Chemotherapy-Free Treatment of Classical Hairy Cell Leukemia

Classical hairy cell leukemia (HCL) is characterized in virtually all cases by the BRAF V600E mutation and has been shown to be highly responsive to the BRAF inhibitor vemurafenib in the relapsed setting (NEJM JW Oncol Hematol 2021 Jun 4 and N Engl J Med 2021 May 13; 384:1810).

Investigators have now conducted an industry- and grant-funded, multicenter, phase 2 trial of vemurafenib for previously untreated classical HCL patients with cytopenias. Patients received vemurafenib (960 mg orally twice daily for four 28-day cycles) plus obinutuzumab (1000 mg intravenously on days 1, 8, and 15 of cycle 2 and on day 1 of cycles 3 and 4). Restaging abdominal CT scans and bone marrow biopsies were performed following cycle 4. Residual marrow involvement from HCL was identified by multicolor flow cytometry and immunohistochemistry. The primary endpoint was complete remission, defined as improvement in cytopenias to an absolute neutrophil count of ≥1500/mm³, a platelet count of ≥100,000/mm³, and a hemoglobin level of ≥11 gm.

Among 30 patients, the 27 (90%) who completed four treatment cycles achieved complete remission; the remaining three discontinued treatment early due to rash, pneumonia, or verrucous hyperplasia. Twenty-six patients (96%) had undetectable measurable residual disease by multicolor flow cytometry at the end of cycle 4. Most patients had improvement in cytopenias during cycle 1 and before initiation of obinutuzumab. Progression-free survival was 97% at 24 and 36 months. One death was related to multifocal pneumonia. The most common vemurafenib-related adverse effects (AEs) were rash in 93% of patients and arthralgias in 80%; AEs were managed by dose reductions in 96% of affected patients.