Panel a shows H R C T scans lungs before after treatment showing improvement; Panel b shows M R I scans spleen showing resolution of nodular lesion after treatment; Panel c shows C T scans thymus demonstrating structural changes before and after therapy; Panel d shows line graphs depicting T-cell subset counts during treatment period; Panel e shows line graphs showing B-cell counts and immunoglobulin changes over time; Panel f shows line graphs indicating changes in transitional B-cells and senescent T-cells; Panel g shows flow cytometry histograms of p S 6 expression in T-cells comparing conditions.
Pulmonary, lymphoproliferation, immunophenotype, and pS6 changes. (A) HRCT scans of the lungs before and after treatment with leniolisib. Treatment resolved consolidation streaks and the “tree-in-bud” pattern (circles). Mosaic attenuation areas persist but are less pronounced compared with pretreatment examination (arrows). (B) MRI scans of the spleen before sirolimus and leniolisib and after treatment with leniolisib. A nodular hypointense area in the splenic parenchyma visible in earlier scans (white arrows) was no longer detectable during treatment with leniolisib. (C) CT scans of the thymus before and after treatment with leniolisib. (D–F) Immunophenotyping during leniolisib treatment. (D) Absolute T cell subset counts. (E) Absolute counts of total and naive B cells and IgM levels. (F) Percentage of transitional B cells, CD21low B cells, and senescent CD8+ T cells. (G) pS6 flow cytometry assay of stimulated and nonstimulated CD4+ and CD8+ T cells from HD (top), and patient pre- (middle), and posttreatment with leniolisib (bottom). Elevated pS6 decreased after treatment with leniolisib. Comp-FITC-A, compensation control fluorescein isothiocyanate; HD, healthy donor; L, left; MFI, mean fluorescence intensity; Pos, posterior; Pt, patient; R, right.