Comment on: Langerhans cell histiocytosis with BRAF p.N486_P490del or MAP2K1 p.K57_G61del treated by the MEK inhibitor trametinib

Success of Trametinib in the Treatment of Langerhans Cell Histiocytosis With Novel MAPK Pathway Mutations

“…After the discovery of a MAP2K1 Q56P point mutation, a daily regimen of trametinib was initiated, and the patient experienced complete resolution of his skeletal lesions with no adverse effects. 11 Messinger et al 12 also noted that trametinib was successful in treating a 2-year-old patient with multisystem LCH and a MAP2K1 p.K57_G61del in parallel with a course of corticosteroids. This patient experienced complete resolution of disease after 22 months with minimal adverse effects.…”

“…Daily therapy with trametinib has been utilized to achieve complete remission of disease in several LCH patients with varying MAP2K1 mutations. For example, Vicenzi and Ray11 described the successful treatment of a 4-year-old patient with multisystem, treatment-refractory LCH with trametinib. After the discovery of a MAP2K1 Q56P point mutation, a daily regimen of trametinib was initiated, and the patient experienced complete resolution of his skeletal lesions with no adverse effects 11.…”

“…For example, Vicenzi and Ray11 described the successful treatment of a 4-year-old patient with multisystem, treatment-refractory LCH with trametinib. After the discovery of a MAP2K1 Q56P point mutation, a daily regimen of trametinib was initiated, and the patient experienced complete resolution of his skeletal lesions with no adverse effects 11. Messinger et al12 also noted that trametinib was successful in treating a 2-year-old patient with multisystem LCH and a MAP2K1 p.K57_G61del in parallel with a course of corticosteroids.…”

“…9 Several case reports have described complete or partial responses to a daily regimen of trametinib in patients with multifocal or multisystem LCH and various MAPK pathway mutations, including point mutations and deletions in MEK (Table, Supplemental Digital Content 2, http://links.lww.com/JPHO/A588 which summarizes the MAPK pathway mutations discussed and their response to trametinib). [10][11][12] In addition, a retrospective cohort study of 21 pediatric LCH patients with progression or recurrence of disease who were treated with some type of MAPK pathway inhibitor revealed an overall response rate of 86%. 13 Furthermore, only 19% of patients demonstrated a grade III or IV toxicity, and no treatment-related mortality was reported, contrasting with the high risk of mortality associated with the traditional salvage therapies used for refractory or relapsed LCH, including high-dose chemotherapy or hematopoietic stem cell transplantation.…”

“…It is relatively well-tolerated, as the most common side effects are rash and diarrhea 9. Several case reports have described complete or partial responses to a daily regimen of trametinib in patients with multifocal or multisystem LCH and various MAPK pathway mutations, including point mutations and deletions in MEK (Table, Supplemental Digital Content 2, http://links.lww.com/JPHO/A588 which summarizes the MAPK pathway mutations discussed and their response to trametinib) 10–12. In addition, a retrospective cohort study of 21 pediatric LCH patients with progression or recurrence of disease who were treated with some type of MAPK pathway inhibitor revealed an overall response rate of 86% 13.…”