Immunophenotypic analysis in participants with Kaposi sarcoma following pomalidomide administration

Abstract

Objective: The aim of this study was to evaluate baseline differences by HIV status and the impact of pomalidomide on lymphocyte counts and T-cell subsets in patients with Kaposi sarcoma. Design: We prospectively evaluated CD4+ and CD8+ T-cell phenotypes in 19 participants with Kaposi sarcoma enrolled on a phase 1/2 study of pomalidomide (NCT01495598), seven without HIV and 12 with HIV on antiretroviral therapy. Methods: Trial participants received pomalidomide 5 mg orally for 21 days of 28-day cycles for up to 1 year. Flow cytometry was performed on peripheral blood mononuclear cells at baseline, after three cycles, and at end-of-treatment. Lymphocyte count and T-cell subset comparisons were evaluated by Wilcoxon signed-rank and Mann--Whitney tests. Results: At baseline, HIV+ participants had lower CD4+ cell counts (median 416 vs. 742 CD4+ T cells/μl, P = 0.006), and a decreased proportion of CD57+ (senescent) CD8+ T cells (P = 0.007) compared with HIV- participants. After three cycles, pomalidomide led to an increased proportion of CD45RO+CD27+ (central memory) CD4+ (P = 0.002) and CD8+ (P = 0.002) T cells, a decrease in CD45RO-CD27- (effector) CD4+ cells (P = 0.0002), and expansion of CD38+/HLADR+ (activated) CD4+ (P = 0.002) and CD8+ (P ≤ 0.0001) T cells. Increased numbers of activated CD8+ T cells persisted at end-of-treatment (P = 0.002). After three cycles and at end-of-treatment, there was reduction in the proportion of CD57+ (senescent) CD4+ (P = 0.001, 0.0006), and CD8+ (P =  < 0.0001, 0.0004) T cells. Conclusion: Administration of pomalidomide decreased T-cell senescence and increased T-cell activation in patients with Kaposi sarcoma, suggesting pomalidomide activity in Kaposi sarcoma stems in part from its immunomodulatory effects.