Long-Term Remission with Ipilimumab/Nivolumab in Two Patients with Different Soft Tissue Sarcoma Subtypes and No PD-L1 Expression

Abstract

Checkpoint inhibitor therapy has been shown to improve outcomes in multiple solid malignancies; however, data are limited in soft tissue sarcoma. We present two cases of patients with advanced soft tissue sarcoma of different subtypes (dedifferentiated liposarcoma and myxofibrosarcoma) with zero percent PD-L1 expression by immunohistochemistry who were treated with ipilimumab and nivolumab followed by maintenance nivolumab. Both patients had failed multiple lines of systemic treatment and experienced long-term remission after starting ipilimumab and nivolumab. Genetic testing revealed that no genetic mutations were found in common between the two cases. One patient received concurrent cryoablation, which may have sensitized his tumor to immunotherapy. Checkpoint inhibitor therapy may improve outcomes in soft tissue sarcoma regardless of PD-L1 status, especially when combined with cryoablation. Studies are needed to evaluate whether treatment response varies by sarcoma subtype and what molecular markers can be used to guide patient selection.

Current Landscape of Immunotherapy for Advanced Sarcoma

“…Grade 3–4 toxicity was higher in the combined treatment (14 vs. 7%). Zhou et al [ 141 ] reported two cases of PDL1-negative STS (DDLPS and myxofibrosarcoma) with long-term responses to ipilimumab plus nivolumab.…”

Soft Tissue Leiomyosarcoma With Microsatellite Instability, High Tumor Mutational Burden, and Programmed Death Ligand-1 Expression Showing Pathologic Complete Response to Pembrolizumab: A Case Report

“…However, response to ICIs has been reported to occur even in the absence of PD-L1 expression. [22][23][24][25] In addition, an angiosarcoma with a low TMB showing complete response to an ICI has also been reported, suggesting that TMB is also not entirely reliable in predicting response to immunotherapy. 26 In a study by Lam et al, 15 the authors found that the level of PD-L1 expression also correlated with the degree of T-lymphocyte infiltration in the tumor, an observation echoed by other studies.…”

Cervical Liposarcoma Revisited: A Case Report and Scoping Literature Review

“…Recent clinical studies have confirmed the benefits of the CDK4 inhibitor abemaciclib and the nuclear export inhibitor selinexor, and support the continued development of anti-MDM2 therapies [ 9 ]. Investigation of synergistic combinations of novel agents such as the checkpoint inhibitors pembrolizumab and nivolumab and other therapeutic agents is ongoing for the management of liposarcoma [ 13 , 14 ].…”