Treatment options for patients with hairy cell leukaemia (HCL) progressing after first-line therapy are limited. Results from a phase 2 study recently published in Blood, show that the combination of dabrafenib plus trametinib induces durable responses and manageable safety profile in patients with relapsed/refractory BRAF V600E mutation-positive HCL. These results suggest that this regimen should be considered as a rituximab-free therapeutic option for these patients.
Hairy cell leukaemia (HCL) is a rare, indolent B-cell lymphoproliferative disease usually associated with pancytopenia and splenomegaly. The recommended first-line treatment for patients with HCL consists of purine analogues with or without rituximab. Unfortunately, treatment options for patients progressing after first-line therapy remain limited. Notably, mutations in the BRAF (primarily V600E) gene are observed in 90% to 100% of patients with HCL. Combining BRAF and MEK inhibition has already shown successful results in other tumours, such as BRAF V600E-mutated melanoma, non-small cell lung cancer, and anaplastic thyroid cancer. However, data in patients with HCL are lacking. This phase 2 study evaluated dabrafenib plus trametinib treatment in patients with BRAF V600E mutation-positive rare cancers.
This phase 2 study enrolled 55 patients with BRAF V600E mutation-positive HCL refractory to first-line treatment with a purine analogue 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 of the study was objective response rate (ORR), with secondary objectives including duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
After a median follow-up of 43.2 months, the ORR was reported at 89.1% . Overall, 36 patients (65.5%) achieved a complete response, of whom 9 patients obtained minimal residual disease (MRD) negativity. In addition, 13 patients (23.6%) achieved partial response, 4 (7.3%) had a minor response, and 1 (1.8%) had progressive disease as the best overall response. The 24-month DOR was reported at 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 hyperglycaemia (40.0%).
In conclusion, dabrafenib plus trametinib demonstrated durable responses with a manageable safety profile in patients with progressive BRAF-mutant HCL. Therefore, this regimen should be considered as a rituximab-free salvage option for patients with relapsed/refractory BRAF V600E mutation–positive HCL.