Low-dose vemurafenib plus rituximab in frontline and relapsed or refractory hairy cell leukemia: the Scripps regimen

Purine nucleoside analogs are highly effective in the treatment of hairy cell leukemia (HCL) but are associated with myelosuppression and immunosuppression. Targeted therapy with the BRAF inhibitor vemurafenib in combination with the anti-CD20 antibody rituximab has shown marked efficacy, but traditional dosing of vemurafenib (960 mg twice daily) requires frequent dose reductions. We conducted a prospective observational study of low-dose vemurafenib (240 mg twice daily orally for 8 weeks) plus rituximab (375 mg/m2 IV every 2 weeks for 14 weeks, 8 total doses) in adults with treatment-naïve or relapsed/refractory HCL. Fifteen patients were enrolled. All achieved complete hematologic recovery, with normalization of thrombocytopenia (platelet count >100 × 103/μL) and neutropenia (neutrophil count >1.0 × 103/μL) at a median of 15 and 29 days, respectively. The overall response rate was 87%, including 11 complete responses (CRs; 73%; 95% confidence interval [CI], 48-89) and 2 partial responses, with 8 patients (53%; 95% CI, 27-79) achieving minimal residual disease (MRD) negativity at 6 months. Frontline patients (n = 7) had 6 CRs (86%; 95% CI, 42-100) and 4 were MRD-negative (57%; 95% CI, 18-90), whereas relapsed/refractory patients (n = 8; median of 1 prior therapy) had 5 CRs (63%; 95% CI, 24-91) and 4 were MRD-negative (50%; 95% CI, 16-84). At a median follow-up of 18 months, 1 patient progressed at 20 months; median progression-free survival was not reached. No grade 3 to 4 toxicities or deaths occurred. Low-dose vemurafenib combined with rituximab induced rapid hematologic recovery and favorable tolerability in patients with both untreated and relapsed/refractory HCL. This trial was registered at www.clinicaltrials.gov as NCT05388123.