Pembrolizumab Achieved pCR in Patient With Recurrent DDLPS

A new case report suggests that a high tumor mutational burden (TMB) and high tumor-associated macrophages (TAM) density in the tumor microenvironment (TME) may be predictors of a positive response to immune checkpoint inhibitors (ICIs) among people with dedifferentiated liposarcoma (DDLPS).

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The report is based on the experience of a patient with recurrent retroperitoneal DDLPS and is believed to be the first reported case in which such a patient achieved a pathological complete response (pCR) to pembrolizumab (Keytruda). The study was published in the World Journal of Surgical Oncology.1

Corresponding author Shun Abe, MD, PhD, of Japan’s Niigata University Graduate School of Medical and Dental Sciences, and colleagues, said tumors are typically large by the time patients with retroperitoneal DDLPS are diagnosed. As a result, complete resection of the tumor and adjacent organs and structures is the primary potentially curative treatment for such patients.

“However, the rate of recurrence remains high, occurring in up to 83.2% of these patients,” they wrote.2 “As with locally advanced or metastatic soft tissue sarcoma (STS), recurrent retroperitoneal DDLPS generally has poor prognosis with limited treatment options.”

Recent evidence has suggested that some patients with DDLPS might respond to ICI therapy, though the available evidence shows no association between TMB status and therapeutic response, Abe and colleagues said. Other evidence suggests that the tumor microenvironment (TME) might be linked with response to ICIs, they added.3

The patient at the center of the new case report was 73 years old and receiving hormone therapy for prostate cancer with lung and bone metastases at the time of his DDLPS diagnosis. Follow-up imaging related to his prostate cancer revealed a multilobulated retroperitoneal tumor in the right iliac fossa. The patient underwent macroscopically complete removal of the tumor. After 8 months, though, he was diagnosed with recurrence with peritoneal dissemination.

The patient was treated with doxorubicin, pazopanib, and eribulin, but his disseminated lesions continued to grow through each course of therapy. Genomic profiling showed that the primary tumor had a high TMB of 13 mutations/megabase, leading his clinicians to prescribe pembrolizumab at a dose of 400 mg every 6 weeks. The therapy achieved a partial response with a 56.7% decrease in target lesions, Abe and colleagues said. However, the patient developed grade 3 ICI-induced inflammatory arthritis, prompting discontinuation of pembrolizumab. He then underwent a second radical surgery, in which 9 disseminated lesions were removed. A histological examination subsequently showed he had achieved a pCR with extensive hyalinization and necrosis and no residual viable tumor cells.

Fifteen months following the second surgery, the patient was alive and disease-free, the authors said.

“This case highlights the potential efficacy of ICIs in a subset of DDLPS patients and provides valuable insights into potential predictive biomarkers for the response to ICIs in this malignancy,” Abe and colleagues said.

They noted that STS is generally considered to be “immune cold,” with low TMB. Though estimates vary somewhat, fewer than 1 in 10 patients with STS are believed to have a high TMB (defined as 10 or more mutations/megabase), they noted. The scarcity of such cases makes it difficult to know whether an increased TMB can be linked with ICI response in patients with DDLPS, but the authors said this case suggests such a correlation might exist.

Abe and colleagues said an important limitation of their study is that the TME was not analyzed until after pembrolizumab monotherapy, which may affect interpretation of the results. They noted that it is possible the use of doxorubicin helped prime the TME to response to ICI therapy.4

Overall, the investigators said their case suggests more work is needed to see which patients with DDLPS might benefit from ICIs.

“Our findings underscore the need to refine the predictive biomarkers for the response to ICIs in this malignancy in future studies,” they concluded.

References:

1. Abe S, Zhou Q, Ariizumi T, et al. Pathological complete response to pembrolizumab in recurrent retroperitoneal dedifferentiated liposarcoma with high tumor mutational burden: a case report. World J Surg Oncol. 2025;23(1):449. doi:10.1186/s12957-025-04096-3
2. Keung EZ, Hornick JL, Bertagnolli MM, Baldini EH, Raut CP. Predictors of outcomes in patients with primary retroperitoneal dedifferentiated liposarcoma undergoing surgery. J Am Coll Surg. 2014;218(2):206-217. doi:10.1016/j.jamcollsurg.2013.10.009
3. Zhu MMT, Shenasa E, Nielsen TO. Sarcomas: Immune biomarker expression and checkpoint inhibitor trials. Cancer Treat Rev. 2020;91:102115. doi:10.1016/j.ctrv.2020.102115
4. Emens LA, Middleton G. The interplay of immunotherapy and chemotherapy: harnessing potential synergies. Cancer Immunol Res. 2015;3(5):436-443. doi:10.1158/2326-6066.CIR-15-0064