Background
Phase III, randomized, placebo-controlled trial. Higher-risk R/R FL patients after ≥2 prior lines. Tafasitamab is an Fc-enhanced anti-CD19 monoclonal antibody (approved with lenalidomide for R/R DLBCL). inMIND tested tafasitamab + lenalidomide + rituximab (T+R²) versus rituximab + lenalidomide (R²) alone in R/R FL, leveraging dual CD19 (tafasitamab) + CD20 (rituximab) targeting with lenalidomide immunomodulation.
Interventions and follow up
Arm A: Tafasitamab 12mg/kg IV (days 1, 8, 15, 22 cycle 1; days 1, 8 cycles 2–3; day 1 cycles 4+) + lenalidomide 20mg PO days 1–21 q28d × 12 cycles + rituximab 375mg/m² IV day 1 q4w × 12 doses
Arm B: Placebo IV + lenalidomide 20mg PO days 1–21 + rituximab 375mg/m² IV (same schedule)
Primary endpoint: Progression-free survival (independent review committee)
mFollow up: ~24 months
Arm B: Placebo IV + lenalidomide 20mg PO days 1–21 + rituximab 375mg/m² IV (same schedule)
Primary endpoint: Progression-free survival (independent review committee)
mFollow up: ~24 months
Results
PFS (primary): mPFS not reached (T+R²) vs 11.6 months (R²), HR 0.43, 95% CI 0.31–0.60, P<.001
2-year PFS rate: 58.5% vs 35.7%
CR rate: 58.5% vs 38.5%
ORR: 83.2% vs 70.3%
2-year PFS rate: 58.5% vs 35.7%
CR rate: 58.5% vs 38.5%
ORR: 83.2% vs 70.3%
Adverse events
Overall/hematologic: Grade ≥3 AEs 70.4% vs 61.3%; grade ≥3 neutropenia 37.3% vs 27.7%; grade ≥3 infections 18.9% vs 13.3%
Infusion/discontinuation: Infusion-related reactions any grade 34.0% vs 27.7%; treatment discontinuation due to AEs 12.5% vs 9.3%
Infusion/discontinuation: Infusion-related reactions any grade 34.0% vs 27.7%; treatment discontinuation due to AEs 12.5% vs 9.3%
Conclusions
Adding tafasitamab to R² (T+R²) significantly improved PFS versus R² alone in R/R FL (HR 0.43), establishing tafasitamab's activity in FL and representing the first positive Phase III trial of a CD19-directed antibody in FL.
Key Limitations
The comparator arm was R² (already a chemotherapy-free doublet), not single-agent rituximab or chemoimmunotherapy — making the absolute benefit over standard options more modest. Grade ≥3 neutropenia substantially increased with the triplet (37% vs 28%). OS data immature. No comparison to epcoritamab + R² (EPCORE FL-1), which showed a more striking HR 0.21 — it is unclear whether T+R² or epcoritamab + R² is superior. Tafasitamab is not yet approved for FL (approved only for DLBCL).
Clinical Context
Published in Lancet 2026 alongside EPCORE FL-1 — both trials transform the R/R FL landscape. FDA approval of tafasitamab for FL is pending as of early 2026. T+R² provides an all-IV/oral combination without the step-up hospitalization requirements of bispecific antibodies, potentially offering logistical advantages. Together, EPCORE FL-1 and inMIND establish the triplet bispecific/anti-CD19 + R² strategy as the emerging standard for R/R FL, with ongoing uncertainty about sequencing versus CAR-T.