Figure 7. The dose and regimen of bispecific T cell engager (BiTE) strongly influenced tumor control and CD19 evolution.

(a) Three doses (high, medium, and low) and regimens (scheme 1 and 2) were evaluated in the simulations. Starting doses were applied in the first week of cycle 1 only. The high dose with scheme 1 is the clinically approved dose and regimen of blinatumomab for the treatment of B cell acute lymphoblastic leukemia; (b) Simulated blood B cell profiles under different T:B ratios and B cell growth rates in 22-week treatment; (c–e) Different dose levels, and schemes were explored in respective conditions. Simulated blood B cell profiles and CD19 evolution were shown. Gray line and shaded regions represent baseline CD19 expression; (f) The favorable dosing regimen under each condition. The favorable dosing regimen was determined by comparing B cell killing efficacy, CD19 evolution, and total dose, in this order of priority, respectively. B (200 /μL), baseline B cell density in blood is assumed to be 200 /μL; High (b–e) and low CD19 expressions were the mean level of CD19 expression per B cell and set as 3 × 10⁴ and 1 × 10⁴, respectively; High growth and low growth of B cells were set to 0.071 /day and 0.0071 /day; T cell density change is not included in this proof-of-concept simulations.