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Angiosarcoma patients treated with immune checkpoint inhibitors: a case series of seven patients from a single institution.

ABSTRACT: BACKGROUND:Angiosarcoma is an uncommon endothelial malignancy and a highly aggressive soft tissue sarcoma. Due to its infiltrative nature, successful management of localized angiosarcoma is often challenging. Systemic chemotherapy is used in the metastatic setting and occasionally in patients with high-risk localized disease in neoadjuvant or adjuvant settings. However, responses tend to be short-lived and most patients succumb to metastatic disease. Novel therapies are needed for patients with angiosarcomas. METHODS:We performed a retrospective analysis of patients with locally advanced or metastatic angiosarcoma, who were treated with checkpoint inhibitors at our institution. We collected their clinical information and outcome measurements. In one patient with achieved complete response, we analyzed circulating and infiltrating T cells within peripheral blood and tumor tissue. RESULTS:We have treated seven angiosarcoma (AS) patients with checkpoint inhibitors either in the context of clinical trials or off label [Pembrolizumab + Axitinib (NCT02636725; n?=?1), AGEN1884, a CTLA-4 inhibitor (NCT02694822; n?=?2), Pembrolizumab (n?=?4)]. Five patients had cutaneous angiosarcoma, one primary breast angiosarcoma and one radiation-associated breast angiosarcoma. At 12 weeks, 5/7 patients (71%) had partial response of their lesions either on imaging and/or clinical exam and two (29%) had progressive disease. 6/7 patients are alive to date and, thus far, 3/7 patients (43%) have progressed (median 3.4?months)- one achieved partial response after pembrolizumab was switched to ongoing Nivolumab/Ipilimumab, one died of progressive disease at 31?weeks (primary breast angiosarcoma) and one was placed on pazopanib. One patient had a complete response (CR) following extended treatment with monotherapy AGEN1884. No patient experienced any ? grade 2 toxicities. CONCLUSIONS:This case series underscores the value of targeted immunotherapy in treating angiosarcoma. It also identifies genetic heterogeneity of cutaneous angiosarcomas and discusses specific genetic findings that may explain reported benefits from immunotherapy.

SUBMITTER: Florou V

PROVIDER: S-EPMC6686562 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Angiosarcoma patients treated with immune checkpoint inhibitors: a case series of seven patients from a single institution.

Florou Vaia V Rosenberg Andrew E AE Wieder Eric E Komanduri Krishna V KV Kolonias Despina D Uduman Mohamed M Castle John C JC Buell Jennifer S JS Trent Jonathan C JC Wilky Breelyn A BA

Journal for immunotherapy of cancer 20190808 1

<h4>Background</h4>Angiosarcoma is an uncommon endothelial malignancy and a highly aggressive soft tissue sarcoma. Due to its infiltrative nature, successful management of localized angiosarcoma is often challenging. Systemic chemotherapy is used in the metastatic setting and occasionally in patients with high-risk localized disease in neoadjuvant or adjuvant settings. However, responses tend to be short-lived and most patients succumb to metastatic disease. Novel therapies are needed for patien ...[more]

PMID: 31395100

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Project description:BackgroundImmune checkpoint inhibitors (ICIs) in the setting of liver transplant (LT) pose a risk of rejection and hold unclear benefit in both the neoadjuvant (pre-transplant) and post-transplant salvage setting. In the pre-transplant setting, neoadjuvant ICIs may serve as a bridge to LT by downstaging disease burden to fit within transplant criteria. Outcomes in this setting include patients who had successful transplants without complications to patients who suffered severe complications, including fatal hepatic necrosis and graft failure requiring re-transplant. Some authors suggest having a period of three months between checkpoint inhibition and transplant may help mitigate adverse effects. In the post-LT setting, there are few treatment options if there is a recurrence of disease, which forces treatment teams to reconsider checkpoint inhibitors. Again, a longer period of time between transplant and checkpoint inhibition may reduce risk of rejection. Case reports of patients treated with ICIs post-transplant utilized either nivolumab or pembrolizumab. As combination atezolizumab/bevacizumab is a relatively new treatment option for unresectable hepatocellular carcinoma (HCC), there are only three reported cases using this combination in the post-LT setting. While there were no cases of rejection, all three cases had progression of disease. As immunotherapy joins transplantation as a mainstay of treatment for HCC, it remains unclear how to best navigate when the treatment course involves both immune activation and immunosuppression.Case descriptionPatients who had an LT and were treated with ICIs (pre or post LT) at the University of Cincinnati were included in this retrospective chart review.ConclusionsFatal rejection remains a significant risk even 4 years after LT. Neoadjuvant ICIs also pose a risk for acute cellular rejection; however, this may not always be clinically significant. Graft versus host disease (GVHD) may be an additional, previously unreported risk of ICIs in the setting of LT. Prospective studies are needed to understand benefits and risks of checkpoint inhibitors in the LT setting.

Project description:Simple Summary Immune checkpoint inhibitors (ICIs) are currently widely used in many types of cancer. However, some patients could not benefit from ICIs. In addition, a standardized biomarker for predicting the efficacy of ICIs is currently unavailable. Thus, we determined whether peripheral blood immune cells could be predicting markers. In contrast with previous studies, we focused on changes in immune cell fraction and the relationship between efficacy of ICIs including response rate and survival outcomes. Results revealed significant correlations between changes in NKp46-/CD56+ NK cell fraction and treatment outcomes with ICIs. Abstract Background: With the development of immunology, immune checkpoint inhibitors (ICIs) have been widely used in various cancer treatments. Although some patients can benefit from ICIs, other patients have no response to ICIs or suffer from hyperprogression. There has been no biomarker for predicting the efficacy of ICIs. Thus, the objective of this study was to find biomarkers for predicting the efficacy of ICIs using peripheral blood. Methods: Adults patients planned to be treated with ICIs were enrolled in this study. Blood sampling was carried out before and after administration of ICIs. Changes of immune cell fraction were analyzed for each patient. Results: Among 182 patients enrolled, immune cell analysis was performed for 90 patients. The objective response rate was 14.4% (n = 13/90). The median progression-free survival (PFS) was 6.0 months (95% CI: 3.1–8.9 months), and the median overall survival (OS) was 13.9 months (95% CI: 5.6–22.2 months). Significant benefits in ORR and OS were shown for patients with increased NKp46-/CD56+ NK cells (p = 0.033 and p = 0.013, respectively). The PFS tended to be longer in these patients, although the difference was not statistically significant (p = 0.050). Conclusion: Changes of immune cell fraction before and after administration of ICIs could be a novel biomarker for predicting the efficacy of immunotherapy.

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Angiosarcoma patients treated with immune checkpoint inhibitors: a case series of seven patients from a single institution.

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Angiosarcoma patients treated with immune checkpoint inhibitors: a case series of seven patients from a single institution.

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