Clinical Outcomes and Molecular Responses in Children with Langerhans Cell Histiocytosis Treated with MAPK Pathway Inhibitors

Conclusions: MAPK pathway inhibitors may be a relatively safe salvage therapy for refractory systemic LCH and LCH-ND but the efficacy and durability of responses with this strategy remains to be delineated. Children with relapsed/refractory high-risk LCH who were at the highest risk of death from disease generally benefited from this strategy. Patients with longstanding neurodegenerative disease seem to have the least benefit from MAPK inhibitors. However, patients with relatively early onset neurodegenerative disease, especially without clinical manifestations, seem to have the greatest benefit. While the presence of persistent BRAF-V600E+ circulating cells appears to be associated with risk of relapse and type of LCH organ involvement, quantifiable changes in these levels did not consistently correlate with clinical disease activity or response (in contrast to those treated with chemotherapy). We hypothesize that inhibition of the MAPK pathway may confer clinical benefit by blocking differentiation and proliferation of lesions, but may not have cytotoxic effect on precursor cells. This is supported by the observation that MAPK regulates lesion progression by inhibiting CCR7 expression, thereby blocking emigration of LCH cells from the lesion. Persistence of BRAF-V600E+ mononuclear cells in blood and bone marrow even in patients with impressive clinical responses may underlie the high rates of eventual progression/relapse with this type of treatment. Future prospective trial...
Source: Blood - Category: Hematology Authors: Tags: 201. Granulocytes, Monocytes, and Macrophages: Poster III Source Type: research