Article Figures & Data
Figures
- FIGURE 1.
(A and B) Increase in rituximab binding on days 3 and 6 after treatment with escalating doses of 177Lu-lilotomab in Raji cells (A) and Raji2R cells (B). (C) Rituximab binding in Raji2R cells relative to untreated Raji cells when considering average of horizontal plateau from B. *P < 0.05. **P < 0.005. n = 3.
- FIGURE 2.
(A and B) Luminescence (RLU) representative of effector-cell binding to rituximab in Raji cells (A) and Raji2R cells (B) treated with 1 μg/mL 177Lu-lilotomab or PBS (untreated). (C) Relative change in effector-cell binding to rituximab in untreated and in 1 μg/mL 177Lu-lilotomab–treated Raji2R cells relative to untreated Raji cells. **P < 0.05. n = 3–4.
- FIGURE 3.
Average tumor volume ± SE in Raji2R-xenografted mice treated with PBS, rituximab, and 150 and 350 MBq/kg concentrations of 177Lu-lilotomab as monotherapy or in combination with rituximab. n = 10. (A) Curve built using extrapolation of tumor volumes after euthanasia. ♦ = timepoints of observed significant synergistic effects (P < 0.05). (B) Curve built keeping constant tumor volume after euthanasia. * = timepoints observed to be significantly different from 177Lu-lilotomab monotherapy (P < 0.05).
- FIGURE 4.
Kaplan–Meier survival curves of Raji2R-xenografted mice treated with PBS, rituximab, and 150 and 350 MBq/kg concentrations of 177Lu-lilotomab as monotherapy or in combination with rituximab. n = 10. Endpoint is tumor diameter larger than 20 mm. Gray dots = censored animals.
- FIGURE 5.
Survival of Raji2R-xenografted mice treated with PBS, rituximab, and 150 and 350 MBq/kg concentrations of 177Lu-lilotomab as monotherapy or in combination with rituximab. Diamonds represent mice euthanized because study ended (at 114 d) or because there were symptoms of sickness or discomfort.
Tables
- TABLE 1
Fold Change in Average Tumor Volume from Baseline of Combination Therapies vs. Corresponding Monotherapies and Bliss Synergy Interaction Values
177Lu-lilotomab (MBq/kg) Fold change from day 0 Study day Without rituximab With rituximab Interaction value 3 0 2.2 2.2 150 1.7 1.6 0.99 (0.41, 2.37) 350 2.3 1.7 0.77 (0.32, 1.84) 7 0 6.1 5.5 150 3.3 2.4 0.80 (0.33, 1.91) 350 2.7 1.6 0.66 (0.28, 1.57) 9 0 9.2 8.9 150 4.4 3.0 0.70 (0.29, 1.68) 350 3.1 1.6† 0.53 (0.22, 1.23) 10 0 11.8 10.6 150 4.3 3.1 0.79 (0.33, 1.89) 350 3.2 1.7 0.61 (0.26, 1.46) 13 0 20.4 16.6 150 5.0 3.2 0.79 (0.33, 1.89) 350 3.1 1.3† 0.51 (0.22, 1.23) 15 0 36.2 28.8 150 5.7 3.3 0.74 (0.31, 1.77) 350 3.3 1.3† 0.50 (0.21, 1.21) 17 0 57.8 42.6 150 7.7 3.5* 0.61 (0.25, 1.47) 350 3.5 1.0† 0.39 (0.16, 0.94)‡ 20 0 116.6 80.2 150 10.2 4.2* 0.60 (0.25, 1.43) 350 4.1 1.0† 0.36 (0.15, 0.86)‡ - TABLE 2
Median Survival Time of Mice Treated with NaCl, Rituximab, 150 and 350 MBq/kg Concentrations of 177Lu-Lilotomab and Combination Therapies with 20-mm Tumor Diameter as Endpoint
Treatment group Median survival ± SE (d) 4×NaCl 13 ± 0 4 × 10 mg/kg rituximab 13 ± 3 150 MBq/kg 177Lu-lilotomab 24 ± 4*† 350 MBq/kg 177Lu-lilotomab 38 ± 11*† 150 MBq/kg 177Lu-lilotomab + rituximab 31 ± 5*† 350 MBq/kg 177Lu-lilotomab + rituximab 70 ± 8*† - TABLE 3
Bliss Synergy Interaction Values Calculated Using Hazards Found Through Cox Proportional-Hazards Model Fitting to Mice Survival
Treatment group Interaction value P 150 MBq/kg 177Lu-lilotomab + rituximab 0.88 (0.30–2.63) 0.85 350 MBq/kg 177Lu-lilotomab + rituximab 0.83 (0.22–3.15) 0.82 Endpoint is tumor diameter larger than 20 mm. Data in parentheses are 90% confidence intervals.
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