Table 5.
Summary of ofatumumab pharmacokinetic parameter values in patients with Waldenström’s macroglobulinaemia
| Pharmacokinetic parameter | TGA (1,000 mg) | TGB (2,000 mg) | ||
|---|---|---|---|---|
|
| ||||
| n | Geometric mean (%CVb) |
n | Geometric mean (%CVb) |
|
|
| ||||
| CL*, mL/h | 15 | 27·9 (132) | 21 | 13·5 (122) |
| Vss*, L | 15 | 10·0 (21) | 21 | 10·7 (24) |
| t½*, days | 15 | 10·9 (103) | 21 | 23·9 (103) |
|
| ||||
| Course 1† | ||||
|
| ||||
| Cmax Dose 1, μg/mL | 14 | 68·3 (67) | 19 | 72·1 (50) |
| Cmax Dose 3, μg/mL | NE | 19 | 465 (40) | |
| Cmax Dose 4, μg/mL | 13 | 259 (50) | NE | |
| Cmax Dose 5, μg/mL | NA | 18 | 640 (42) | |
| Ctrough prior to Dose 2, μg/mL | 7 | 3·0 (1,725) | 12 | 8·0 (1,084) |
| Ctrough prior to Dose 3, μg/mL | 11 | 13·9 (5,018) | 19 | 121 (184) |
| Ctrough prior to Dose 4, μg/mL | 13 | 23·4 (5,252) | 21 | 181 (252) |
| Ctrough prior to Dose 5, μg/mL | NA | 18 | 249 (230) | |
|
| ||||
| Course 2† | ||||
|
| ||||
| Cmax Dose 1, μg/mL | 9 | 53·2 (68) | 11 | 64·8 (68) |
| Cmax Dose 3, μg/mL | 8 | 554 (34) | 12 | 577 (46) |
| Cmax Dose 5, μg/mL | 10 | 528 (69) | 12 | 803 (44) |
| Ctrough prior to Dose 2, μg/mL | 7 | 8·1 (777) | 10 | 20·4 (828) |
| Ctrough prior to Dose 3, μg/mL | 8 | 144 (122) | 12 | 169 (94) |
| Ctrough prior to Dose 4, μg/mL | 11 | 225 (144) | 12 | 310 (78) |
| Ctrough prior to Dose 5, μg/mL | 11 | 279 (108) | 12 | 384 (58) |
*
Based on post hoc parameter estimates.
†
Course 1 = first course of treatment (Cycle 1); Course 2 = second course of treatment (Redosing Cycle 1 or Cycle 2, depending upon the patient).
%CVb=between-patient coefficient of variation. CL=clearance. Cmax=maximum observed concentration. Ctrough= plasma concentration prior to the start of the next infusion. NA=not available. NE=not evaluated. t½=elimination half-life. TGA=Treatment Group A. TGB=Treatment Group B. Vss=volume of distribution at steady state.