D2.350 - CVID: the crossroad between immune dysregulation, autoimmunity and cancer

Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder presenting with recurrent infections, autoimmune manifestations and an increased risk of malignancies. The aim of this study is to evaluate the prevalence of tumors in a cohort of CVID patients and its association with clinical and immunophenotype characteristics, including IDDA score.

We performed a retrospective, observational, single center study including 136 patients with CVID followed by the Rare Immunological Diseases Center in Treviso. Data gathered included demographic characteristics, history of hematologic or solid malignancy, immunophenotype analysis and IDDA score at the last immunological visit.

A total of 29/136 patients (21.3%) were diagnosed with cancer. 14 patients (48.3%) had a diagnosis of hematologic malignancy; among them, NHL was the most prevalent (n=10), while the most common type of solid cancer was gastric adenocarcinoma (n=5). Median age at the first diagnosis of cancer was 55 years [IQR: 40-65]. The diagnosis of cancer followed the diagnosis of CVID in 20/29 patients. The median interval from the diagnosis of CVID to the diagnosis of cancer was 3 years [IQR: 0-11]. No significant difference was observed according to sex, systemic or organ specific autoimmune manifestations and enteropathy between patients with and without a history of malignancy. No correlation was observed between IDDA score and incidence of solid malignancies, while hematologic malignancies were slightly associated with higher IDDA scores [p=0.03]. When analysing the white blood cell immunophenotype in relation to the history of malignancies (presence vs absence), we found a statistically significant difference in the levels of CD4+ [35.5 vs 41.5%, p=0.015], CD8+ [38 vs 32.5%, p=0.006], CD4/CD8 [0.9 vs 1.4, p=0.003], CD3+CD57+ [22 vs 15%, p=0.038], CD19+ [8.5 vs 11%, p=0.028]. The EUROclass analysis showed a significant difference in B naïve [86.9 vs 75.2%, p=0.018] and marginal zone B [3.9 vs 13.2%, p=0.01]. 

In conclusion, the data observed in our cohort reflect those reported by literature, confirming a considerable prevalence of cancer in CVID patients, especially non-Hodgkin lymphoma and gastric cancer; the risk increases with age. The statistically significant differences in immunophenotype suggest that a profound immune defect may be essential to malignancies development. Finally, the correlation between IDDA score and hematological malignancies suggests a role of immune dysregulation in the development of clonal lymphoproliferative disease.