Case Report: Response to Regional Melphalan via Limb Infusion and Systemic PD1 Blockade in Recurrent Myxofibrosarcoma: A Report of 2 Cases

Abstract

Treatment options for patients with advanced sarcoma remain limited. Promising responses to checkpoint inhibition have been observed, but responses to single-agent PD-1 inhibition are rare. We report on two patients with multiply recurrent myxofibrosarcoma treated with the combination of regionally administered melphalan (via isolated limb infusion) and pembrolizumab. Both patients had recurrent disease after multiple surgical resections and radiation. Analysis of primary tumors demonstrated microsatellite stable tumors with few mutations. After combination treatment, one patient had a significant partial response of 6 months duration, the second patient had a complete response of 2 years duration. Post treatment biopsies demonstrated immune infiltration into the tumor. These promising responses in patients with multiply recurrent myxofibrosarcoma have prompted the development of an investigator-initiated clinical trial to formally study the combination of regional melphalan and pembrolizumab in a systematic fashion (NCT04332874).

Keywords: Immunotherapy; Sarcoma; isolated limb infusion; myxofibrosarcoma; undifferentiated pleomorphic sarcoma (UPS).

Conflict of interest statement

CK reports receiving research funding from Merck, Amgen, and Agios; SD’A reports research funding from Amgen, EMD Serono, Incyte, Merck & Co., Nektar, Bristol-Myers Squibb, and Deciphera; consultancy for Amgen, EMD Serono, GlaxoSmithKline, Immune Design, Incyte, Merck & Co., Nektar, and Immunocore; reimbursement for travel expenses from EMD Serono, Merck & Co., Adaptimmune, and Immunocore. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Bartlett, D’Angelo, Kelly, Siegelbaum, Fisher, Antonescu and Ariyan.

Figures

Figure 1

Response in Case 1 treated with ILI and pembrolizumab. (A), Baseline clinical pictures of the numerous recurrent lesions. (B), 6-month follow-up demonstrating significant partial response in the infused limb. (C), CD3+ T cell infiltrate in leg soft-tissue biopsy of a responding lesion. (D), CD8+ T cell infiltrate. Immunohistochemistry images are presented at 20x magnification.

Figure 2

Response in Case 2 treated with ILI and pembrolizumab. (A), Baseline CT scan with lesions noted. (B), 2-year follow-up scan demonstrating ongoing response both in infused limb and at distant site.

Figure 3

Pathologic and immunohistochemical assessment of response. (A), Excision specimen of recurrent tumor one year prior to ILI. (B), Tibial biopsy one month after ILI showing no viable tumor. (C), Absence of PD-L1 expression post-ILI and PD-1 inhibition. (D), Brisk CD4+ T cell infiltration in tibial biopsy one month after ILI. (E), Brisk CD8+ T cell infiltration in tibial biopsy one month after ILI. (F), Brisk CD163+ macrophage infiltration in tibial biopsy one month after ILI. Images are presented at 20x magnification.