Serum levels and pharmacokinetic of rituximab in Bi-weekly R-CHOP in elderly patients with DLBCL treated in the RICOVER-60 trial:

Abstract

7537 Background: The combination of Rituximab (R) and CHOP is considered the standard of treatment for DLBCL in elderly patients (pts) but there is hardly any data on the pharmacokinetic of Rituximab in aggressive lymphoma pts. The RICOVER-60 trial using Rituximab + bi-weekly CHOP-14 resulted in improved TTF in 828 elderly DLBCL pts (Blood 106:9a, 2005). Objective: To study serum levels and pharmacokinetic properties of Rituximab when combined with CHOP-14 in elderly DLBCL pts. Methods: Blood samples of 20 pts were taken before and after Rituximab infusion at each chemotherapy cycle. Additional samples were taken after the end of treatment and at the following time points: after 1 week, 1 month, 2 months, 3 months, 6 months and 9 months, respectively. Peak serum samples were taken within a maximum of 30 min, all samples were centrifuged at 1000 g for 10 min (room temperature) and stored at −20 degrees C. Batch samples were shipped to Xendo Laboratories, Groningen, The Netherlands, and analysed. Results: Samples from 20 pts were evaluable for this analysis with 16/20 pts having completed all 8 cycles of treatment, yet. The median (range) of serum Rituximab levels (μg/ml) before each cycle were: #1 0 (0–0); #2 39 (13–62); #3 74 (47–109); #4 95 (40–136); #5 111 (55–157); #6 114 (12–518); #7 125 (72–207);#8 116 (75–304). After therapy median (range) of serum Rituximab levels were: 163 (67–248) at 1 week; 101 (44–163) at 1 month; 55 (1–123) at 2 months; 34 (1–577) at 3 months; 5 (0–103) at 6 months; 1 (0–128) at 9 months. At 9 months samples from 7 pts were evaluable with detectable serum Rituximab levels in 4/7 pts. Conclusion: In the dose dense regimen R+CHOP-14 Rituximab levels increased after each subsequent cycle for the first 4 cycles. During cycle 5- 8 the serum Rituximab levels reached a plateau and decreased constantly after the end of treatment with detectable levels even after 9 months. Based on this data the German High Grade NHL Study Group (DSHNHL) further investigates a densification of Rituximab in the first cycles in order to improve treatment outcome. A final analysis of all 20 pts and a pharmacokinetic model of Rituximab distribution and elimination phase will be presented at the meeting. [Table: see text]