Search

BRAFV600E is the key oncogenic driver mutation in hairy cell leukemia (HCL). We report the efficacy and safety of dabrafenib plus trametinib in patients with relapsed/refractory BRAFV600E mutation–positive HCL. This open-label, phase 2 study enrolled patients with BRAFV600E mutation–positive HCL refractory to first-line treatment with a purine analog or relapsed after ≥2 prior lines of treatment. Patients received dabrafenib 150 mg twice daily plus trametinib 2 mg once daily until disease progression, unacceptable toxicity, or death. The primary endpoint was investigator-assessed objective response rate (ORR) per criteria adapted from National Comprehensive Cancer Network-Consensus Resolution guidelines. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Fifty-five patients with BRAFV600E mutation–positive HCL were enrolled. The investigator-assessed ORR was 89.0% (95% confidence interval, 77.8%-95.9%); 65.5% of patients had a complete response (without minimal residual disease [MRD]: 9.1% [negative immunohistochemistry of bone marrow {BM} biopsy], 12.7% [negative BM aspirate flow cytometry {FC}], 16.4% [negative immunohistochemistry and/or FC results]; with MRD, 49.1%), and 23.6% had a partial response. The 24-month DOR was 97.7% with 24-month PFS and OS rates of 94.4% and 94.5%, respectively. The most common treatment-related adverse events were pyrexia (58.2%), chills (47.3%), and hyperglycemia (40.0%). Dabrafenib plus trametinib demonstrated durable responses with a manageable safety profile consistent with previous observations in other indications and should be considered as a rituximab-free therapeutic option for patients with relapsed/refractory BRAFV600E mutation–positive HCL. This trial is registered at www.clinicaltrials.govas #NCT02034110.

Hairy cell leukemia is a rare, indolent, B-cell lymphoproliferative disease characterized by the BRAFV600E mutation in 90% to 100% of patients. Few treatment options are available for patients who progress on first-line therapy with a purine analogue and/or rituximab. The efficacy of combined BRAF and MEK inhibition is well established in BRAFV600-mutated melanoma, non-small cell lung cancer, and anaplastic thyroid cancer. Here we report interim results of treatment with the combination of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) in patients with recurrent/refractory BRAFV600E-mutated HCL.