AIDS (London, England) · 2023
Immunophenotypic analysis in participants with Kaposi sarcoma following pomalidomide administration.
Клиническое исследование II фазыКлиническое исследование I фазыСтатьяResearch Support, N.I.H., IntramuralПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Lurain Kathryn, Polizzotto Mark N, Krug Laurie T, Shoemaker Griffin, Singh Amrit, Jensen Stig M R, Wyvill Kathleen M, Ramaswami Ramya, Uldrick Thomas S, Yarchoan Robert, Sereti Irini
Аннотация
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.
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.