Maki Robert G, Jungbluth Achim A, Gnjatic Sacha, Schwartz Gary K, D'Adamo David R, Keohan Mary Louise, Wagner Michael J, Scheu Kelly, Chiu Rita, Ritter Erika, Kachel Jennifer, Lowy Israel, Old Lloyd J, Ritter Gerd
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA ; Departments of Medicine, Pediatrics, and Orthopaedics, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, P.O. Box 1208, New York, NY 10029-6574, USA.
Sarcoma. 2013;2013:168145. doi: 10.1155/2013/168145. Epub 2013 Feb 27.
Background. Patients with recurrent synovial sarcomas have few options for systemic therapy. Since they express large amounts of endogenous CT (cancer testis) antigens such as NY-ESO-1, we investigated the clinical activity of single agent anti-CTLA4 antibody ipilimumab in patients with advanced or metastatic synovial sarcoma. Methods. A Simon two-stage phase II design was used to determine if there was sufficient activity to pursue further. The primary endpoint was tumor response rate by RECIST 1.0. Patients were treated with ipilimumab 3 mg/kg intravenously every 3 weeks for three cycles and then restaged. Retreatment was possible for patients receiving an extra three-week break from therapy. Sera and peripheral blood mononuclear cells were collected before and during therapy to assess NY-ESO-1-specific immunity. Results. Six patients were enrolled and received 1-3 cycles of ipilimumab. All patients showed clinical or radiological evidence of disease progression after no more than three cycles of therapy, for a RECIST response rate of 0%. The study was stopped for slow accrual, lack of activity, and lack of immune response. There was no evidence of clinically significant either serologic or delayed type hypersensitivity responses to NY-ESO-1 before or after therapy. Conclusion. Despite high expression of CT antigens by synovial sarcomas of patients treated in this study, there was neither clinical benefit nor evidence of anti-CT antigen serological responses. Assessment of the ability of synovial sarcoma cell lines to present cancer-germ cell antigens may be useful in determining the reason for the observed lack of immunological or clinical activity.
背景。复发性滑膜肉瘤患者的全身治疗选择有限。由于他们表达大量内源性肿瘤睾丸（CT）抗原，如NY-ESO-1，我们研究了单药抗CTLA4抗体伊匹单抗在晚期或转移性滑膜肉瘤患者中的临床活性。方法。采用西蒙两阶段II期设计来确定是否有足够的活性以进行进一步研究。主要终点是根据RECIST 1.0标准的肿瘤反应率。患者接受伊匹单抗3mg/kg静脉注射，每3周一次，共三个周期，然后重新分期。接受额外三周治疗中断的患者可以再次治疗。在治疗前和治疗期间收集血清和外周血单个核细胞，以评估NY-ESO-1特异性免疫。结果。6名患者入组并接受了1 - 3个周期的伊匹单抗治疗。所有患者在不超过三个周期的治疗后均出现疾病进展的临床或影像学证据，RECIST反应率为0%。该研究因入组缓慢、缺乏活性和缺乏免疫反应而停止。治疗前后均没有证据表明对NY-ESO-1有临床上显著的血清学或迟发型超敏反应。结论。尽管本研究中治疗的患者滑膜肉瘤中CT抗原高表达，但既没有临床获益，也没有抗CT抗原血清学反应的证据。评估滑膜肉瘤细胞系呈递癌胚细胞抗原的能力可能有助于确定观察到的免疫或临床活性缺乏的原因。
