FDA Approves Melphalan Injection via Hepatic Delivery System as a Liver-Directed Treatment for Uveal Melanoma

On August 14, 2023, the US Food and Drug Administration (FDA) granted approval to melphalan via hepatic delivery system as a liver-directed treatment for patients with uveal melanoma with unresectable hepatic metastasis affecting <50% of the liver and no extrahepatic disease, or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation. 

This approval was based on efficacy findings from the single-arm, multicenter, open-label, FOCUS study. In this trial, 91 patients with uveal melanoma with unresectable hepatic metastases were enrolled. Patients with extrahepatic disease limited to the bone, subcutaneous sites, lymph nodes, or lung were permitted if the life-threatening component of uveal melanoma was in the liver, and extrahepatic disease was amenable to resection or radiation. Key exclusion criteria included metastases in ≥50% of the liver parenchyma, Child-Pugh Class B or C cirrhosis, or hepatitis B or C infection. 

Melphalan was administered in doses of 3 mg/kg based on body weight with a single administration maximum dose of 220 mg. Treatment was delivered via hepatic delivery system infusion into the hepatic artery every 6 to 8 weeks for up to 6 total infusions. Main efficacy outcome measures included objective response rate (ORR) and duration of response (DOR), as assessed by independent central review. 

The ORR was 36.3% and the median DOR was 14 months. The most common adverse events or laboratory abnormalities, occurring in ≥20% of patients, included thrombocytopenia, fatigue, anemia, nausea, musculoskeletal pain, leukopenia, abdominal pain, neutropenia, vomiting, increased alanine aminotransferase, prolonged activated partial thromboplastin time, increased aspartate aminotransferase, increased blood alkaline phosphatase, and dyspnea. 

Due to risk of severe peri-procedural complications including hemorrhage, hepatocellular injury, and thromboembolic events, and risk of myelosuppression resulting in severe infection, bleeding, or symptomatic anemia, melphalan is prescribed with a Black Box Warning. Because of severe peri-procedural complications, melphalan is only available through a restricted program under a Risk Evaluation and Mitigation Strategy.  

Source:

FDA approves melphalan as a liver-directed treatment for uveal melanoma. US Food and Drug Administration. August 14, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-melphalan-liver-directed-treatment-uveal-melanoma