Real-world evidence of mortality and survival rates in 256 individuals with APDS

Abstract

AbstractActivated Phosphoinositide 3-kinase Delta Syndrome (APDS) is a rare genetic disorder that presents clinically as a primary immunodeficiency. Clinical presentation of APDS includes severe, recurrent infections, lymphoproliferation, lymphoma and other cancers, autoimmunity and enteropathy. Autosomal dominant variants in two independent genes have been demonstrated to cause APDS. Pathogenic variants inPIK3CDandPIK3R1, both of which encode components of the PI3-kinase, have been identified in subjects with APDS. APDS1 is caused by gain of function (GOF) variants in thePIK3CDgene while loss of function (LOF) variants inPIK3R1have been reported to cause APDS2. We conducted a review of the medical literature and identified 256 individuals who had a molecular diagnosis for APDS as well as age at last report; 193 individuals with APDS1 and 63 with APDS2. A Kaplan-Meier survival analysis for APDS showed the conditional survival rate at the age of 20 was 87%, age 30 was 74%, age 40 and 50 were 68%. Review of causes of death showed that the most common cause of death was lymphoma, followed by complications from HSCT. The mortality data suggests that the standard of care treatment for APDS, immunoglobulin replacement therapy, appears to prevent most deaths due to severe infection, however, new treatments are needed to mitigate the risk of death from lymphoma and other cancers. This analysis based on real world evidence gathered from the medical literature is the largest study of survival for APDS to date.