1. A randomized, non-comparative phase 2 study of neoadjuvant immune-checkpoint blockade in retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma.
- Author
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Roland CL, Nassif Haddad EF, Keung EZ, Wang WL, Lazar AJ, Lin H, Chelvanambi M, Parra ER, Wani K, Guadagnolo BA, Bishop AJ, Burton EM, Hunt KK, Torres KE, Feig BW, Scally CP, Lewis VO, Bird JE, Ratan R, Araujo D, Zarzour MA, Patel S, Benjamin R, Conley AP, Livingston JA, Ravi V, Tawbi HA, Lin PP, Moon BS, Satcher RL, Mujtaba B, Witt RG, Traweek RS, Cope B, Lazcano R, Wu CC, Zhou X, Mohammad MM, Chu RA, Zhang J, Damania A, Sahasrabhojane P, Tate T, Callahan K, Nguyen S, Ingram D, Morey R, Crosby S, Mathew G, Duncan S, Lima CF, Blay JY, Fridman WH, Shaw K, Wistuba I, Futreal A, Ajami N, Wargo JA, and Somaiah N
- Subjects
- Humans, Male, Female, Middle Aged, Aged, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory drug effects, Adult, Sarcoma therapy, Sarcoma immunology, Sarcoma drug therapy, Nivolumab therapeutic use, B-Lymphocytes immunology, B-Lymphocytes drug effects, Liposarcoma drug therapy, Liposarcoma immunology, Neoadjuvant Therapy methods, Retroperitoneal Neoplasms drug therapy, Retroperitoneal Neoplasms immunology, Immune Checkpoint Inhibitors therapeutic use
- Abstract
Based on the demonstrated clinical activity of immune-checkpoint blockade (ICB) in advanced dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS), we conducted a randomized, non-comparative phase 2 trial ( NCT03307616 ) of neoadjuvant nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n = 17) and extremity/truncal UPS (+ concurrent nivolumab/radiation therapy; n = 10). The primary end point of pathologic response (percent hyalinization) was a median of 8.8% in DDLPS and 89% in UPS. Secondary end points were the changes in immune infiltrate, radiographic response, 12- and 24-month relapse-free survival and overall survival. Lower densities of regulatory T cells before treatment were associated with a major pathologic response (hyalinization > 30%). Tumor infiltration by B cells was increased following neoadjuvant treatment and was associated with overall survival in DDLPS. B cell infiltration was associated with higher densities of regulatory T cells before treatment, which was lost upon ICB treatment. Our data demonstrate that neoadjuvant ICB is associated with complex immune changes within the tumor microenvironment in DDLPS and UPS and that neoadjuvant ICB with concurrent radiotherapy has significant efficacy in UPS., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2024
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