Table 2.
Population cellular kinetic parameter estimates of liso-cel and bootstrap evaluation
| Parametera | Interpretation | Estimateb | Estimateb, %RSE | Estimate, 95% CIc | BSV | BSV, %RSE | BSV, 95% CI |
|---|---|---|---|---|---|---|---|
| Tlag, days | Lag phase duration | 3.27 | 10.8 | (2.71–3.97) | 66.5 | 13.5 | (49.7–79.6) |
| Tgro, days | Growth phase duration | 6.02 | 5.6 | (5.27–6.53) | – | – | – |
| Cmax, copies/μg | Maximum liso-cel transgene levels | 23,600 | 10.4 | (18,900–29,900) | 91.5 | 6.9 | (78.4–105) |
| Tdbl, days | Doubling time during growth phase | 0.755 | 5.3 | (0.667–0.821) | 21.0 | 13.6 | (14.6–26.4) |
| Fβ, fraction | Fraction of Cmax that appears in the terminal (β) phase | 0.00659 | 12.1 | (0.00529–0.00820) | – | – | – |
| HLα, days | Initial (α-phase) decline half-life | 5.00 | 9.1 | (4.15–5.90) | 97.7 | 7.2 | (83.9–114) |
| HLβ, days | Terminal (β-phase) half-life | 352 | 23.0 | (241–647) | – | – | – |
| RUV, % | Residual unexplained variability | 91.5 | 3.0 | (86.2–97.9) | – | – | – |
| Parametera | Interpretation | Estimateb | Estimateb, %RSE | Estimate, 95% CIc | As fold-change over covariate range |
|---|---|---|---|---|---|
| Cmax~Age | Change in Cmax, relative to age of 63 years | – 0.0330 | 14.4 | (– 0.0401 to – 0.0201) |
2.49, Age 18 years 0.24, Age 86 years |
| Cmax~Toci|CS | Change in Cmax with Toci and/or CS use for CRS and/or NE treatment | 0.670 | 43.1 | (0.172–1.42) | 1.67, Toci|CS |
| HLα~SPD | Change in HLα, relative to SPD per IRC before LDC of 22.5 cm2 | 0.187 | 19.0 | (0.108–0.256) |
0.37, SPD 0.8 cm2 1.55, SPD 419 cm2 |
| HLα~Toci|CS | Change in HLα with Toci and/or CS use for CRS and/or NE treatment | 1.31 | 26.5 | (0.744–2.25) | 2.31, Toci|CS |
| Tdbl~Age | Change in Tdbl, relative to age of 63 years | 0.00660 | 27.3 | (0.00308–0.00968) |
0.70, Age 18 years 1.15, Age 86 years |
| Tlag~LDH | Change in Tlag, relative to LDH before LDC of 269 U/L | 0.294 | 29.8 | (0.137–0.499) |
0.74, LDH 112 U/L 2.11, LDH 11,900 U/L |
| Tlag~Toci|CS | Change in Tlag with Toci and/or CS use for CRS and/or NE treatment | – 0.384 | 18.5 | (− 0.502 to − 0.199) | 0.62, Toci|CS |
BSV between-subject variability, CI confidence interval, Cmax maximum transgene levels, CRS cytokine release syndrome, CS corticosteroids, Fβ fraction of Cmax that appears in the β or terminal phase, HLα initial (α phase) decline half-life, HLβ terminal (β phase) half-life, IRC Independent Review Committee, LDH lactate dehydrogenase, NE neurological event, RSE relative standard error, RUV residual unexplained variability, SPD sum of the product of perpendicular diameters, Tdbl doubling time during growth phase, Tgro growth phase duration, Tlag lag phase duration, Toci tocilizumab
aParameter values were centered on the following values, reflecting the central tendency of the patient characteristics (age of 63 years, SPD of 22.5 cm2, and LDH of 269 U/L) and no tocilizumab and/or corticosteroid use
bEstimate and estimate %RSE were given from the importance sampling step
cEstimate 95% CI was given from analysis of 500 replicate bootstrap fits, 4 of which failed with termination errors and were not included in these summaries