Background
Phase III, open-label RCT. 249 patients aged ≥80 or 70–79 with contraindication to standard CHOP with newly diagnosed DLBCL. R-miniCHOP (rituximab + reduced-dose CHOP) was established as the reference regimen for very elderly patients. SEXIE-R-CHOP tested adding lenalidomide to R-miniCHOP in this frail population.
Interventions and follow up
Arm A: R²-miniCHOP — rituximab 375mg/m² IV day 1 + cyclophosphamide 400mg/m² IV day 1 + doxorubicin 25mg/m² IV day 1 + vincristine 1mg IV day 1 + prednisone 40mg/m² PO days 1–5 + lenalidomide 10mg PO days 1–14, q21d × 6 cycles
Arm B: R-miniCHOP — same backbone without lenalidomide, q21d × 6 cycles
Primary endpoint: 2-year overall survival
Median follow-up: 38.8 months
Arm B: R-miniCHOP — same backbone without lenalidomide, q21d × 6 cycles
Primary endpoint: 2-year overall survival
Median follow-up: 38.8 months
Results
2-year OS: 57.7% vs 54.1%, HR 0.85, 95% CI 0.59–1.24, P=.41 — not significant
2-year PFS: 51.5% vs 44.3%, HR 0.82, 95% CI 0.58–1.16 — not significant
ORR: 71.9% vs 67.8% — not significant
CR rate: 60.6% vs 55.0%
2-year PFS: 51.5% vs 44.3%, HR 0.82, 95% CI 0.58–1.16 — not significant
ORR: 71.9% vs 67.8% — not significant
CR rate: 60.6% vs 55.0%
Adverse events
Overall: Grade ≥3 AEs 87.5% (R²-miniCHOP) vs 79.2% (R-miniCHOP); treatment discontinuation 23.3% vs 15.8%
Hematologic: Grade ≥3 neutropenia 65.0% vs 49.2%; febrile neutropenia 23.3% vs 14.2%
Infectious: Grade ≥3 infections 27.5% vs 17.5%
Hematologic: Grade ≥3 neutropenia 65.0% vs 49.2%; febrile neutropenia 23.3% vs 14.2%
Infectious: Grade ≥3 infections 27.5% vs 17.5%
Conclusions
Adding lenalidomide to R-miniCHOP did not improve OS or PFS in very elderly DLBCL patients. The negative result mirrors ROBUST and PHOENIX, reinforcing that R-CHOP backbone intensification strategies have consistently failed in DLBCL regardless of biological subtype selection.
Key Limitations
Trial was not biomarker-selected — lenalidomide benefit, if any, may require ABC/non-GCB enrichment. Increased toxicity without benefit raises concern about harm in this frail population. Modest sample size may be underpowered for the absolute OS difference observed. Functional status and CIRS comorbidity scores were heterogeneous.
Clinical Context
R-miniCHOP remains standard of care for patients ≥80 or unfit elderly DLBCL, established by the LNH03-7B trial (Peyrade, Lancet Oncol 2011). SEXIE does not change this standard, and no approved augmentation exists for this population. ESMO and ASCO guidance continue to support reduced-intensity immunochemotherapy in frail elderly DLBCL.