Real‐World Toxicity Experience with BRAF/MEK Inhibitors in Patients with Erdheim‐Chester Disease

Abstract Background Erdheim‐Chester disease (ECD) is a rare non‐Langerhans cell histiocytosis. The BRAF inhibitor vemurafenib is approved by the U.S. Food and Drug Administration (FDA) for patients with ECD harboring a BRAF V600E mutation. Successful treatment has also been reported with MEK‐targeted therapies, likely because of the fact that BRAF mutant–negative patients harbor MEK pathway alterations. In our Rare Tumor Clinic, we noted that these patients have frequent drug‐related toxicity, consistent with previous reports indicating the need to markedly lower doses of interferon‐alpha when that agent is used in these patients. Patients and Methods We performed a review of ten patients with ECD seen at the Rare Tumor Clinic at University of California San Diego receiving 16 regimens of targeted BRAF, MEK, or combined therapies. Results The median age of the ten patients with ECD was 53 years (range, 29–77); seven were men. The median dose percentage (percent of FDA‐approved dose) tolerated was 25% (range, 25%–50%). The most common clinically significant adverse effects resulting in dose adjustments of targeted therapies were rash, arthralgias, and uveitis. Renal toxicity and congestive heart failure were seen in one patient each. In spite of these issues, eight of ten patients (80%) achieved a partial remission on therapy. Discussion Patients with ECD appear to require substantially reduced doses of BRAF and MEK inhibitors but are responsive to these lower doses.