791 – Immunologic Responses to Pomalidomide and Liposomal Doxorubicin for Kaposi Sarcoma Treatment

Background

Kaposi sarcoma herpesvirus (KSHV) is the causative agent of Kaposi sarcoma (KS), multicentric Castleman disease (MCD), and KSHV-associated inflammatory cytokine syndrome (KICS). In people with HIV (PWH), KS can occur alone or with MCD or KICS. Liposomal doxorubicin (DOX) and pomalidomide (POM) are FDA-approved therapies for KS alone. A phase I/II study combining POM/DOX identified varying KS response rates (RR) by group. In participants (pts) in Group 1 (G1: KS alone) the RR was 71%, in pts in Group 2 (G2: KS with MCD or KICS), the KS RR was 45%. Evaluating the immunologic response may further our understanding of the RR differences.

Methods

51 pts (49 PWH, G1- 37 pts, G2- 14 pts) were enrolled in the POM/DOX study. Pts received intravenous DOX at 20 mg/m² on day 1 combined with oral POM once daily on days 1 to 21 of a 28-day cycle. After adjusting for quality control aspects, we analyzed T-cell subsets among 23 participants using flow cytometry of peripheral blood mononuclear cells (PBMCs) at baseline and cycle 1 day 28 (C1D28). We evaluated markers of T-cell activation (CD38 and HLA-DR), exhaustion (PD-1), and senescence (CD57). Wilcoxon rank sum and signed rank tests were used to analyze significant differences between groups and paired changes across time points for flow cytometry, respectively.

Results

Among all pts, there was an increase from baseline to C1D28 in the percentage of CD4 T-cells (P=0.0004) and a decrease in the percentage of CD8 T-cells (P=0.0009). The percentage of PD-1⁺ CD4 T-cells and PD-1⁺ CD8 T-cells were higher at baseline in G2 than in G1 (P=0.01, P=0.007, respectively, Figure 1). Among the effector memory (CD45RO⁺CD27^–) T-cell population, G2 had higher percentages of PD-1⁺ CD4 T-cells (P=0.03), CD38⁺HLA-DR⁺ CD4 T-cells (P=0.02), and CD38⁺HLA-DR⁺ CD8 T-cells (P=0.02) than G1 at baseline. Among the naïve (CD45RO^–CD27⁺) T-cell population, G1 had higher levels of CD38⁺HLA-DR^– CD4 T-cells (P=0.007) compared to G2. On assessing baseline to C1D28 changes between the groups, only the percentage of CD38⁺HLADR^– central memory (CM, CD45RO⁺CD27⁺) CD4 T-cells increased and CD38^–HLADR⁺ CM CD4 T-cells decreased in G1 compared to G2 (P=0.05, P=0.02).

Conclusions

Patients with KS and MCD or KICS had increased expression of exhaustion markers on their effector memory CD4 and CD8 T-cell subsets. Thus, phenotypic differences at baseline in T-cells may inform differences observed in treatment response by group.