Immune reconstitution and evolution of B-cell–stimulating cytokines after R-CHOP therapy for HIV-associated DLBCL

Abstract

HIV infection is associated with an increased risk of diffuse large B cell lymphoma (DLBCL) that persists despite the advent of combined anti-retroviral therapy. In this prospective study, we analyzed the evolution of B cell activating cytokines (IL-6, IL-10 and BAFF) and the co-evolution of main functional subsets of circulating B and T cells in 51 patients with HIV-associated DLBCL treated with R-CHOP. R-CHOP therapy was associated with a decrease of IL-10, whilst IL-6 levels fluctuated and BAFF levels increased during the first 3 months and decreased thereafter. We observed a rapid rise in CD19+ B cells composed mostly of naïve B cells whereas marginal zone-like B cells and memory B cells recovered gradually. With a median follow-up of 41 months, PFS and OS at 5 years were 61.8% (95CI 47.6-80.4%) and 67.4% (95CI 53.4-85.0%), respectively. Progression (17.5%) and sepsis (12.5%) were the main causes of death. Baseline risk factors for death and progression were poor R-IPI (p=0.049), NK cell lymphopenia (p=0.001), lower proportion of naïve B cells among B cell compartment (p=0.017) and higher IL-6 serum levels (p=0.001). Our data suggest that patients treated with R-CHOP for HIV-associated DLBCL have a disturbed peripheral B cell compartment and that the low pool size of circulating naïve B cells affects negatively clinical outcome in these patients. In an era of rapid development of B cell-depleting therapies including B cell-targeting CAR-T cells, baseline and post-treatment assessment of perturbations within non-tumoral B cells counterpart are warranted for proper risk profiling in HIV-associated DLBCL.