Background
Randomized, non-inferiority phase III BRIGHT trial of 447 patients (>18 yr) with indolent CD20+ NHL (FL grade 1/2, lymphoplasmacytic, MZL) or MCL undergoing first-line therapy. Treatment indication required ≥1 of: B-symptoms, large mass, lymphoma-related complications, or hyperviscosity. Excluded: SLL, CLL, FL grade 3.
Interventions and follow up
Arm A (B-R): Bendamustine 90 mg/m2 D1-2 q28d + rituximab 375 mg/m2 D1, 6-8 cycles (n=224).
Arm B: Standard chemoimmunotherapy — R-CHOP (n=104) or R-CVP (n=119), 6-8 cycles (n=223). Maintenance rituximab permitted.
Primary endpoint: Non-inferiority by CR rate (IWG criteria).
mFollow up: 65 months (long-term update).
Arm B: Standard chemoimmunotherapy — R-CHOP (n=104) or R-CVP (n=119), 6-8 cycles (n=223). Maintenance rituximab permitted.
Primary endpoint: Non-inferiority by CR rate (IWG criteria).
mFollow up: 65 months (long-term update).
Results
CR: 31% vs 25% (B-R vs standard); met non-inferiority.
ORR: 97% vs 91%.
5-yr PFS: 65.5% vs 55.8%; HR 0.61; 95% CI 0.45-0.85; P=.0025.
iNHL 5-yr PFS: HR 0.70; 95% CI 0.49-1.01; P=.0582 (favoring B-R).
MCL 5-yr PFS: HR 0.40; 95% CI 0.21-0.75; P=.0035 (favoring B-R).
5-yr OS: 81.7% vs 85%; HR 1.15; 95% CI 0.72-1.84; P=.5461.
Maintenance rituximab (n=197): no OS difference (HR 1.71; 95% CI 0.62-4.72; P=.2973).
ORR: 97% vs 91%.
5-yr PFS: 65.5% vs 55.8%; HR 0.61; 95% CI 0.45-0.85; P=.0025.
iNHL 5-yr PFS: HR 0.70; 95% CI 0.49-1.01; P=.0582 (favoring B-R).
MCL 5-yr PFS: HR 0.40; 95% CI 0.21-0.75; P=.0035 (favoring B-R).
5-yr OS: 81.7% vs 85%; HR 1.15; 95% CI 0.72-1.84; P=.5461.
Maintenance rituximab (n=197): no OS difference (HR 1.71; 95% CI 0.62-4.72; P=.2973).
Adverse events
Hematologic (grade 3-4, B-R vs R-CHOP vs R-CVP): neutropenia 39% vs 87% vs 49%.
Infections: 12% vs 5% vs 7%.
Other: drug hypersensitivity 3% vs 0% vs 2%; fatigue 4% vs 2% vs 3%.
Second malignancy (excl. NHL, non-melanoma skin): 22/224 (B-R) vs 13/223 (standard).
Infections: 12% vs 5% vs 7%.
Other: drug hypersensitivity 3% vs 0% vs 2%; fatigue 4% vs 2% vs 3%.
Second malignancy (excl. NHL, non-melanoma skin): 22/224 (B-R) vs 13/223 (standard).
Conclusions
B-R was non-inferior to R-CHOP/R-CVP for CR with similar ORR; in the 5-year update B-R showed superior PFS (notably in MCL) but no OS advantage, with a distinct toxicity profile.
Key Limitations
Mixed standard-arm comparator (R-CHOP and R-CVP) and a numerically higher second-malignancy count with B-R complicate interpretation. PFS benefit did not translate to OS, and the trial was powered for CR non-inferiority rather than survival.
Clinical Context
BRIGHT corroborates StiL, supporting B-R as a preferred first-line regimen for indolent and mantle cell NHL per ASCO/ESMO guidance.
Long-term update: Flinn IW et al, JCO, 2019; PMID: 30811293, link.
Standard-arm regimens: R-CHOP (rituximab 375, cyclophosphamide 750, doxorubicin 50, vincristine 1.4 mg/m2 D1, prednisone 100 mg D1-5, q21d) or R-CVP (rituximab + cyclophosphamide 1000, vincristine 1.4 mg/m2, prednisone 100 mg D1-5).
Long-term update: Flinn IW et al, JCO, 2019; PMID: 30811293, link.
Standard-arm regimens: R-CHOP (rituximab 375, cyclophosphamide 750, doxorubicin 50, vincristine 1.4 mg/m2 D1, prednisone 100 mg D1-5, q21d) or R-CVP (rituximab + cyclophosphamide 1000, vincristine 1.4 mg/m2, prednisone 100 mg D1-5).