Immunotherapy in sarcoma: combinations or single agents? In whom?

Abstract

First clinical trials investigating immune check point (ICP) inhibitors in patients with sarcoma, regardless histological or molecular subtypes did not demonstrate any prolonged benefit. To maximize the chance of benefit from immunotherapy, recent strategies explore the combination of treatments and aim to improve identification of responsive histological subtypes. Combination of several ICP inhibitors tends to increase toxicity and efficacy. Mechanisms of synergistic action remain unclear. Combination of ICP blockade with tyrosine kinase inhibitor increases efficacy in specific histological subtypes already identified as sensitive to each drug separately. The role of the combination is not established yet. Several ongoing trials assess the combination of ICP blockade with chemotherapy or radiotherapy. ICP blockade seems highly effective in some selected histological subtypes like alveolar soft part sarcoma, chordoma, malignant rhabdoid tumor, and angiosarcoma. Encouraging preliminary results need to be confirmed in larger cohorts and biological mechanisms that sustain this efficacy should be further explored. Adoptive cell therapy seems very promising in synovialosarcoma. Significant efforts are underway to efficiently develop immunotherapy in patients with sarcoma and better characterize patients who would benefit the most from it.