PDCD1 and melanoma: In melanoma, combinations of dabrafenib, trametinib, and anti-PD-1 have led to higher rates of grade 3/4 adverse events than would be expected for targeted therapy alone.177,178 Hepatotoxicity, in particular, has emerged as an important consideration across numerous studies combining immunotherapy with molecularly targeted therapy, either concomitantly or sequentially.173,184,185