Lymphoma and Other Malignancies in Sjögren’s Disease: Incidence, Predictive Factors, and Mortality Outcomes.

Olga Rusinovich¹, Zulema Plaza², Monica Fernandez Castro³, Jose Rosas Gómez de Salazar⁴, Victor Martinez-Taboada⁵, Alex Olive⁶, Belén Serrano-Benavente⁷, Judit Font-Urgelles⁸, Angel Garcia-Aparicio⁹, Sara Manrique-Arija¹⁰, Jesús Alberto Garcia Vadillo¹¹, Ruth Lopez-Gonzalez¹², Javier Narváez¹³, Maria Beatriz Rodriguez¹⁴, Carlos Galisteo¹⁵, Jorge Juan Gonzalez Martin¹⁶, Paloma Vela Casasempere¹⁷, Rabadán Elena¹⁸, Antonio Naranjo¹⁹, Beatriz Paredes-Romero²⁰, Leyre Riancho-Zarrabeitia²¹, Sheila Melchor Diaz²², Irene Altabás-González²³, Sergi Heredia Martin²⁴, Clara Moriano²⁵, Mª Angeles Blazquez Cañamero²⁶, Paula Estrada-Alarcón²⁷, Enrique Judez²⁸, Nerea Alcorta Lorenzo²⁹, Javier Loricera³⁰, Rosalía Martínez Pérez³¹, Fernando Sánchez-Alonso³² and Jose Luis Andreu³³, ¹Puerta de Hierro University Hospital, Boadilla del Monte, Spain, ²Research Unit, Spanish Society of Rheumatology, Madrid, Spain, Madrid, Spain, ³PUERTA DE HIERRO HOSPITAL, Madrid, Spain, ⁴Hospital Marina Baixa, PALMA DE MALLORCA, Spain, ⁵Facultad de Medicina. Universidad de Cantabria, Santander, Spain, ⁶Solo practice, Barcelona, Spain, ⁷Hospital Gregorio Marañon, Madrid, Spain, ⁸Hospital Universitari Germans Trias i Pujol, Badalona, Spain, ⁹Hospital Universitario de Toledo, Toledo, Spain, ¹⁰Hospital Regional Universitario Málaga, Malaga, Spain, ¹¹Hospital Universitario La Princesa, Madrid, Spain, ¹²Zamora Health Complex, Salamanca, Spain, ¹³Hospital Universitario de Bellvitge, Barcelona, Spain, ¹⁴Canarias University Hospital, La Laguna- Tenerife, Spain, ¹⁵Hospital Parc Taulí, Sabadel, Sabadel, Spain, ¹⁶HM Sanchinarro Univeristary Hospital, Madrid, Spain, ¹⁷Hospital General Universitario Alicante, Alicante, Comunidad Valenciana, Spain, ¹⁸Hospital Universitario Príncipe de Asturias, Alcala de Henares, Spain, ¹⁹Hospital Dr Negrin, PALMAS DE GRAN CANARIA (LAS), Spain, ²⁰Hospital Universitario Infanta Sofía;Universidad Europea de Madrid. Faculty of Medicine, Health and Sports. Department of Medicine; FIIB HUIS-HUHEN, San Sebastian de los Reyes, Spain, ²¹Rheumatology Department. Hospital Sierrallana, Torrelavega, Spain, ²²¹² de Octubre University Hospital, Madrid, Spain, ²³Complejo Hospitalario de Vigo, Vigo, Spain, ²⁴Complex Hospitalari Moisès Broggi, Barcelona, Spain, ²⁵Hospital León, LEON, Castilla y Leon, Spain, ²⁶Hospital Ramon y Cajal, Madrid, Spain, ²⁷Complex Universitari Hospital Moisès Broggi, Barcelona, Spain, ²⁸Albacete University Hospital, Albacete, Spain, ²⁹University Hospital Donostia, san sebastian, Spain, ³⁰Hospital Universitario Marqués de Valdecilla, IDIVAL, Immunopathology Group, Santander , Spain, Santander, Spain, ³¹Hospital Universitario Virgen de Valme, Servicio de Reumatología, Seville, Spain, ³²Sociedad Española de Reumatología, Madrid, Spain, ³³Hospital Universitario Puerta de Hierro, Majadahonda, Spain

Meeting: ACR Convergence 2025

Keywords: Cryoglobulinemia, longitudinal studies, risk factors, Sjögren's syndrome

Session Information

Date: Monday, October 27, 2025

Title: Abstracts: Sjögren’s Disease – Basic & Clinical Science (1680–1685)

Session Type: Abstract Session

Session Time: 1:15PM-1:30PM

Background/Purpose: The association between Sjögren’s disease (SjD) and non-Hodgkin lymphoma (NHL) is well established, although reported standardized incidence ratios (SIRs) vary considerably across studies. In contrast, the risk of solid tumors in SjD remains controversial, with conflicting evidence in the literature. This study aimed to determine the SIRs for lymphoma and other malignancies (both hematologic and solid tumors) in patients with SjD, identify independent predictors of cancer development, and assess the impact of malignancies on overall mortality.

Methods: We conducted a prospective, multicenter observational study including 314 patients with SjD who met the 2002 American-European Consensus Group criteria. Clinical, demographic, and serological data, as well as malignancy incidence and survival outcomes, were prospectively collected over a median follow-up of 9.5 years [IQR 9.2–9.9]. SIRs were calculated using data from the GLOBOCAN project. Independent predictors of lymphoma and other malignancies were identified through multivariate Cox regression analysis. Cancer-related mortality and its impact on overall survival were assessed using relative risk (RR) estimates.

Results: Among the 314 patients, 22 incident malignancies (7.01%) were identified: 11 hematologic (all NHL) and 11 solid tumors. The overall cancer risk was elevated (SIR: 1.68; 95% CI: 1.68–1.69). A markedly increased risk was observed for NHL (SIR: 15.36; 95% CI: 15.32–15.40) and hematologic malignancies overall (SIR: 3.55; 95% CI: 3.54–3.56), while a modest increase was seen for solid tumors (SIR: 1.54; 95% CI: 1.53–1.55). Multivariate analysis identified older age (HR: 1.06; 95% CI: 1.01–1.11), smoking (HR: 3.56; 95% CI: 1.24–10.24), lymphadenopathy (HR: 3.34; 95% CI: 1.33–8.37), splenomegaly (HR: 14.04; 95% CI: 1.36–144.51), and cryoglobulinemia (HR: 9.12; 95% CI: 1.93–43.07) as independent predictors of malignancy. Cryoglobulinemia emerged as the strongest predictor of lymphoma (HR: 11.07; 95% CI: 1.18–103.75). A prior history of cancer significantly differentiated hematologic malignancies from solid tumors (HR: 26.97; 95% CI: 1.26–418.46). Malignancies accounted for 23.8% of all deaths in the cohort (RR: 2.21; 95% CI: 1.18–4.12).

Conclusion: Patients with Sjögren’s disease are at increased risk of developing hematologic malignancies—particularly non-Hodgkin lymphoma—and, to a lesser extent, solid tumors. Cryoglobulinemia emerged as the strongest independent predictor of lymphoma. Malignancies significantly contribute to mortality, highlighting the need for targeted surveillance and timely intervention in high-risk patients. Further research is needed to validate findings and guide personalized approaches to improve outcomes.

Disclosures: O. Rusinovich: None; Z. Plaza: None; M. Fernandez Castro: None; J. Rosas Gómez de Salazar: None; V. Martinez-Taboada: None; A. Olive: None; B. Serrano-Benavente: None; J. Font-Urgelles: None; A. Garcia-Aparicio: AbbVie/Abbott, 6, AstraZeneca, 6, GlaxoSmithKlein(GSK), 1, 2, 6, UCB, 6; S. Manrique-Arija: None; J. Garcia Vadillo: None; R. Lopez-Gonzalez: None; J. Narváez: None; M. Rodriguez: None; C. Galisteo: None; J. Gonzalez Martin: None; P. Vela Casasempere: None; R. Elena: None; A. Naranjo: None; B. Paredes-Romero: None; L. Riancho-Zarrabeitia: None; S. Melchor Diaz: None; I. Altabás-González: None; S. Heredia Martin: None; C. Moriano: None; M. Blazquez Cañamero: Astrazeneca, 12, conference registrations, Gsk, 6, Novartis, 12, conference registrations, Rubio, 12, conference registrations; P. Estrada-Alarcón: None; E. Judez: None; N. Alcorta Lorenzo: None; J. Loricera: AbbVie/Abbott, 5, AstraZeneca, 2, 5, 6, Celgene, 2, 5, 6, Eli Lilly, 5, Janssen, 5, Merck/MSD, 2, 5, 6, Novartis, 2, 5, 6, Pfizer, 5, Roche, 2, 5, 6, UCB, 2, 5, 6; R. Martínez Pérez: None; F. Sánchez-Alonso: None; J. Andreu: None.

To cite this abstract in AMA style:

Rusinovich O, Plaza Z, Fernandez Castro M, Rosas Gómez de Salazar J, Martinez-Taboada V, Olive A, Serrano-Benavente B, Font-Urgelles J, Garcia-Aparicio A, Manrique-Arija S, Garcia Vadillo J, Lopez-Gonzalez R, Narváez J, Rodriguez M, Galisteo C, Gonzalez Martin J, Vela Casasempere P, Elena R, Naranjo A, Paredes-Romero B, Riancho-Zarrabeitia L, Melchor Diaz S, Altabás-González I, Heredia Martin S, Moriano C, Blazquez Cañamero M, Estrada-Alarcón P, Judez E, Alcorta Lorenzo N, Loricera J, Martínez Pérez R, Sánchez-Alonso F, Andreu J. Lymphoma and Other Malignancies in Sjögren’s Disease: Incidence, Predictive Factors, and Mortality Outcomes. [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/lymphoma-and-other-malignancies-in-sjogrens-disease-incidence-predictive-factors-and-mortality-outcomes/. Accessed .

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