Rapid and Complete Response to Combination Anti-CTLA-4 and Anti-PD-1 Checkpoint Inhibitor Therapy in a Patient With Stage IV Refractory End-stage Epithelioid Sarcoma: A Case Report

Abstract

Epithelioid sarcoma, in the relapse-refractory setting, has limited expected survival. SMARCB1 inactivation, common in epithelioid sarcoma, causes loss of INI1 protein expression and overexpression of the cancer cell growth promoting methyltransferase enzyme, EZH2. We treated a 19-year-old male with stage IV SMARCB1 inactivated epithelioid sarcoma presenting with recurrent end stage (Eastern Cooperative Oncology Group Performance Status 4) rapidly progressing bulky disease with combination ipilimumab and nivolumab. He failed standard therapy and an EZH2 inhibitor (tazemetostat). He presented (May 13, 2019) with a large (16.1×18.6 cm) soft tissue back mass extending from T10 to L3. Complete clinical regression of the back mass occurred within 2 weeks (May 28, 2019) of cycle 1 of combined checkpoint inhibition therapy followed by a positron emission tomography–negative complete remission (October 11, 2019). After a second negative positron emission tomography/computed tomography scan (January 13, 2020), checkpoint inhibition therapy was discontinued. He has returned to normal activities with a normal physical examination and Eastern Cooperative Oncology Group Performance Status of 0 at his last visit (June 29, 2020). In conclusion, combined checkpoint inhibition therapy warrants further study in the salvage setting in patients with epithelioid and other INI1 protein–deficient sarcomas seemingly regardless of prior therapy, extent of disease, and performance status.

Mediastinal Low-Grade Fibromyxoid Sarcoma With FUS-CREB3L2 Gene Fusion

“…Interestingly, two recent case reports including a 71-year-old male and a 30-year-old female, both with EWSR1-CREB3L1 fusion gene-positive refractory SEF, achieved complete response after treatment of nivolumab and ipilimumab [17]. In addition, another case report of a 19-year-old male with rapidly progressing stage IV epithelioid sarcoma who failed both doxorubicin and EZH2 inhibitor therapy obtained a durable response by combined immune checkpoint inhibitors [18]. Recently, Arbajian et al studied a series of 13 SEFs and six hybrid SEF/LGFMS cases with an expression of FUS-CREB3L2 and EWSR1-CREB3L1 fusion genes in a fibroblast cell line.…”

Proximal-type epithelioid sarcoma in pubic region expressing L-type amino acid transporter 1: A case report

“… 26 Also, a case of ES, which did not respond to conventional chemotherapy and an EZH2 inhibitor, responded completely to a combination of immune checkpoint inhibitors. 27 The development of new treatment methods for ES is currently progressing rapidly; therefore, further study on relevant treatment strategies is warranted.…”

Toward a Personalized Therapy in Soft-Tissue Sarcomas: State of the Art and Future Directions

“…Advancements of these results will derive from a phase Ib/III trial of tazemetostat in combination with doxorubicin as frontline therapy (NCT04204941) ( Table 3 ) [ 39 ]. A case report of response at the progression of tazemetostat was reported with ipilimumab and nivolumab [ 114 ]. A phase II study with this combination (NCT04416568) is currently recruiting INI1-negative tumors and among them ES ( Table 3 ) [ 39 ].…”