High Frequency of Identical Clonal Immunoglobulin DNA in Pre-Treatment Tumor and Plasma from Untreated Patients with HIV-Associated Lymphoma: Prospective Multicenter Trial of the AIDS Malignancies Consortium (AMC 064)

摘要

Patients with HIV are at increased risk for developing B-cell lymphomas likely due in part to chronic antigen stimulation leading to clonal immunoglobulin (Ig) gene rearrangements. Clonal Ig DNA has been identified in the plasma in patients with lymphomas. However, next-generation sequencing (NGS)-based identification of circulating Ig clonotypes has not been well-characterized, particularly in HIV-related lymphomas. The AIDS Malignancies Consortium (AMC) enrolled 51 untreated patients with HIV-related B-cell lymphomas and analyzed paired tumor and plasma specimens for Ig clonotypes using an NGS-based approach (AMC064, ). Lymphoma-specific clonotypes (>5% frequency) were identified in 83% (33/40) of the tumor specimens. Results from paired tumor and plasma specimens showed identical circulating clonotypes in the plasma from 97% (32/33) of patients. High International Prognostic Index (IPI) scores of 3–4 among patients with diffuse large B-cell lymphoma correlated with higher lymphoma molecules/million diploid genomes in the plasma compared with lower IPI scores of 0–2, median 77335 vs. 6876, p = 0.005. Further prospective studies are merited to determine whether plasma clonal Ig DNA has prognostic significance as a biomarker in HIV-related lymphomas and if the presence of lower frequency detection (≤ 5%) may have similar implications.