Multidisciplinary Delphi consensus on malignancy screening in patients with common variable immunodeficiency

Common variable immunodeficiency (CVID) is the most frequent symptomatic inborn error of immunity (IEI) in adults and is characterized by recurrent infections, immune dysregulation, and an increased risk of malignancy. Cancer represents a major cause of morbidity and mortality in this population, particularly hematological malignancies and gastric carcinoma. Data from the Spanish cohort report malignancy rates of up to 15%, with substantial variability in surveillance practices across centers. Despite this well-established cancer predisposition, standardized, evidence-based screening strategies are lacking, and no specific recommendations for malignancy surveillance in CVID currently exist. Therefore, this two-round Delphi consensus aimed to develop expert-based recommendations for cancer screening and surveillance in patients with CVID.

The process included 39 multidisciplinary experts from 22 Spanish hospitals, including adult and pediatric centers, who evaluated a structured questionnaire comprising 87 statements across four domains: epidemiology/risk factors, solid tumors, hematological malignancies, and immunological biomarkers. The questionnaire was developed from a targeted literature review, and statements were rated using a five-point Likert scale, with consensus defined as ≥70% agreement/disagreement.

Overall, 70 statements, corresponding to 80.5%, reached agreement. Consensus supported systematic genetic testing at diagnosis and annual immunophenotyping to identify malignancy risk markers. In adults, baseline upper gastrointestinal endoscopy with histology-guided follow-up was recommended, together with annual Helicobacter pylori testing and monitoring of micronutrients and pernicious anemia-related antibodies. Hematological surveillance should include systematic evaluation of lymphadenopathy, with imaging ± biopsy when indicated, and bone marrow aspirate/biopsy in persistent (>6 months) cytopenias, while unexplained weight loss should prompt computed tomography imaging. Pediatric management should remain individualized and age-adapted, avoiding direct extrapolation from adult screening strategies.

This Delphi consensus proposes a structured approach to malignancy screening and surveillance in CVID from the time of diagnosis, encompassing gastric, hematological, and immunological assessment. These cancer-focused recommendations are intended to complement existing CVID management guidance, supporting earlier detection of malignancy and reducing variability in clinical practice.