14.2 Previously Untreated, Low-Grade or Follicular, CD20-Positive, B-Cell NHLThe safety and effectiveness of rituximab in previously untreated, low-grade or follicular,CD20+ NHL were demonstrated in 3 randomized, controlled trials enrolling 1,662 patients.
Study 4
A total of 322 patients with previously untreated follicular NHL were randomized (1:1) to receiveup to eight 3-week cycles of CVP chemotherapy alone (CVP) or in combination with rituximab375 mg/m2 on Day 1 of each cycle (R-CVP) in an open-label, multicenter study. The mainoutcome measure of the study was progression-free survival (PFS) defined as the time fromrandomization to the first of progression, relapse, or death.
Twenty-six percent of the study population was >60 years of age, 99% had Stage III or IVdisease, and 50% had an International Prognostic Index (IPI) score ≥2. The results for PFS asdetermined by a blinded, independent assessment of progression are presented in Table 3. Thepoint estimates may be influenced by the presence of informative censoring. The PFS resultsbased on investigator assessment of progression were similar to those obtained by theindependent review assessment.
Table 3
Efficacy Results in Study 4
Study Arm
R-CVP
N=162
CVP
N=160
Median PFS (years) *
Hazard ratio (95% CI) †
2.4
0.44 (0.29, 0.65)
1.4
* p <0.0001, two-sided stratified log-rank test.
† Estimates of Cox regression stratified by center.
Study 5
An open-label, multicenter, randomized (1:1) study was conducted in 1,018 patients withpreviously untreated follicular NHL who achieved a response (CR or PR) to rituximab incombination with chemotherapy. Patients were randomized to rituximab as single-agentmaintenance therapy, 375 mg/m2 every 8 weeks for up to 12 doses or to observation. Rituximabwas initiated at 8 weeks following completion of chemotherapy. The main outcome measure ofthe study was progression-free survival (PFS), defined as the time from randomization in themaintenance/observation phase to progression, relapse, or death, as determined by independentreview.
Of the randomized patients, 40% were ≥60 years of age, 70% had Stage IV disease, 96% hadECOG performance status (PS) 0−1, and 42% had FLIPI scores of 3–5. Prior to randomizationto maintenance therapy, patients had received R-CHOP (75%), R-CVP (22%), or R-FCM (3%);71% had a complete or unconfirmed complete response and 28% had a partial response.
PFS was longer in patients randomized to rituximab as single agent maintenance therapy (HR:0.54, 95% CI: 0.42, 0.70). The PFS results based on investigator assessment of progression weresimilar to those obtained by the independent review assessment.
Figure 1
Kaplan-Meier Plot of IRC

Assessed PFS
Study 6
A total of 322 patients with previously untreated low-grade, B-cell NHL who did not progressafter 6 or 8 cycles of CVP chemotherapy were enrolled in an open-label, multicenter,randomized trial. Patients were randomized (1:1)