for developing a malignancy was 3.3 and the number needed for harm was 154 per additional malignancy, within a treatment period of 6-12 months.…”

“…Similarly, there is evidence that there is a dose‐dependent risk of malignancy in patients with RA who were treated with anti‐TNF therapy . Data also suggest that anti‐TNF agents increase the risk of non‐Hodgkin's lymphoma in patients with IBD . However, other studies have suggested that the overall risk of lymphoma does not differ significantly from untreated patients and instead correlates with the degree of disease activity rather than therapy type .…”

Cutaneous lymphomas appearing during treatment with biologics: 44 cases from the French Study Group on Cutaneous Lymphomas and French Pharmacovigilance Database

“…Dear Editor , Controversy exists regarding the risk and prognosis of lymphomas during treatment with biologics . Risk evaluation must consider the underlying medical condition – as chronic inflammatory diseases are associated with an excess risk of lymphoma – and ongoing treatments (azathioprine, ciclosporin) .…”