2588: Updated Analyses of Cancer Incidence and Risk Factors in a Large International SLE Cohort

Sasha Bernatsky¹, Rosalind Ramsey-Goldman², Murray Urowitz³, John G. Hanly⁴, Caroline Gordon⁵, Michelle Petri⁶, Ellen Ginzler⁷, Daniel Wallace⁸, Sang-Cheol Bae⁹, Juanita Romero-Diaz¹⁰, Mary Anne Dooley¹¹, Christine Peschken¹², David Isenberg¹³, Anisur Rahman¹⁴, Susan Manzi¹⁵, Soren Jacobsen¹⁶, S. Sam Lim¹⁷, Ronald van Vollenhoven¹⁸, Ola Nived¹⁹, Diane L. Kamen²⁰, Cynthia Aranow²¹, Jill Buyon²², Guillermo Ruiz-Irastorza²³, Francisco Sanchez-Guerrero²⁴, Dafna Gladman²⁵, Paul R. Fortin²⁶, Jennifer LF Lee²⁷, Luck Lukusa²⁷, Graciela S Alarcón²⁸, Joan Merrill²⁹, Kenneth Kalunian³⁰, Manuel Ramos-Casals³¹, Kristjan Steinsson³², Asad Zoma³³, Anca Askanase³⁴, Munther Khamashta³⁵, Ian Bruce³⁶, Murat Inanç³⁷ and Ann Clarke³⁸, ¹Research Institute of the McGill University Health Centre, Montreal, QC, Canada, ²Northwestern University, Chicago, IL, ³Schroeder Arthritis Institute, Krembil Research Institute; University of Toronto Lupus Clinic; Division of Rheumatology, Toronto, ON, Canada, ⁴Dalhousie University, Halifax, NS, Canada, ⁵Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom, ⁶Department of Medicine, Division of Rheumatology, Johns Hopkins University School of Medicine, Timonium, MD, ⁷SUNY Downstate Health Sciences University, Brooklyn, NY, ⁸Cedars-Sinai Medical Center, Los Angeles, CA, ⁹Hanyang University Hospital for Rheumatic Diseases and Hanyang University Institute for Rheumatology Research, Department of Rheumatology, Seoul, South Korea, ¹⁰Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico, ¹¹Raleigh Neurology Associates, Chapel Hill, NC, ¹²University of Manitoba, Winnipeg, MB, Canada, ¹³University College London, London, United Kingdom, ¹⁴Centre for Rheumatology, Division of Medicine, University College London, London, United Kingdom, ¹⁵Lupus Center of Excellence, Autoimmunity Institute, Allegheny Health Network, Pittsburgh, PA, ¹⁶Rigshospitalet, Copenhagen, Denmark, ¹⁷Emory University, Atlanta, GA, ¹⁸Amsterdam University Medical Centers, Amsterdam, Netherlands, ¹⁹Department of Rheumatology, Institution of Clinical Sciences, Lund University Hospital, Lund, Sweden, ²⁰Medical University of South Carolina, Charleston, SC, ²¹Feinstein Institutes for Medical Research, Manhasset, NY, ²²NYU Grossman School of Medicine, New York, NY, ²³Hospital Universitario Cruces, Barakaldo, Spain, ²⁴University Health Network/Sinai Health system, Toronto, ON, Canada, ²⁵Schroeder Arthritis Institute, Krembil Research Institute, Toronto Western Hospital, Department of Medicine, University of Toronto, Toronto, ON, Canada, ²⁶Centre ARThrite - CHU de Québec - Université Laval, Quebec City, QC, Canada, ²⁷RI-MUHC, Montreal, QC, Canada, ²⁸Heersink School of Medicine. The University of Alabama at Birmingham, Birmingham, AL, ²⁹Oklahoma Medical Research Foundation, Oklahoma City, OK, ³⁰University of California San Diego, La Jolla, CA, ³¹Hospital Clinic, Barcelona, Barcelona, Spain, ³²Landspitali University Hospital, Reykjavik, Iceland, ³³Lanarkshire Centre for Rheumatology and Hairmyres Hospital, East Kilbride, East Kilbride, United Kingdom, ³⁴Columbia University Medical Center, New York, NY, ³⁵GSK Gulf, Medical Affairs Department, Dubai, United Arab Emirates, ³⁶University of Manchester, Manchester, United Kingdom, ³⁷Istanbul University, Istanbul, Turkey, ³⁸University of Calgary, Division of Rheumatology, Cumming School of Medicine, Calgary, AB, Canada

Background/Purpose: Many studies of cancer risk in SLE are limited by small sample size or use of administrative data, which rely on billing code diagnoses instead of clinical data. We produced updated estimates cancer risk in the largest-ever cohort of clinically confirmed incident SLE patients.

Methods: Adults with SLE were enrolled (within 15 months of diagnosis) into the SLICC Inception Cohort, across 32 centres. Individuals were followed with annual assessments, where detailed data was collected on Disease Activity Index-2000 (SLEDAI-2K), lupus drugs in the past year, and documentation of cancer diagnoses (by the examining physician at yearly intervals).

We performed univariate and multivariate Cox regression, with baseline demographics (age at SLE onset, race/ethnicity, sex), and time-dependent variables for medications (antimalarials, biologics and other immunosuppressives, corticosteroids), smoking, and SLEDAI-2K. As well as cancer over-all, we evaluated risk factors for the most common cancer types.

Results: Of 1848 new-onset SLE patients enrolled between 1999-2011, 1675 had at least one follow-up; these were the sample for the current analysis. End date was the first of death, last visit, or end of study interval for this analysis (June 21,2021). Baseline demographics are shown in Table 1.

Over 16493 years of follow-up (median follow up, 10 years) 72 cancers occurred (incidence 4. 4 events per 1,000 patient-years). This included 16 breast cancers, 10 non-melanoma skin, 10 lung, 6 hematological, 6 prostate, 5 melanoma, 3 cervical, 3 renal, 3 head and neck, 3 thyroid, 2 gastric, 2 uterine, and one each rectal, sarcoma, thymoma. Adjusted and unadjusted hazard ratios (HR) are shown in Table 2. Multivariate analyses of all cancer types (analyzed together) suggested a higher risk of cancer among patients of older age, males, and those who smoked more than 15 cigarettes a day.

In the multivariate analyses specifically for breast cancer, age at SLE diagnoses remained a risk factor, and antimalarials were associated with a decreased risk. This effect of antimalarials was not clearly seen for any other cancer type. For non-melanoma skin cancer, both age at SLE diagnosis and cyclophosphamide (albeit with a wide confidence interval) were associated with risk. For hematologic cancers, older age was a risk factor in univariate analyses (hazard ratio, HR 1.06, 95% confidence interval, CI 1.01 , 1.12) as was highest quartile of SLEDAI-2k (HR 10.3, 95% CI 1.31 , 81.7), but due to the low number of hematologic cancers, multivariate estimates were less precise and confidence intervals included the null value for all variables.

Conclusion: Our updated analyses of this large, international inception SLE cohort continues to illustrate how different cancer types in SLE might be associated with specific risk factors. Additional follow-up is still needed to precisely determine the potential effects of disease activity (particularly for hematologic malignancies) and medications on cancer risk in SLE.






S. Bernatsky: None; R. Ramsey-Goldman: Ampel Solutions, 2, Calabetta, 2, Exagen, 2, Immunocor, 6; M. Urowitz: None; J. Hanly: None; C. Gordon: AbbVie, 2, Alumis, 2, Amgen, 2, AstraZeneca, 2, Sanofi, 2, UCB Pharma, 2; M. Petri: Alexion, 1, Amgen, 1, AnaptysBio, 1, Annexon Bio, 1, Argenx, 1, Arhros-Focus Med/Ed, 6, AstraZeneca, 1, 5, Aurinia, 1, 5, 6, Axdev, 1, Biogen, 1, Boxer Capital, 2, Cabaletto Bio, 2, Caribou Biosciences, 2, CVS Health, 1, Eli Lilly, 1, 5, Emergent Biosolutions, 1, Exagen, 5, Exo Therapeutics, 2, Gilead Biosciences, 2, GlaxoSmithKlein(GSK), 1, 5, 6, Horizon Therapeutics, 2, Idorsia Pharmaceuticals, 2, IQVIA, 1, Janssen, 1, 5, Kira Pharmaceuticals, 2, MedShr, 6, Merck/EMD Serono, 1, Momenta Pharmaceuticals, 2, Nexstone Immunology, 2, Nimbus Lakshmi, 2, Proviant, 2, Sanofi, 2, Sinomab Biosciences, 2, Thermofisher, 5, UCB, 2; E. Ginzler: None; D. Wallace: None; S. Bae: None; J. Romero-Diaz: None; M. Dooley: None; C. Peschken: AstraZeneca, 2, 5, GSK, 2, 5, Roche, 1, 2; D. Isenberg: None; A. Rahman: None; S. Manzi: AbbVie, 5, Allegheny Singer Research Institute, 10, AstraZeneca, 2, 5, Exagen Diagnostics, Inc, 2, 9, 10, GSK, 2, 5, Lilly, 2, Lupus Foundation of America, 4, Novartis, 2, UCB Advisory Board, 2, Univiersity of Pittsburgh, 10; S. Jacobsen: None; S. Lim: None; R. van Vollenhoven: AbbVie, 2, 6, AstraZeneca, 2, 5, 6, Biogen, 6, Bristol-Myers Squibb(BMS), 2, 5, 6, Galapagos, 2, 5, 6, GlaxoSmithKline, 6, Janssen, 2, 6, MSD/Merck Sharp and Dohme, 5, Novartis, 5, Pfizer, 2, 5, 6, RemeGen, 2, Roche, 5, Sanofi, 5, UCB, 2, 5, 6; O. Nived: None; D. Kamen: None; C. Aranow: AstraZeneca, 2, Bristol-Myers Squibb(BMS), 2, GlaxoSmithKlein(GSK), 2, 5, kezar Inc, 2; J. Buyon: Bristol-Myers Squibb(BMS), 2, GlaxoSmithKlein(GSK), 2, Related Sciences, 1; G. Ruiz-Irastorza: None; F. Sanchez-Guerrero: None; D. Gladman: AbbVie, 2, 5, Amgen, 2, 5, Bristol Myers Squibb, 2, Celgene, 2, 5, Eli Lilly, 2, 5, Galapagos, 2, Gilead Sciences, 2, Janssen, 2, 5, Novartis, 2, 5, Pfizer Inc, 2, 5, UCB, 2, 5; P. Fortin: AbbVie, 1, AstraZeneca, 1, 6, GlaxoSmithKlein(GSK), 1, 6, Roche-Genentech, 1; J. Lee: None; L. Lukusa: None; G. Alarcón: None; J. Merrill: AbbVie, 2, Alexion, 2, Alumis, 2, Amgen, 2, AstraZeneca, 2, 5, Aurinia, 2, Bristol Myers Squibb, 2, 5, EMD Serono, 2, Genentech, 2, Gilead, 2, GlaxoSmithKline, 2, 5, Lilly, 2, Merck, 2, Pfizer, 2, Provention, 2, Remegen, 2, Sanofi, 2, UCB Pharma, 2, Zenas, 2; K. Kalunian: AbbVie/Abbott, 2, Amgen, 5, AstraZeneca, 2, Aurinia, 2, Bristol-Myers Squibb(BMS), 2, Eli Lilly, 2, EquilliumBio, 2, Genentech, 2, Gilead, 2, Janssen, 2, KezarBio, 1, Merck/MSD, 2, Novartis, 2, Pfizer, 2, Remegene, 2, Roche, 2, UCB, 5; M. Ramos-Casals: None; K. Steinsson: None; A. Zoma: None; A. Askanase: AbbVie, 2, Amgen, 2, AstraZeneca, 2, Aurinia, 2, Bristol-Myers Squibb, 2, Celgene, 2, Eli Lilly, 2, Genentech, 2, GSK, 2, Idorsia, 2, Janssen, 2, Mallinckrodt, 2, Pfizer, 2, UCB Pharma, 2; M. Khamashta: GSK, 3, 11; I. Bruce: AstraZeneca, 1, 2, 5, 6, Aurinia, 2, GSK, 1, 2, 5, 6, Janssen, 5, 6, Lilly, 1, UCB, 6; M. Inanç: Boehringer-Ingelheim, 6, Pfizer, 6, UCB, 6; A. Clarke: AstraZeneca, 2, Bristol-Myers Squibb(BMS), 2, GlaxoSmithKlein(GSK), 2, 5, Otsuka, 2, Roche, 2.