Presence of autoimmune disease affects not only risk but also survival in patients with B‐cell non‐Hodgkin lymphoma
Date
2018-01-10
Authors
Kleinstern, Geffen
Averbuch, Mor
Abu Seir, Rania
Perlman, Riki
Ben Yehuda, Dina
Paltiel, Ora
Journal Title
Journal ISSN
Volume Title
Publisher
John Wiley & Sons, Ltd.
Abstract
Although autoimmune diseases (AIDs) are known to predispose to non‐Hodgkin lymphoma
(NHL), their association with NHL prognosis has rarely been investigated. We examined
associations between autoimmunity and B‐cell NHL onset by comparing AID history
(determined by self‐report and medication review and supplemented by chart review where
possible) among 435 adult B‐NHL patients in Hadassah‐Hebrew University Medical Center,
diagnosed 2009‐2014, and 414 age‐and‐sex frequency‐matched controls. We examined AIDs
as a whole, B‐ and T‐cell–mediated AIDs, and autoimmune thyroid diseases. Among cases,
we used Kaplan‐Meier and Cox regression models to assess the association of AID with overall
survival and relapse‐free survival, adjusting for prognostically important patient and disease
characteristics such as Ki67% staining, International Prognostic Index, rituximab treatment, and
histological subgroup.
Autoimmune diseases were associated with B‐NHL (odds ratio [OR] = 1.95; 95% confidence
interval (CI), 1.31‐2.92), especially AIDs mediated by B‐cell activation (OR = 5.20; CI, 1.90‐14.3),
which were particularly associated with marginal zone lymphoma (OR = 19.3; CI, 4.59‐80.9). We
found that time to relapse for all B‐NHL patients with AIDs was significantly shorter (mean
of 49.21 mo [±3.22]) than among patients without AID (mean of 59.74 mo [±1.62]), adjusted
hazard ratio [HRadj] = 1.69 (CI, 1.03‐2.79). Specifically, in patients with diffuse large B‐cell
lymphoma, of whom 91.8% had received rituximab, a history of B‐cell–mediated AIDs was
associated with shorter relapse‐free survival and overall survival, HRadj = 8.34 (CI, 3.01‐
23.1) and HRadj = 3.83 (CI, 1.20‐12.3), respectively.
Beyond confirming the well‐known association between AIDs and B‐NHL, we found that AID is
an adverse prognostic factor in B‐cell lymphoma, associated with a shortened time to relapse,
suggesting that there are specific therapeutic challenges in the subgroup of patients suffering
from both these diseases. Further work is required to address mechanisms of resistance to
standard treatment in the setting of AID‐associated B‐NHL. In the era of immunotherapy, these
findings have particular relevance.
Description
Keywords
autoimmune disease , diffuse large B‐cell lymphoma , non‐Hodgkin lymphoma , risk , survival