Low-dose vemurafenib (BRAF V600E inhibitor) + rituximab drives 73% CR with zero grade 3-4 AEs in HCL

Vemurafenib is an oral BRAF inhibitor (active in BRAF V600E–mutant classic HCL) and rituximab is an anti-CD20 monoclonal antibody; in this prospective observational “Scripps regimen” study, patients received vemurafenib 240mg BID for 8 weeks plus rituximab 375mg/m² IV q2w for 8 doses in treatment-naïve or relapsed/refractory HCL (n=15; front-line n=7; R/R n=8 with median 1 prior therapy; NCT05388123). ORR was 87% with 11 CRs (73%) and 2 PRs, and MRD-negativity at 6 months in 53% overall (front-line: CR 86%, MRD− 57%; R/R: CR 63%, MRD− 50%); counts recovered quickly (median 15 days to platelets >100k/µL; 29 days to ANC >1.0k/µL) and at median 18-month follow-up only 1 progression occurred (at 20 months; median PFS not reached). Safety looked notably “clean” here (no grade 3-4 toxicities or deaths), which contrasts with purine analog–based standards (e.g., cladribine ± rituximab) that typically deliver very high CR/MRD-negative rates but at the cost of clinically meaningful myelosuppression/immunosuppression, and also contrasts with historical full-dose vemurafenib strategies that often require dose reductions.