Case report: Treatment of metastatic dedifferentiated chondrosarcoma with pembrolizumab yields sustained complete response

Abstract

Dedifferentiated chondrosarcomas (DDCS) are aggressive tumors with poor outcomes. Treatment of localized DDCS is primarily surgical, though most patients present with unresectable or metastatic disease. Systemic treatment options for advanced DDCS are limited, and the benefits of chemotherapy in this patient population remain controversial. Among other systemic therapy options, there is emerging clinical evidence to support the use of immunotherapy in patients with advanced DDCS. However, studies regarding the efficacy of immunotherapy in advanced DDCS are limited. Here, we present the case of a patient with metastatic, programmed death-ligand 1 (PD-L1)-positive DDCS treated with pembrolizumab who showed a sustained complete response for 24 months after initiation of therapy. To our knowledge, this case represents one of few documented cases of metastatic chondrosarcoma with sustained response to immunotherapy. The impressive response seen with PD-L1 inhibition in our patient indicates that immunotherapy is a successful treatment option in a subset of DDCS patients, and further investigation is needed to identify potential responders to immunotherapy.

A Systematic Review of Adjuvant Chemotherapy in Localized Dedifferentiated Chondrosarcoma

“…Increasing clinical evidence indicates that immunotherapy might be effective against advanced DDCS [73][74][75][76][77]. Kostine et al analyzed DDCS tissues, showing the expression of programmed cell death 1-ligand 1 (PD-L1) in 52% of samples and large T-cell infiltration [73].…”

Dedifferentiated Chondrosarcoma from Molecular Pathology to Current Treatment and Clinical Trials

“…In a case report study by Singh et al, which examined the effect of immunotherapy on PD-L1-positive DDCS, pembrolizumab (200 mg every 3 weeks) was administered after palliative resection. The patient showed a remarkable response with regression of metastatic foci and a complete sustained response for 24 months [58]. Among 22 whole-tissue samples of DDCS analysed by Kostine et.…”

“…Several studies have shown that DDCS tumours are often infiltrated by various immune cells, including macrophages and lymphocytes [7,29,[56][57][58]. Malchenko et al study of lung metastases in DDCS observed the presence of leukocyte infiltration in these metastases, which may have been involved in the metastatic spread in DDCS.…”

“…In these situations, the focus of treatment shifts towards palliative treatment. Palliative treatments for dedifferentiated chondrosarcoma may involve chemotherapy [10,18], immunotherapy [58,61,64], and targeted treatment [160,161].…”

Emerging Treatments Targeting the Tumor Microenvironment for Advanced Chondrosarcoma

“…After ten months, the patient reported the presence of an unchanged 4 mm pulmonary nodule and no metastatic disease in the abdomen and pelvis. Surprisingly, although after 29 cycles he discontinued the pembrolizumab treatment due to immunotherapy-induced psoriatic arthritis, the patient continued to have a complete response on surveillance imaging [ 122 ].…”