Recurrent synovial sarcoma NOS

For patients with recurrent synovial sarcoma, the survival rate after relapse is poor (30%–40% at 5 years). Factors associated with outcome after relapse include duration of first remission (> or ≤ 18 months) and lack of a second remission.[46,47]

In a German experience, surgical resection of metastatic disease was the most common way to achieve a second complete remission.[47] Maintenance chemotherapy with oral trofosfamide, idarubicin, and etoposide or oral cyclophosphamide and intravenous vinblastine was administered on an individual basis.

A consortium of six European referral centers reported a retrospective review of patients younger than 21 years with recurrent synovial sarcoma. Among 41 patients, the first relapses occurred within 3 to 132 months (median, 18 months) after first diagnoses. The relapses were local in 34% of patients, metastatic in 54%, and both in 12%. Treatments at first relapse included surgery in 56% of patients, radiation therapy in 34%, and systemic therapy in 88%. In all, 36 patients received second-line medical treatment, which included chemotherapy in 32 patients (with 10 different regimens) and targeted therapy in 4 patients. No patient was included in early-phase clinical trials as second-line therapy. The overall response rate was 42%. The median EFS was 12 months, and the postrelapse 5-year EFS rate was 15.8%. The median OS was 30 months, and the postrelapse 5-year OS rate was 22.2%. In a Cox multivariable regression analysis, OS was significantly associated with time and type of relapse.[48]

Radiation therapy (stereotactic body radiation therapy) can be used to target select pulmonary metastases. This is usually considered after a minimum of one resection to confirm metastatic disease. Radiation therapy is particularly appropriate for patients with lesions that threaten air exchange because of their location adjacent to bronchi or cause pain by invading the chest wall.[49]

Between 70% to 80% of synovial sarcomas express NY-ESO-1, an immunogenic cancer testis antigen.[50] NY-ESO-1 can be targeted with adoptive transfer of T cells engineered to express NY-ESO-1c259, an affinity-enhanced T-cell receptor (TCR) targeting NY-ESO-1/LAGE1a.[51] The procedure to produce the genetically engineered T cells restricts their reactivity to a single HLA type. All clinical trials of this technology chose HLA-A*02 as the initial target and limited eligibility to patients whose tumors expressed NY-ESO-1 and who had HLA-A*02. In a multi-institutional trial, confirmed antitumor responses occurred in 50% of patients (6 of 12) and were characterized by tumor shrinkage over several months. Circulating NY-ESO-1c259 T cells were present postinfusion in all patients, and the cells persisted for at least 6 months in all responders.[52]

An open-label, international, phase II study enrolled patients with previously treated metastatic or unresectable synovial sarcoma and myxoid round cell liposarcoma.[53] Fifty-two patients with HLA-A*02 and tumors that expressed melanoma-associated antigen A4 (MAGE-A4) received a single intravenous dose of afamitresgene autoleucel (afami-cel) after lymphodepletion. Afami-cel is a MAGE-A4–directed, genetically modified, autologous T-cell immunotherapy. The overall response rate (the primary end point of the study) was 37% (19 of 52; 95% CI, 24%–51%), 39% (17 of 44; 95% CI, 24%–55%) for patients with synovial sarcoma, and 25% (2 of 8; 95% CI, 3%–65%) for patients with myxoid round cell liposarcoma. Cytokine release syndrome and cytopenias were the most frequent side effects. The authors concluded that afami-cel treatment resulted in durable responses in heavily pretreated eligible patients with synovial sarcoma.[53] These data led to FDA approval of afami-cel in adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A*02 positive, and whose tumors express the MAGE-A4 antigen.