uximab was detectable in the serum of patients 3to 6 months after completion of treatment.
Based on a population pharmacokinetic analysis of data from 298 NHL patients who receivedrituximab once weekly or once every three weeks, the estimated median terminal eliminationhalf-life was 22 days (range, 6.1 to 52 days). Patients with higher CD19-positive cell counts orlarger measurable tumor lesions at pretreatment had a higher clearance. However, doseadjustment for pretreatment CD19 count or size of tumor lesion is not necessary. Age andgender had no effect on the pharmacokinetics ofrituximab.
Specific Populations
The pharmacokinetics of rituximab products have not been studied in children and adolescents.
No formal studies were conducted to examine the effects of either renal or hepatic impairment
on the pharmacokinetics of rituximab products.
Drug Interaction Studies
Formal drug interaction studies have not been performed with rituximab products.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityNo long-term animal studies have been performed to establish the carcinogenic or mutagenicpotential of rituximab products or to determine potential effects on fertility in males or females.
14 CLINICAL STUDIES
14.1 Relapsed or Refractory, Low-Grade or Follicular, CD20-Positive, B-Cell NHLThe safety and effectiveness of rituximab in relapsed, refractory CD20+ NHL were
demonstrated in 3 single-arm studies enrolling 296 patients.
Study 1
A multicenter, open-label, single-arm study was conducted in 166 patients with relapsed orrefractory, low-grade or follicular, B-cell NHL who received 375 mg/m2 of rituximab given asan intravenous infusion weekly for 4 doses. Patients with tumor masses > 10 cm or with> 5000 lymphocytes/µL in the peripheral blood were excluded from the study.Results are summarized in Table 2. The median time to onset of response was 50 days.
Disease-related signs and symptoms (including B-symptoms) resolved in 64% (25/39) of thosepatients with such symptoms at study entry.
Study 2
In a multicenter, single-arm study, 37 patients with relapsed or refractory, low-grade NHLreceived 375 mg/m2 of rituximab weekly for 8 doses. Results are summarized in Table 2.
Study 3
In a multicenter, single-arm study, 60 patients received 375 mg/m2 of rituximab weekly for4 doses. All patients had relapsed or refractory, low-grade or follicular, B-cell NHL andhad achieved an objective clinical response to rituximab administered 3.8−35.6 months(median 14.5 months) prior to retreatment with rituximab. Of these 60 patients, 5 receivedmore than one additional course of rituximab. Results are summarized in Table 2.
Bulky Disease
In pooled data from studies 1 and 3, 39 patients with bulky (single lesion > 10 cm in diameter) and relapsed or refractory, low-grade NHL received rituximab 375 mg/m2 weekly for 4 doses.
Results are summarized in Table 2.
Table 2
Summary of Rituximab Efficacy Data by Schedule and
Clinical Setting
Study 1
Weekly×4
N=166
Study 2
Weekly×8
N=37
Study 1 and
Study 3
Bulky disease,
Weekly×4
N=39*
Study 3
Retreatment,
Weekly×4
N=60
Overall Response Rate
Complete Response Rate
Median Duration of
Response(Months) [Range] †
, ‡
, §
48%
6%
11.2
[1.9 to 42.1+]
57%
14%
13.4
[2.
