Hepatotoxicity, Including Hepatic Veno-Occlusive Disease (VOD) (aka Sinusoidal Obstruction Syndrome)

Pivekimab sunirine can cause hepatotoxicity, including VOD (aka Sinusoidal Obstruction Syndrome), a severe form of hepatotoxicity. In the CADENZA study, VOD occurred in 6% (7/116) of adult patients during treatment or following a subsequent hematopoietic stem cell transplantation (HSCT). Of the 7 total patients who developed VOD, 3 patients had treatment-naïve BPDCN and 4 patients had relapsed/refractory BPDCN. Among all 116 patients treated with pivekimab sunirine at 0.045 mg/kg, VOD occurred in 2/116 (2%) during treatment, with onset up to 30 days after the last dose. Among 19 patients with BPDCN who proceeded to HSCT, VOD occurred in 5/19 patients (26%), including two fatal cases. The median time from subsequent HSCT to onset of VOD was 11 days (range: 7 – 25 days).

After receiving pivekimab sunirine, patients should be closely monitored for signs and symptoms of VOD including elevations in ALT, AST, total bilirubin, hepatomegaly (which may be painful), rapid weight gain, and ascites. Monitor liver tests, including ALT, AST, and total bilirubin, prior to each dose of pivekimab sunirine. Based on elevations of liver tests, delay pivekimab sunirine. In patients who experience VOD, discontinue pivekimab sunirine and treat according to standard medical practice [see Dosage and Administration (2.4)].