Background
Open-label, multicenter phase III PRIMA trial enrolled 1,217 patients with previously untreated high-tumor-burden follicular lymphoma (grade ≤3a) responding to first-line immunochemotherapy. Patients achieving CR/PR were randomized to 2 years of rituximab maintenance versus observation. Excluded: FL grade 3b, transformation to DLBCL, CNS involvement.
Interventions and follow up
Arm A: Rituximab 375 mg/m2 every 8 weeks for 2 years (n=505), starting 8 weeks after induction (R-CHOP, R-CVP, or R-FCM, center-selected).
Arm B: Observation (n=513).
Primary endpoint: PFS.
mFollow up: 36 months (primary); 9 years (long-term update).
Arm B: Observation (n=513).
Primary endpoint: PFS.
mFollow up: 36 months (primary); 9 years (long-term update).
Results
3-yr PFS: 74.9% vs 57.6% (maintenance vs observation); HR 0.55; 95% CI 0.44-0.68; P<.0001.
mPFS (long-term): 10.5 vs 4.1 years; HR 0.61; 95% CI 0.52-0.73; P<.001.
OS: no difference (~80%); HR 1.04; 95% CI 0.77-1.40; P=.7948.
Death: 17.4% vs 16.4%; most common cause progressive disease (51.1% vs 47.6%) and solid tumors (5.7% vs 20.2%).
mPFS (long-term): 10.5 vs 4.1 years; HR 0.61; 95% CI 0.52-0.73; P<.001.
OS: no difference (~80%); HR 1.04; 95% CI 0.77-1.40; P=.7948.
Death: 17.4% vs 16.4%; most common cause progressive disease (51.1% vs 47.6%) and solid tumors (5.7% vs 20.2%).
Adverse events
Overall (grade 3-4, maintenance vs observation): 24% vs 17%.
Hematologic: grade 3-4 neutropenia 4% vs 1%.
Infections: grade 3-4 infections 4% vs 1%.
Overall: rituximab maintenance was generally well tolerated; the modest excess in cytopenias and infections did not increase non-relapse mortality.
Hematologic: grade 3-4 neutropenia 4% vs 1%.
Infections: grade 3-4 infections 4% vs 1%.
Overall: rituximab maintenance was generally well tolerated; the modest excess in cytopenias and infections did not increase non-relapse mortality.
Conclusions
Two years of rituximab maintenance after first-line immunochemotherapy significantly and durably improves PFS in high-tumor-burden follicular lymphoma, without an OS benefit and with modest added toxicity.
Key Limitations
The PFS benefit did not translate into an OS advantage even at 9 years. Induction regimen was center-selected (not randomized), introducing heterogeneity. The optimal maintenance schedule and the trade-off of prolonged immunosuppression versus delayed progression remain debated.
Clinical Context
PRIMA established 2-year rituximab maintenance as a standard option after first-line immunochemotherapy for high-tumor-burden FL per ASCO/ESMO guidance, with the durable benefit confirmed in the long-term (Bachy et al, JCO, 2019; PMID: 31339826).