The Impact of Autoimmune Disease on Clinical Outcomes of Patients with DLBCL and FL

Introduction

Patients (pts) with autoimmune diseases (AD) are at increased risk of developing non-Hodgkin lymphoma (NHL) (Smedby et al. J Natl Cancer Inst, 2006). The presence of chronic inflammation and use of immunosuppressive medications may contribute to the higher incidence lymphoma in AD pts over the general age-matched population. While previous studies have described outcomes of AD pts with marginal zone lymphoma (MZL), there is no available data on the outcomes of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in this patient population. We investigated characteristics of NHL pts with a concurrent diagnosis of AD with a specific focus on outcomes in DLBCL and FL.

Methods

This was a retrospective cohort study of pts with AD and concomitant NHL diagnosis. NHL pts with AD [including rheumatoid arthritis (RA), systemic lupus erythematous (SLE), Sjogren syndrome (SS) and psoriatic arthritis (PsA)] were identified by searching our institutional database of lymphoma pts. They must have previously received systemic treatment for their AD to be included in the study. We collected data on the AD and treatment, NHL subtype and therapy, stage, and prognostic index. Lymphoma response to therapy was based on the consensus criteria from the International Harmonization Project (Cheson et al. J Clin Oncol, 2007). Descriptive and survival analysis were performed using Fisher’s exact test and Kaplan-Meier methodology for a cohort of patients with DLBCL and FL.

Results

We identified 58 NHL pts who had previously received systemic treatment for an AD. The majority (71%) of affected pts were female and the median age at diagnosis was 60 years (range 22-85 years). The most common NHL subtypes represented were MZL (29%, N=17), DLBCL (26%, N=15), and FL (21%, N=12). RA was the most commonly identified AD (47%, N=27), followed by SLE (31%, N=18), PsA (12%, N=7) and SS (10%, N=6). Therapies received for AD prior to developing lymphoma were heterogeneous: oral methotrexate (40%, N=23), hydroxychloroquine (34%, N=20), anti-TNF agents (14%, N=8), and rituximab (7%, N=4). Twenty-three pts (40%) received multiple therapies for their AD. There was no relationship between the use of anti-TNF agents and the type of lymphoma diagnosed (p=0.81).

In the DLBCL cohort (N=15), stage at diagnosis was I in 13% (N=2), II in 27% (N=4), III in 13% (N=2) and IV in 47% (N=7) pts. IPI was 0-1 in 47% (N=7), 2-3 in 40% (N=6) and 4-5 in 13% (N=2) at diagnosis. Nine pts were treated with R-CHOP, 3 received CHOP, 2 were treated with DA-R-EPOCH and 1 received R-CEOP. Fourteen pts (93%) had a complete response (CR) to therapy and one had a partial response (PR). Only 2 out of the 15 pts had disease progression and neither pt died due to DLBCL. One pt died of unrelated causes. The median OS for pts with DLBCL was not reached with a range of follow-up of 5 to 309 months. Median PFS was 207 months.

In the FL cohort (N=12), stage at diagnosis was I in 42% (N=5), II in 8% (N=1), III in 8% (N=1) and IV in 42% (N=5). FLIPI score was 0-1 in 42% (N=5), 2 in 17% (N=2) and 3-5 in 42% (N=5). All pts were treated with withdrawal of their immunosuppression used to treat their AD. Two pts received no additional therapy, 5 received rituximab monotherapy, and the remaining 4 received other regimens such as FCR, R-bendamustine and R-CHOP. Eight pts (67%) had a CR to therapy, 3 (25%) had a PR and 1 (8%) had stable disease (SD). Of the 2 who were only treated with withdrawal of immunosuppression, 1 had a CR and 1 had SD. Five pts (42%) had disease progression and all 5 were alive at the conclusion of the study. Only 2 pts (17%) with FL died, both of causes unrelated to their lymphoma. For pts with FL, the median OS was not reached with a range of follow-up of 19 to 223 months and the median PFS was 153 months.

Conclusions

To our knowledge, this is the first work describing outcomes of DLBCL and FL pts with concurrent AD. Pts in this cohort had better outcomes when compared with identical NHL subtypes reported in pts without AD. This may reflect different biology of these lymphomas driven by the autoimmune process and/or immunosuppression. The unique clinical characteristics of lymphomas in AD pts should be studied further in order to guide our appropriate lymphoma-directed therapies in this population.