Tumor lysis syndrome induced by BRAF/MEK double blockade in a patient with metastatic melanoma: A first case report

Abstract

Dear Editor, Tumor lysis syndrome (TLS) is a rare oncologic complication arising during malignant tumor treatment. It occurs when numerous malignant cells are destroyed within 12– 72 h after treatment initiation in aggressive leukemia or malignant lymphoma patients but rarely occurs in melanoma patients.1 We report a case of TLS induction by BRAF/MEK double blockade in a 51yearold Japanese woman with severe pleural metastases from cutaneous melanoma. A 51yearold woman visited our hospital due to massive left pleural effusion (Figure 1a). She underwent surgery for primary cutaneous melanoma (superficial spreading melanoma) of the right chest in 2007 and was diagnosed with pT2bN0M0, stage IIb cancer (American Joint Committee on Cancer, 7th edition). Computed tomography (CT) showed a thickwalled left pleural cavity with nodules (Figure 1b,c). Positron emission tomography/ CT showed abnormal uptake at nodular sites in the left pleura (Figure 1d). Pleural biopsy confirmed the diagnosis as pleural metastasis of BRAFV600Emutated melanoma. She received BRAF/MEK inhibitors, encorafenib (450 mg/day) and binimetinib (90 mg/day) (day 1). Despite discontinuing BRAF/MEK inhibitors within 24 h because of bilateral central serous retinal detachment (SRD) (day 2), TLS was diagnosed 2 days later (day 3) based on hyperkalemia (6.1 mmol/L potassium), hyperuricemia (12.4 mg/dL uric acid), and acute renal failure (3.12 IU/L creatinine) (Figure 1e). TLS was successfully treated with hydrating agents, diuretics, and uric acid (synthesis) inhibitors, and SRD improved shortly afterward only by discontinuing BRAF/MEK inhibitors. One week postonset, she was retreated with reduced doses of encorafenib (200 mg/day) and binimetinib (30 mg/day). Three weeks after that, her pleural effusion was cleared without TLS recurrence (Figure 1f, g). Tumor lysis syndrome is a lifethreatening complication, and typical symptoms include hyperkalemia, hyperphosphatemia, and hyperuricemia, which cause acute renal failure and fatal arrhythmia.1 Administrating i.v. hydration and hypouricemic agents before initiation of treatment helps prevent TLS.2 Melanoma was not sensitive to chemotherapy until BRAF/MEK inhibitors and immune checkpoint inhibitors (ICI) were included; these are more effective than the previous standard treatment agent, dacarbazine. BRAF/MEK inhibitors are especially characterized by eliciting a rapid response. Recently, several melanoma TLS cases due to BRAF/MEK inhibitor and ICI treatment have been reported.3,4 In the present case, TLS occurred probably due to the following reasons. First, the tumor was bulky. The left pleura was completely covered with metastatic tumor cells. The higher the tumor volume, the higher the TLS risk. Second, the left pleural cavity was filled with pleural fluid. Pleural effusion is considered a risk factor for TLS in some diseases.5 Third, encorafenib and binimetinib combination therapy yielded rapid response and high effectiveness. Numerous malignant cells were destroyed at once. In conclusion, BRAF/MEK inhibitor combination therapy is highly effective for treating BRAF mutant melanoma, providing a rapid response; however, due to their effectiveness, to avoid TLS, they should be cautiously used, especially in cases with large tumor burden and/or massive pleural effusion associated with metastasis before BRAF/MEK inhibitor treatment.