Risk of cancer in adults with primary immune thrombocytopenia: a binational population-based real-world cohort study from Denmark and France

Immune dysregulation and immunosuppression occur due to the pathophysiology and management of primary immune thrombocytopenia (ITP), which together may increase the risk of subsequent cancer. We investigated the cancer risk in ITP compared with the general population in a binational cohort study in Denmark and France. We identified 12,456 patients with ITP and 218,971 age- and sex-matched general population comparators from 1980-2018 in Danish and French health registries. All individuals were followed for solid and hematologic cancer. We estimated nation-specific five-year cumulative incidences, cause-specific [csHR], and combined meta-analysis csHR for cancer. We stratified analyses on age and sex. The five-year cumulative incidences of solid cancer in Denmark were 6.7% (95% confidence interval [CI]: 5.9-7.5) in ITP versus 6.1% (95% CI: 6.0-6.2) in comparators driven by differences in female, thorax and upper gastrointestinal cancers, and 8.4% (95% CI: 7.6-9.2) versus 6.0% (95% CI: 5.6-6.4) in France driven by skin and colorectal cancers. The corresponding numbers for hematologic cancer were 2.6% (95% CI: 2.2-3.2) versus 0.4% (95% CI: 0.4-0.5) in Denmark, and 7.6% (95% CI: 6.9-8.3) versus 1.1% (95% CI: 0.9-1.2) in France. Across both countries, differences were driven by leukemia, lymphoma, and other hematologic cancers. The five-year adjusted csHR for solid cancer were 1.3 (95% CI: 1.1-1.5) in Denmark, 1.3 (95% CI: 1.2-1.5) in France, and 1.3 (95% CI: 1.2-1.4) combined. CsHR for hematologic cancer were 7.4 (95% CI: 6.1-9.1) in Denmark, 9.0 (95% CI: 7.5-10.8) in France, and 8.2 (95% CI: 6.8-9.9) combined. Risks were highest during the first year after ITP diagnosis, and in younger and female patients. The risk of cancer following ITP increased, with risk of hematologic cancer in particular. This knowledge should influence treatment and follow-up.