Sequential Imatinib and Anti-PD-1 Therapy in KIT-Altered Melanoma: Mechanistic Insights and Clinical Benefit

Patients received imatinib monotherapy as induction for six weeks, followed by combination therapy with toripalimab, an anti–PD-1 antibody. The combiniation therapy was well-tolerated and demonstrated encouraging clinical activity, with an objective response rate (ORR) of 59.4% in the overall cohort, 73.9% in patients with exon 11/13 mutations, and 100% in those with exon 11 mutation plus amplification—markedly higher than the ORRs of 23.3% with imatinib monotherapy and 25.7% with anti–PD-1 monotherapy.

Median progression-free survival and overall survival were 8.2 months (95% CI, 6.5–9.9) and 15.1 months (95% CI, 13.1–20.8), respectively. These results support the use of imatinib as an immune-sensitizing induction therapy prior to PD-1 blockade in KIT-altered melanoma and highlight the therapeutic relevance of OGT-mediated PD-L1 regulation.