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MICROENVIRONMENTAL FEATURES REFLECTING IMMUNOCOMPETENCE ARE STRONG OUTCOME DETERMINANTS IN HIV‐ASSOCIATED LYMPHOMA

investigated. We hypothesized that rituximab‐based therapy would improve survival in B‐cell–mediated AID‐associated lymphoma, given its beneficial clinical effect in AID. We aimed to examine the association between pre‐existing AIDs and B‐NHL and the possible influence of AIDs on NHL outcome. Methods: In this hospital‐based case‐control study in Hadassah– Hebrew University Medical Center, we recruited 435 newly‐diagnosed adult (>18 years) CD20+ B‐NHL patients diagnosed 2009 to 2014 and 414 controls frequency‐matched by age and sex to cases. The study is based on questionnaires in Hebrew, English, and Russian that included sociodemographic variables, medical information including a history of AIDs and medications; pathology confirmation; and chart review. We examined the association between NHL and AIDs in general, B‐ and T‐cell–mediated AIDs and autoimmune thyroid diseases, using logistic regression, reporting odds ratios (OR), and 95% confidence intervals (CI). In the second part of the study, we compared overall (OS) and relapse‐free survival (RFS) in B‐NHL patients with and without AID. We constructed Kaplan‐Meier curves for univariate analysis, and multivariable Cox regression models adjusting for important patient and disease characteristics such as Ki67% staining, international prognostic index score (IPI), and histological subgroup. Results: B‐NHL risk was associated with the presence of AIDs (OR = 1.98; 95% CI, 1.01‐3.9) especially those mediated by B‐cell activation (OR = 5.97; 95% CI, 2.3‐15.6). The strongest association was observed for marginal zone lymphoma (OR = 13.2, 95% CI, 4.02‐43.6). Time to relapse for all B‐NHL patients with AIDs was significantly shorter (mean of 49.21 months [±3.22]) than for patients without AID (mean of 59.74 months [±1.62]), hazard ratio (HR) = 1.7 (95% CI, 1.03‐2.79), after adjusting for IPI, Ki67% staining, and histological subgroup. Specifically in DLBCL, in which >99% received rituximab‐based therapy, both RFS and OS were adversely affected by the presence of B‐cell mediated AIDs with HR = 7.84 (95% CI, 2.86‐21.5) and 3.99 (95% CI, 1.24‐12.6), respectively (see figure). Conclusions: Beyond the well‐known association between AIDs and B‐NHL (particularly AIDs mediated by B‐cell activation), we found in addition that AID is an adverse prognostic factor in B‐cell lymphoma. AID‐associated B‐NHL patients have poorer outcomes. Specifically, B‐cell mediated AID results in inferior RFS and OS in DLBCL, suggesting that rituximab‐based therapy does not provide adequate coverage for the subgroup of patients. Further exploration of molecular subtypes and mechanisms of resistance of B‐NHL associated with AID is warranted.