Do patients with myxofibrosarcoma and undifferentiated pleomorphic sarcoma have different clinical outcomes to immune checkpoint blockade-based therapy?
Authors: Evan Rosenbaum, Kenneth Seier, Martina Bradic, Rhoena Desir, Ciara Marie Kelly, Sujana Movva, Viswatej Avutu, Lauren Baker Banks, Jason Earl Chan, Ping Chi, Mark Andrew Dickson, Mary Louise Keohan, Mrinal M. Gounder, Robert G. Maki, Samuel Singer, Li-Xuan Qin, Cristina R. Antonescu, William D. Tap, Sandra P. D'Angelo
Journal: Journal of Clinical Oncology (2024)

11567 Background: Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are distinct histologic subtypes of soft tissue sarcoma that exist on a spectrum of dedifferentiation. Molecular analyses have found MFS and UPS to be indistinguishable, except for a higher expression of matrix-associated genes in MFS. While immune checkpoint blockade (ICB) is a recognized treatment option for UPS patients according to the National Comprehensive Cancer Network guidelines, clinical outcomes to ICB-based therapy in MFS have not been well described. Methods: The objectives of this study were to compare the overall response rate (ORR), progression free survival (PFS), and overall survival (OS) of MFS and UPS patients treated with ICB-based therapy. We retrospectively searched our clinical trial database for MFS and UPS patients treated at our Center with ICB-based therapy. Given the low number of MFS patients identified, we included any MFS patient treated with ICB-based therapy off-label. To determine whether MFS patients treated off-label differed from those treated on a study, a sensitivity analysis was performed comparing PFS and OS between these two groups. Kaplan Meier methods were used to analyze OS and PFS and log rank test was used to compare between groups. ORR were compared using Fisher’s exact test. Results: A total of 70 patients were included, 43 (61%) with UPS and 27 (39%) with MFS. All UPS patients and 13 MFS patients were treated on one of 8 different clinical trials, two utilized ICB alone and 6 combined ICB with another agent. Eleven of 14 (79%) MFS patients treated off-label received ICB alone; 3 (21%) received ICB plus another agent. Fifty-five patients treated on trials were assessed by RECIST 1.1 (12 MFS and 43 UPS). The median age of MFS patients was higher than UPS (69.5 and 57.2, respectively). Both cohorts were predominantly male (55.6% in MFS and 60.5% in UPS) and had a median of 1 prior line of therapy (range: 0 – 6 in MFS and 0 - 7 in UPS). The median myxoid component of baseline MFS tumors was 30% (range: 10 – 90%). Median PFS and OS (in months) and ORR (%) are outlined (Table). A sensitivity analysis within MFS did not find a significant difference between MFS patients treated off or on a clinical trial. Conclusions: In this retrospective analysis, clinical outcomes to ICB-based therapy did not differ between MFS and UPS patients. Based on these data, it may be reasonable to (a) consider ICB as a treatment option for unresectable or metastatic MFS refractory to standard chemotherapy and (b) group UPS and MFS together onto a single cohort in clinical studies of ICB-based therapy. [Table: see text]