Vemurafenib (Zelboraf) for BRAF V600E positive Erdheim-Chester Disease (ECD)

Vemurafenib (Zelboraf) for BRAF V600E positive Erdheim-Chester Disease (ECD)

Last Updated on December 21, 2017 by Joseph Gut – thasso

Dezember 21, 2017 – Erdheim–Chester disease ((ECD), also known as Erdheim–Chester syndrome or polyostotic sclerosing histiocytosis) is a form of a bone marrow borne blood cancer. It is a rare disease characterized by the abnormal multiplication of a specific type of white blood cells called histiocytes, or tissue macrophages, and is technically termed a non-Langerhans-cell histiocytosis). The disease involves an infiltration of lipid-laden macrophages, multinucleated giant cells, an inflammatory infiltrate of lymphocytes and histiocytes in the bone marrow, and a generalized sclerosis of the long bones. Generally, patients with ECD have very limited life expectancies.
By its very recent approval, the American Food & Drug Administration (FDA) FDA has now expanded the indication of Vemurafenib (Zelboraf) to also treat selected adult patients with Erdheim-Chester Disease. Vemurafenib (Zelboraf) was first approved in 2011 to treat selected patients with melanoma that harbor the BRAF V600E mutation, with its expansion of indication, FDA brings now likewise Vemurafenib (Zelboraf)and to patients with Erdheim Chester disease who are BRAF V600E positive, making Vemurafenib (Zelboraf) the first treatment approved for selected patients with ECD.

ECD is estimated to affect 600 to 700 patients worldwide. Approximately 54 percent of patients with ECD have the BRAF V600E mutations. The efficacy of Vemurafenib (Zelboraf) for the treatment of ECD was studied in 22 patients with BRAF-V600E-mutation positive ECD. The trial measured the percent of patients who experienced a complete or partial reduction in tumor size (overall response rate). In the trial, 11 patients (50 percent) experienced a partial response and 1 patient (4.5 percent) experienced a complete response.

Somewhat astonishing and troubling, at least for this author being concerned with individualized human drug safety issues, is the catalogue of the side effects of Vemurafenib (Zelboraf), some common and some most serious if not life-treathening, which have occurred in the very small number of 22 patients already. Thus, common side effects of in these patients included joint pain (arthralgia); small, raised bumps (maculo-papular rash); hair loss (alopecia); fatigue; change in the heart’s electrical activity (prolonged QT interval) and skin growths (papilloma). Severe side effects included the development of new cancers (skin cancer, squamous cell carcinoma or other cancers), growth of tumors in patients with BRAF wild-type melanoma, hypersensitivity reactions (anaphylaxis and DRESS syndrome), severe skin reactions (Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN), heart abnormalities (QT prolongation), liver damage (hepatotoxicity), photosensitivity, severe reactions in the eye (uveitis), immune reactions after receiving radiation treatment (radiation sensitization and radiation recall), kidney failure and thickening of tissue in the hands and feet (Dupuytren’s contracture and plantar fascial fibromatosis). Vemurafenib (Zelboraf) can cause harm to a developing fetus; women should be advised of the potential risk to the fetus and to use effective contraception.

While the arrival of a therapy option for patients with ECD is certainly welcome, great prudence in its application seems to be necessary, both for the therapy providers and the recipients (patients) alike.


Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.

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