PB1789 EXTRA‐NODAL INVOLVEMENT IN DIFFUSE LARGE B‐CELL LYMPHOMA: PROGNOSTIC IMPACT IN RITUXIMAB TREATED PATIENTS
Authors: M. Grech, A. Giotas, S. Borg Savona, A. Gatt, D.‐J. Camilleri
Journal: HemaSphere (2019)

Background: Extra‐nodal (EN) involvement in diffuse large B‐cell lymphoma (DLBCL) is associated with a worse outcome and involvement of two or more EN sites is an independent risk factor in the R‐IPI score. The R‐IPI does not however consider the prognostic significance of individual sites of EN involvement. The enhanced IPI (NCCN‐IPI) includes bone marrow, central nervous system (CNS), liver, gastrointestinal (GI) tract and lung as unfavourable factors. However, controversies remain regarding the prognostic value of distinct EN sites. Aims: The purpose of our study was to investigate the prognostic significance of individual sites of EN involvement in patients with DLBCL treated with rituximab. Methods: Patients diagnosed with DLBCL between January 2007 and December 2018 were retrospectively identified. Exclusion criteria were primary CNS lymphoma and patients with missing staging information. EN involvement was evaluated using histology reports and PET‐CT, MRI and CT data performed at baseline assessment. The prognostic impact of individual EN sites on overall survival (OS) was assessed. Results: Three hundred and thirteen patients were included in the study with a median age of 66 years (range 18–97 years). EN involvement by DLBCL was present in 235 (75.1%) patients: one site in 141 (45.0%), two sites in 54 (17.3%), three sites in 24 (7.7%) and 4 or more sites in 15 (4.8%) patients. The EN sites involved were as follows: CNS in 8 (2.6%) patients; bone marrow in 32 (13.7%); skeletal in 60 (19.6%) for the entire cohort and in 48/169 (28.4%) patients staged with PET‐CT; naso/oro‐pharynx (including salivary glands and tongue) in 34 (11.0%); orbit in 3 (1.0%); breast in 12 (7.5% of females); kidneys in 27 (8.8%); adrenals in 20 (6.5%); GI tract in 57 (18.6%); liver in 32 (10.4%); pancreas in 17 (5.5%); lung in 45 (14.7%); muscle and soft tissue in 16 (5.2%); bladder in 6 (2.0%); thyroid in 5 (1.6%); testes in 10 (6.9% of males); ovary in 6 (3.7% of females); uterus in 9 (5.6% of females); skin in 13 (4.2%). Patients with EN disease were more likely to have a non‐germinal centre phenotype ( P = 0.02), higher ECOG performance scores ( P = 0.01), higher CRP levels ( P = 0.01) and lower albumin levels ( P &lt; 0.001). There was no significant difference in OS between patients with one EN site and patients with only nodal disease (5‐year OS 59% vs 65%, P = 0.37). However, patients with involvement of two or more EN sites had significantly worse outcome (5‐year OS 38.5%, P &lt; 0.001). On univariate analysis involvement of CNS ( P = 0.03), bone marrow ( P = 0.01), kidneys ( P = 0.03), lungs ( P = 0.02) and skin ( P = 0.003) were significantly associated with worse OS. On multivariate analysis involvement of CNS ( P = 0.004), bone marrow ( P = 0.03) and skin ( P = 0.04) remained independently associated with worse OS. The prognostic significance of these EN sites was then assessed as a group: patients with any one of the sites involved had a significantly worse OS compared to patients with none (5‐year OS 68% vs 46%, P &lt; 0.001). On multivariate analysis this remained an independent prognostic variable when adjusting for the R‐IPI risk factors (HR: 1.86; 95% CI 1.07–3.24, P = 0.03). Summary/Conclusion: Patients with DLBCL and more than one EN area involved have a worse prognosis compared to patients with one EN area or isolated nodal disease. Among patients with EN disease, the site involved is also associated with outcome. In our study involvement of CNS, bone marrow and skin were associated with a worse OS, whereas involvement of lung, GI tract and liver were not predictive of poor outcomes.