Biochemical and immunologic changes in patients treated with rituximab, lenalidomide, and idelalisib over time. (A) Kinetics of elevation of ALT (upper limit of normal, 56 IU/L) for the first 6 patients treated with rituximab, idelalisib, and lenalidomide (patient 7 did not develop abnormalities). (B) Change in peripheral blood lymphocyte numbers and (C) T-cell activation markers in patient 6, who died of hepatic failure, at study entry (baseline) and during acute liver failure (day 116). Elevation of CD69 and the costimulatory molecules ICOS, 4-1BB (CD137), and OX40 (CD134) on both CD4⁺ and CD8⁺ T cells suggested marked T-cell activation. Percentages shown are the percent of CD4⁺ or CD8⁺ T cells expressing the appropriate marker. NK, natural killer; Pt, patient; Tregs, regulatory T cells.