Multicenter phase 1b study of the combination of doxorubicin, dacarbazine, and nivolumab as upfront treatment for advanced leiomyosarcoma

Doxorubicine is capable of inducing an adaptive immune response via immunogenic cell death (ICD). A multicenter phase 1b study in Spain evaluated the combination of doxorubicin, dacarbazine, and nivolumab as upfront treatment for advanced leiomyosarcoma (aLMS). The toxicity was mild, with no grade 5 toxicity, and grade 4 neutropenia in 16.7% of patients and grade 4 thrombocytopenia in 8.3%. The combination resulted in partial response in 56.5% of patients and stable disease in 39.1%. The 6-months progression-free survival rate was 80% (95% CI 63-98). Increases of HMGB1 in blood correlated with longer PFS. The authors conclude that this scheme was feasible and had promising clinical activity among aLMS patients. The prognostic impact of HMGB1 supports the relevance of ICD activation.