A Pilot Study of Anti-CTLA4 Antibody Ipilimumab in Patients with Synovial Sarcoma.
A Pilot Study of Anti-CTLA4 Antibody Ipilimumab in Patients with Synovial Sarcoma.
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作者：
Maki RG;Jungbluth AA;Gnjatic S;Schwartz GK;D'Adamo DR;Keohan ML;Wagner MJ;Scheu K;Chiu R;Ritter E;Kachel J;Lowy I;Old LJ;Ritter G
背景。复发性滑膜肉瘤患者几乎没有全身治疗的选择。由于它们表达大量内源性 CT（癌睾丸）抗原，例如 NY-ESO-1，因此我们研究了单药抗 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。采用西蒙两阶段二期设计来确定是否有足够的活动来进行进一步的研究。主要终点是 RECIST 1.0 的肿瘤缓解率。患者每 3 周静脉注射 3mg/kg 的易普利姆玛 (ipilimumab)，持续三个周期，然后重新分期。接受额外三周治疗休息的患者可以进行重新治疗。在治疗前和治疗期间收集血清和外周血单核细胞以评估 NY-ESO-1 特异性免疫。结果。 6 名患者入组并接受 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显示出疾病进展的临床或放射学证据，RECIST 缓解率为 0%。该研究因进展缓慢、缺乏活动和缺乏免疫反应而被停止。没有证据表明治疗前后对 NY-ESO-1 出现临床显着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 CT 抗原高表达，但既没有临床益处，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症生殖细胞抗原的能力可能有助于确定观察到的免疫学或临床活性缺乏的原因。
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.