Annals of Oncology 14:758-765, 2003
© 2003 European Society for Medical Oncology
Original Paper |
Pharmacokinetic study of patients with follicular or mantle cell lymphoma treated with rituximab as ‘in vivo purge’ and consolidative immunotherapy following autologous stem cell transplantation
1 The Advanced Therapeutics Program, Toronto Sunnybrook Regional Cancer Centre, Sunnybrook and Women’s College Health Sciences Centre, Toronto, Ontario, Canada; 2 Genentech, San Francisco, CA, USA
Received 4 October 2002; revised 16 December 2002; accepted 17 January 2003
Background:
Little is known about the pharmacokinetics of rituximab in an autologous stem cell transplant (ASCT) setting.
Patients and methods:
We evaluated serum rituximab levels in 26 patients with follicular or mantle cell lymphoma treated with a combination of ASCT and immunotherapy. Patients received nine infusions of rituximab (375 mg/m2): one dose as an ‘in vivo purge’ prior to stem cell collection, and two 4-week cycles at 8 and 24 weeks following ASCT. Pre- and post-infusion serum rituximab levels were measured during the purging dose, with doses 1 and 4 of both sets of maintenance rituximab cycles, and 12 weeks and 24 weeks following treatment.
Results:
Rituximab levels were detectable after the first infusion, and peaked at a mean concentration of 463.8 µg/ml after the final dose. Levels remained detectable 24 weeks after completion of treatment. There was a trend toward higher rituximab levels in patients with follicular lymphoma. Serum concentrations achieved during the maintenance cycles were similar to levels observed in patients with measurable lymphoma treated during ‘the pivotal trial’. No correlation was observed between serum rituximab levels achieved in the minimal disease state and the risk of later clinical relapse, nor with the ability to achieve a molecular remission following ASCT.
Conclusions:
The finding that patients treated in minimal disease states and at the time of active disease both achieve similar final serum rituximab concentrations after four infusions suggests that the pharmacokinetics are complex, and may not necessarily correlate with disease burden. The precise factors influencing rituximab clearance in patients with lymphoma are unresolved, and this remains an area of active research.
Key words: autologous stem cell transplantation, pharmacokinetics, rituximab
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