Background
Phase III RCT. 379 patients aged 18–59 years with previously untreated DLBCL and aaIPI 1–3 (high-risk). Conducted by GELA. Designed to determine whether the intensive R-ACVBP regimen with sequential consolidation could improve outcomes over R-CHOP in younger high-risk DLBCL patients.
Interventions and follow up
Arm A: R-ACVBP (rituximab 375 mg/m² D1 + doxorubicin 75 mg/m² + cyclophosphamide 1,200 mg/m² + vindesine 2 mg/m² D1,5 + bleomycin 10 mg D1,5 + prednisolone 60 mg/m² D1–5) × 4 cycles q14d, then sequential consolidation: high-dose MTX ×2, cytarabine, etoposide-ifosfamide
Arm B: R-CHOP-21 × 8 cycles (standard reference)
Primary endpoint: Event-free survival (EFS) at 2 years
Median follow up: 44 months
Arm B: R-CHOP-21 × 8 cycles (standard reference)
Primary endpoint: Event-free survival (EFS) at 2 years
Median follow up: 44 months
Results
2-year EFS (primary): 60.6% (R-ACVBP) vs 48.4% (R-CHOP) — HR 0.73, 95% CI 0.56–0.96, P=.0023
3-year OS: 81.4% vs 76.0% — HR 0.71, 95% CI 0.50–1.00, P=.044
ORR: 92% vs 92%
3-year OS: 81.4% vs 76.0% — HR 0.71, 95% CI 0.50–1.00, P=.044
ORR: 92% vs 92%
Adverse events
Hematologic/infectious (grade ≥3): Febrile neutropenia 36% (R-ACVBP) vs 21% (R-CHOP); infections 23% vs 14%
Mucosal (grade ≥3): Mucositis 19% vs 7%
Mortality/hospitalization: Treatment-related mortality 5% vs 4%; significantly more treatment-related hospitalizations with R-ACVBP
Mucosal (grade ≥3): Mucositis 19% vs 7%
Mortality/hospitalization: Treatment-related mortality 5% vs 4%; significantly more treatment-related hospitalizations with R-ACVBP
Conclusions
R-ACVBP with sequential consolidation significantly improved EFS and OS over R-CHOP in younger high-risk DLBCL, at the cost of substantially greater toxicity. Established R-ACVBP as a preferred regimen in France but did not achieve widespread international adoption.
Key Limitations
Higher R-ACVBP toxicity — including 5% treatment-related mortality — limits broad adoption. Enrolled only younger patients (18–59y) with high-risk aaIPI; not applicable to elderly or low-risk DLBCL. No molecular subtyping (GCB vs ABC); effect may differ by cell-of-origin. The consolidation schedule requires specialized infrastructure.
Clinical Context
R-ACVBP is incorporated into French LYSA guidelines as a preferred option for young high-risk DLBCL. Outside France, R-CHOP remains standard (ESMO) due to its more favorable toxicity profile. Subsequent LYSA trials (GAINED) built on R-ACVBP as a backbone for intensification.
References