Journal Article

A randomized, non-comparative phase 2 study of neoadjuvant immune-checkpoint blockade in retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma

Cope, Brandon, Ingram, Davis, Hunt, Kelly K., Duncan, Sheila, Zarzour, M. Alexandra, Lin, Patrick P., Fridman, Wolf Herman, Bishop, Andrew J., Ravi, Vinod, Lima, Cibelle F., Burton, Elizabeth M., Wu, Chia-Chin, Sahasrabhojane, Pranoti, Keung, Emily Z., Satcher, Robert L., Wistuba, Ignacio, Wargo, Jennifer A., Somaiah, Neeta, Callahan, Kate, Conley, Anthony P., Livingston, J. Andrew, Wang, Wei-Lien, Witt, Russell G., Chelvanambi, Manoj, Ratan, Ravin, Bird, Justin E., Nguyen, Sa, Traweek, Raymond S., Mathew, Grace, Araujo, Dejka, Mujtaba, Bilal, Chu, Randy A., Torres, Keila E., Feig, Barry W., Shaw, Kenna, Lazar, Alexander J., Patel, Shreyaskumar, Morey, Rohini, Guadagnolo, B. Ashleigh, Lazcano, Rossana, Ajami, Nadim, Blay, Jean-Yves, Nassif Haddad, Elise F., Parra, Edwin R., Lewis, Valerae O., Crosby, Shadarra, Mohammad, Mohammad M., Zhou, Xiao, Wani, Khalida, Futreal, Andrew, Benjamin, Robert, Lin, Heather, Zhang, Jianhua, Tawbi, Hussein A., Moon, Bryan S., Roland, Christina L., Tate, Taylor, Scally, Christopher P., Damania, Ashish

2024

Overview

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.

• Publisher: Nature Publishing Group
• Subject: Adult / Aged / B-Lymphocytes - drug effects / B-Lymphocytes - immunology / Female / Humans / Immune Checkpoint Inhibitors - therapeutic use / Immunotherapy / Liposarcoma - drug therapy / Liposarcoma - immunology / Male / Middle Aged / Neoadjuvant Therapy - methods / Nivolumab - therapeutic use / Patients / Retroperitoneal Neoplasms - drug therapy / Retroperitoneal Neoplasms - immunology / Sarcoma / Sarcoma - drug therapy / Sarcoma - immunology / Sarcoma - therapy / Surgery / T-Lymphocytes, Regulatory - drug effects / T-Lymphocytes, Regulatory - immunology / Toxicity