Acalabrutinib+Lenalidomide+Rituximab (BTK+IMiD+CD20) Hits 92% CR in Frontline High-Burden FL

Acalabrutinib (BTK inhibitor) plus lenalidomide (IMiD) and rituximab (anti-CD20) was tested first-line in a single-arm phase II for advanced-stage follicular lymphoma with high tumor burden (n=24; NCT04404088; median follow-up 43 months). Best ORR was 100% with 92% CR; CR at 30 months (CR30) 65% and POD24 17%; 2-yr PFS 79% and 2-yr OS 92%, medians not reached; grade≥3 AEs included neutropenia 58% and LFT elevation 17%. These outcomes sit within established frontline benchmarks—3-yr PFS ~77–78% with R2 and 80.0% vs 73.3% (HR 0.66) with obinutuzumab- vs rituximab-chemo—while the triplet’s grade≥3 neutropenia (58%) resembles chemo (≈50%) more than R2 alone (≈32%); acalabrutinib is not FDA-approved for FL in the US.