Treatment of Cerebral Histiocytosis With Low Dose of Cobimetinib: A Report of 2 Cases
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Treatment of Cerebral Histiocytosis With Low Dose of Cobimetinib: A Report of 2 Cases. / Schubert, Charlotte; Schiffmann, Insa; Farschtschi, Said C; Emile, Jean-François; Friese, Manuel A.
In: NEUROL-NEUROIMMUNOL, Vol. 11, No. 3, 05.2024, p. e200233.Research output: SCORING: Contribution to journal › Case report › Research › peer-review
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TY - JOUR
T1 - Treatment of Cerebral Histiocytosis With Low Dose of Cobimetinib: A Report of 2 Cases
AU - Schubert, Charlotte
AU - Schiffmann, Insa
AU - Farschtschi, Said C
AU - Emile, Jean-François
AU - Friese, Manuel A
PY - 2024/5
Y1 - 2024/5
N2 - OBJECTIVES: Histiocytic disorders are pathologic expansions of myeloid cells in multiple organs, including the CNS. They share activation of the MAP kinase pathway due to either BRAFV600E variant or other variants in the RAS-RAF-MEK-ERK pathway. The rarity and heterogeneity of the disease only enable therapy through pathophysiologic considerations.METHODS: We present 2 histiocytosis cases without BRAF sequence variants that affect the CNS, one with Erdheim-Chester disease and the other with an unspecified histiocytosis, and their diagnostic and therapeutic challenges.RESULTS: In both cases, comprehensive analysis of the RAS-RAF-MEK-ERK signaling pathway secured the diagnosis. Treatment with the MEK inhibitor cobimetinib brought the disease to a complete halt. However, side effects such as thrombosis and serous macular edema made it necessary to reduce cobimetinib dosage. Low-dose cobimetinib maintenance medication was successful in preventing recurrence of histiocytic disease.DISCUSSION: CNS involvement of histiocytic disorders can lead to detrimental neurologic symptoms. MEK inhibitors are effective treatment options for some of these patients. Since side effects are common, according to our cases we propose a low-dose treatment of 20 mg per day to balance treatment effects with side effects.CLASSIFICATION OF EVIDENCE: This case report provides Class IV evidence. This is a single observational study without controls.
AB - OBJECTIVES: Histiocytic disorders are pathologic expansions of myeloid cells in multiple organs, including the CNS. They share activation of the MAP kinase pathway due to either BRAFV600E variant or other variants in the RAS-RAF-MEK-ERK pathway. The rarity and heterogeneity of the disease only enable therapy through pathophysiologic considerations.METHODS: We present 2 histiocytosis cases without BRAF sequence variants that affect the CNS, one with Erdheim-Chester disease and the other with an unspecified histiocytosis, and their diagnostic and therapeutic challenges.RESULTS: In both cases, comprehensive analysis of the RAS-RAF-MEK-ERK signaling pathway secured the diagnosis. Treatment with the MEK inhibitor cobimetinib brought the disease to a complete halt. However, side effects such as thrombosis and serous macular edema made it necessary to reduce cobimetinib dosage. Low-dose cobimetinib maintenance medication was successful in preventing recurrence of histiocytic disease.DISCUSSION: CNS involvement of histiocytic disorders can lead to detrimental neurologic symptoms. MEK inhibitors are effective treatment options for some of these patients. Since side effects are common, according to our cases we propose a low-dose treatment of 20 mg per day to balance treatment effects with side effects.CLASSIFICATION OF EVIDENCE: This case report provides Class IV evidence. This is a single observational study without controls.
U2 - 10.1212/NXI.0000000000200233
DO - 10.1212/NXI.0000000000200233
M3 - Case report
C2 - 38588479
VL - 11
SP - e200233
JO - NEUROL-NEUROIMMUNOL
JF - NEUROL-NEUROIMMUNOL
SN - 2332-7812
IS - 3
ER -
