Hairy cell leukemia (HCL) is a B-cell malignancy for which purine nucleoside analogs have been highly effective but can cause prolonged myelosuppression and immunosuppression. Targeted therapy against mutant BRAF with vemurafenib in combination with the anti-CD20 antibody rituximab has demonstrated efficacy in HCL. Traditional vemurafenib dosing (960 mg twice daily) is frequently associated with dose reductions. The present observational study assessed a low-dose vemurafenib strategy combined with rituximab — the Scripps regimen — aiming to maintain activity while improving tolerability.
This was a prospective observational study reported in Blood Advances. Fifteen adult patients with either treatment-naïve (frontline) or relapsed/refractory HCL were enrolled. The relapsed/refractory subgroup had a median of one prior therapy. The source abstract and figures provide cohort-level data on response, hematologic recovery, marrow assessments, and safety; additional granular baseline characteristics beyond what is summarized in the abstract were not reported in the source.
The regimen consisted of oral vemurafenib at 240 mg twice daily for 8 weeks concurrently with intravenous rituximab 375 mg/m2 every 2 weeks for a total of 8 doses. Rituximab was started at the same time as vemurafenib and continued for three additional doses after vemurafenib completion, giving a total treatment duration with rituximab of 14 weeks. The study figures include a treatment schema showing continuous low-dose vemurafenib for 8 weeks with rituximab dosing every 2 weeks.
All 15 patients achieved complete hematologic recovery. Platelet recovery to >100 × 10^3/μL occurred at a median of 15 days. Neutrophil recovery to >1.0 × 10^3/μL occurred at a median of 29 days. Figure 2 in the source documents the time course of key hematologic parameters: white blood cell count, absolute neutrophil count (ANC), platelet count, and hemoglobin over the initial 84 days, showing early platelet increases by day 28 and a steady ANC rise.
The overall response rate was 87%. Eleven patients (73%; 95% CI, 48–89) achieved complete response (CR) and two achieved partial responses. Minimal residual disease (MRD) negativity at 6 months was documented in 8 patients (53%; 95% CI, 27–79). In predefined subgroups, frontline patients (n = 7) had 6 CRs (86%; 95% CI, 42–100) and 4 were MRD-negative (57%; 95% CI, 18–90). Relapsed or refractory patients (n = 8; median 1 prior therapy) had 5 CRs (63%; 95% CI, 24–91) and 4 were MRD-negative (50%; 95% CI, 16–84). Marrow cellularity and MRD status before and after treatment are presented in figure format in the source, showing reductions in marrow involvement and several patients achieving IHC and flow-based MRD negativity.
The regimen demonstrated favorable tolerability in this cohort. No grade 3 to 4 toxicities or deaths were reported in the 15 patients. The abstract and figures emphasize the absence of severe toxicities with the low-dose vemurafenib plus rituximab schedule; specific lower-grade adverse event details or laboratory toxicity listings beyond hematologic recovery were not provided in the abstract.
At a median follow-up of 18 months, the median progression-free survival (PFS) was not reached. One patient experienced disease progression at 20 months. These outcome metrics come from the study abstract; longer-term durability and survival outcomes beyond the reported median follow-up were not included in the source.
In this prospective observational cohort of 15 adults with untreated or relapsed/refractory HCL, the Scripps low-dose vemurafenib plus rituximab regimen induced rapid hematologic recovery, a high overall response rate (87%), and a 73% CR rate, with over half of patients MRD-negative at 6 months. The regimen was well tolerated with no grade 3–4 toxicities or deaths reported. The authors report that low-dose vemurafenib combined with rituximab provides a potentially effective and better-tolerated targeted approach for HCL patients, including those who are frontline or relapsed/refractory. The abstract does not report extended safety detail, quality-of-life measures, or comparisons with standard-dose vemurafenib or purine nucleoside analogs.
This trial is registered at ClinicalTrials.gov as NCT05388123. The authors declared no competing financial interests in the conflict-of-interest statement. The full text and figures are available via PubMed Central (PMCID PMC13495371) for additional methodological and result details not fully summarized in the abstract.