[3420] Preliminary Pharmacokinetic (PK) Analysis of Eastern Cooperative Oncology Group Protocol E4402: Rituximab Extended Schedule or Re-Treatment Trial (RESORT). Session Type: Poster Session, Board #639-III
Brad S. Kahl, Michael E. Williams, Fangxin Hong, Randy Gascoyne, Sandra J. Horning University of Wisconsin, Madison, WI, USA; University of Virginia, Charlottesville, VA, USA; Dana Farber Cancer Institute, Boston, MA, USA; British Columbia Cancer Agency, Vancouver, BC, Canada; Stanford University, Palo Alto, CA, USA
Background: E4402 is a randomized phase III study comparing two different rituximab dosing strategies for patients (pt) with low tumor burden, indolent histology non-Hodgkin
s lymphoma. Eligible pt receive rituximab weekly x 4 and responders are randomized to receive either re-treatment at progression or a scheduled dose every 3 months (mo). Each strategy is continued until the development of rituximab resistance with a primary endpoint of time to rituximab failure. Administration of a single rituximab dose every 3 mo was based on PK data derived from the Pivotal trial (ref) that suggested 25 mcg/mL may be an important threshold to maintain response, and a PK study (ref Gordon) that suggested this level could be maintained with a single dose administered every 3 mo. Methods: Rituximab levels were measured within 30 minutes of completion of the 4th infusion and at 12 weeks (time of response assessment). Pt randomized to re-treatment have trough levels measured at 6 mo, at 1st relapse, and at the first restaging after re-treatment. Pt randomized to scheduled rituximab have trough levels measured at 6 and 12 mo and upon progression. Presented here is an analysis of serum rituximab levels in 159 and 161 follicular lymphoma pt with available data of week 4 and week 12, respectively. Results: The median level after the 4th infusion is 316 mcg/mL (range 56.4
754.0 mcg/mL). The median level at 12 weeks is 26.9 mcg/mL (range 0.0 87.7). Fifty-three percent of the patients had levels 
25 mcg/mL at 12 weeks. The median week 4 levels are somewhat lower than the Pivotal trial and a comparison of mean levels indicates a statistically significant difference, (312.9 mcg/mL vs. 450 mcg/mL, p-value < 0.0001). However the week 12 levels are similar (table). No correlation between week 4 and week 12 levels was observed in the 132 follicular lymphoma pt with paired data.
| Time | N | Median (mcg/mL) | STD | Min (mcg/mL) | Max (mcg/mL) |
| E4402 week 4 | 159 | 316.0 | 108.6 | 56.4 | 754.0 |
| Pivotal week 4 | 141 | 460.7 | 187.0 | 115.4 | 996.6 |
| E4402 week 12 | 161 | 26.9 | 19.6 | 0.0 | 87.7 |
| Pivotal week 12 | 104 | 20.2 | 20.8 | 0.0 | 96.8 |
Conclusions: Despite the fact that the E4402 pt are untreated and have a low tumor burden, the week 4 serum drug levels are somewhat lower and the week 12 levels are very similar to the Pivotal trial. The week 4 level is not predictive of the week 12 level. These data suggest that serum levels in nearly half of patients receiving a single rituximab dose every 12 weeks will be below a 25 mcg/mL threshold. Future analysis will correlate week 4 and week 12 levels with initial response to rituximab. Later PK time points will be correlated to the time to rituximab resistance.
Abstract #3420 appears in Blood, Volume 110, issue 11, November 16, 2007
Keywords: Lymphoma Therapy|Rituximab|Pharmacokinetic
Disclosure: Consultancy: Genentech. Research Funding: Genentech. Off Label Use: Rituximab as initial therapy for indolent NHL.
Monday, December 10, 2007 5:00 PM
Session Info: Poster Session: Immunotherapy for Lymphoma, including Radio-Immunotherapy (5:00 p.m.-7:00 p.m.)