VEXAS syndrome and cancer: Insights about a possible "Tip of the Iceberg". Ambidirectional data from the international AIDA network registries.
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Gavioli Francesco, Caggiano Valeria, Sbalchiero Jessica, Frassi Micol, Crisafulli Francesca, Cavazzana Ilaria, Hinojosa-Azaola Andrea, Martín-Nares Eduardo, Guaracha-Basañez Guillermo Arturo, Torres-Ruiz Jiram, Wiesik-Szewczyk Ewa, Sfriso Paolo, Rizzo Samuele, Schermi Marta, Bindoli Sara, Hernández-Rodríguez José, Gómez-Caverzaschi Verónica, Araújo Olga, Alemanno Annachiara, Giardini Henrique A Mayrink, González-García Andrés, Placido Francesco, Lopalco Giuseppe, Viapiana Ombretta, Tufan Abdurrahman, Koksoy Busra, Mulayim Fatih, Hissaria Pravin, Beecher Mark, Panayiaris Thomas, De Paulis Amato, Dagna Lorenzo, Tomelleri Alessandro, Campochiaro Corrado, Bugatti Serena, Milanesi Alessandra, Ruiz-Irastorza Guillermo, Soto-Peleteiro Adriana, Piga Matteo, Cauli Alberto, Floris Alberto, Conti Fabrizio, Cardamone Chiara, Zorzenon Ilaria, Triggianese Paola, Gurnari Carmelo, Vitetta Rosetta, Prete Marcella, Racanelli Vito, Silvan Francesca, Talarico Rosaria, Mayo-Juanatey Adrián, Alegre-Sancho Juan José, Renieri Alessandra, Bocchia Monica, Sicuranza Anna, Balistreri Alberto, Sorrentino Vincenzo, Frullanti Elisa, Frediani Bruno, Fabiani Claudia, Cantarini Luca, Vitale Antonio
Аннотация
METHODS: The relative risk (RR) of cancer was compared between VEXAS patients and a control cohort comprising individuals with Still's disease, Behçet's disease, and Schnitzler's syndrome. Logistic regression analysis was performed to identify variables potentially associated with cancer development. Patient's data were drawn from the International AutoInflammatory Disease Alliance (AIDA) Network registries for VEXAS syndrome, Still's disease, Behçet's disease, and Schnitzler's syndrome.
RESULTS: Ninety-six VEXAS patients and 2181 controls were enrolled. To minimize selection bias, only subjects aged >60 years were included, yielding 90 and 174 individuals in the exposed and control groups, respectively. The overall RR for cancer in VEXAS patients was 1.93 (95 % Confidence Interval [C.I.] 1.03-3.60, p = 0.036). Logistic regression analysis identified associations between cancer development and relapsing polychondritis (RR = 2.67, 95 %C.I. 1.22-10.64, p = 0.01), the p.Met41Thr mutation (RR = 3.33, 95 %C.I. 1.29-17.33, p = 0.02), elevated serum erythrocyte sedimentation rate (RR = 1.02, 95 %C.I. 1.01-1.05 p = 0.01), and lactate dehydrogenase (RR = 1.02, 95 %C.I. 1.01-1.07 p = 0.04) levels outside of flares.
CONCLUSIONS: VEXAS patients exhibit a significantly increased risk of both hematologic and non-hematologic malignancies compared with controls, particularly among those with RP, p.Met41Thr mutation, and persistent systemic inflammation.