Juliette Rocca1, Maxime Beydon2, Veronique Le Guern3, Eric Hachulla4, Jean Jacques Dubost5, sandrine jousse joulin6, Valerie Devauchelle7, Jacques-Eric Gottenberg8, Olivier Vittecoq9, Christian Lavigne10, Jean Schmidt11, Christian Marcelli12, Claire Larroche13, Xavier Mariette14, Raphaèle Seror15 and Gaetane Nocturne16, 1APHP, Paris, France, 2Université Paris Cité, Paris, France, 3Hôpital Cochin, Paris, France, 4University of Lille, LILLE, France, 5University Hospital of Clermont Ferrand, Rheumatology, Clermont-Ferrand, France, 6Roche, Brest, France, 7Université de Bretagne Occidentale, Brest, France, 8University of Strasbourg, Strasbourg, France, 9CHU de Rouen, ROUEN, France, 10CHU Angers, Angers, France, 11CHU Amiens, Amiens, France, 12CHU Caen, Caen, France, 13APHP, Bobigny, France, 14Paris-Saclay University, Rueil Malmaison, Ile-de-France, France, 15University Hospital Paris-Saclay, Le Kremlin Bicêtre, France, 16APHP, Le Kremlin Bicêtre, France
Background/Purpose: Primary Sjögren Syndrome (pSS) patients present an increased risk of Non-Hodgkin lymphoma (NHL). There is no consensus on the therapeutic management of low-grade NHL. Two strategies can be proposed; either a ''wait and see'' strategy or active therapeutic strategy. The objective of our study was to describe characteristics of NHL in pSS, and identify predictive and prognosis factors of relapse or death.
Methods: This multicentric retrospective cohort study, included all lymphoma patients of the ASSESS cohort, enriched with patients recruited in Internal Medicine and Rheumatology departments in 13 French hospitals. For each patient, we have collected biological and clinical manifestations of pSS, NHL type, staging, prognosis index (MALT-IPI) and treatment strategy. During follow-up, response to treatment and overall survival (OS) were analyzed.
Results: A total of 105 pSS patients who presented a B cell-NHL between 1985 and 2019 were included. Among them, 18 (17%) did not have low-grade B cell lymphoma, including 14 (13%) large B cell lymphoma (DLBCL). Among the 87 pSS patients with a low-grade B cell NHL, the most frequent histologic subtype was mucosa-associated lymphoid tissue (MALT) lymphomas (n=67, 77%). Location was extra-nodal in 46% of the cases including isolated salivary glands involvement in 28% of the cases. 37% of patients had a MALT-IPI score of 2 (high risk) and 86% had an Ann arbor staging of 4. Median follow-up was 8 years [IQR 4.2-14] and OS was 86%.
Overall, 68/87 (78%) patients received a specific treatment for lymphoma; 11 (16%) of them further received rituximab maintenance therapy. Compared with treated patients, untreated patients tended to be older (mean 63.6 vs 56.1, p = 0.053). There was no difference in clinical and biological characteristics of pSS and MALT IPI score. No significant difference in OS was observed between treated and untreated patients (p=0.4).
In univariate analyses, older age (p< 0.001), pulmonary lymphoma location (p= 0.009), MALT IPI score of 2 (p=0,007) and use of Bendamustine (p=0.012) were associated with an increased risk of death. In multivariate analysis, only age (HR= 1.16, p< 0.001) and pulmonary location (HR= 8.4; p=0.008) were associated with death, suggesting a potential indication bias for the risk associated with bendamustine (Table).
In univariate analyses, risk of relapse in treated patients was lower if first line chemotherapy included anti-CD20 (HR 0.39 [0.16-0.95], p=0.04) and decreased with calendar year of LNH diagnosis (p=0.007). Since these 2 data are very related, we did not perform multivariate analysis. Interestingly no relapse occurred in patients who received maintenance therapy with RTX (0/11 events in maintenance therapy group vs 20/53, p = 0.03).
Conclusion: This study based on a large number of pSS patients with lymphoma shows that age and pulmonary location are the main factors associated with the risk of death. Among treated patients, it appears that maintenance therapy with RTX may be associated with a lower risk of relapse. Disclosures: J. Rocca, None; M. Beydon, None; V. Le Guern, None; E. Hachulla, GlaxoSmithKline, Johnson & Johnson, Roche-Chugai, CSL Behring, Bayer, Boehringer Ingelheim, Sanofi-Genzyme; J. Dubost, None; s. jousse joulin, None; V. Devauchelle, Pfizer, Novartis, AbbVie/Abbott, Novartis, Bristol-Myers Squibb(BMS), Roche-Chugai, Galapados; J. Gottenberg, None; O. Vittecoq, None; C. Lavigne, None; J. Schmidt, None; C. Marcelli, None; C. Larroche, None; X. Mariette, AstraZeneca, Bristol Myers Squibb, Galapagos, GSK, Novartis, Pfizer; R. Seror, GlaxoSmithKlein(GSK), Boehringer-Ingelheim, Janssen, Novartis, Amgen; G. Nocturne, Pfizer, Novartis, Eli Lilly, Amgen.
