Long-term complete remission with Ipilimumab in metastatic castrate-resistant prostate cancer: case report of two patients.
Long-term complete remission with Ipilimumab in metastatic castrate-resistant prostate cancer: case report of two patients.
复制标题
DOI：
10.1186/s40425-017-0232-7
复制
发表时间：
2017
影响因子：
10.9
通讯作者：
Fizazi K
中科院分区：
文献类型：
--
作者：
Cabel L;Loir E;Gravis G;Lavaud P;Massard C;Albiges L;Baciarello G;Loriot Y;Fizazi K
前列腺癌是男性最常见的癌症之一，也是全球癌症死亡率的第四大原因。尽管近年来在转移性去势抵抗性前列腺癌（mCRPC）患者方面取得了重大进展，但由于下一代雄激素受体轴靶向药物、紫杉烷类药物和骨靶向药物的出现，免疫疗法尚未得到广泛批准和用于治疗前列腺癌。两项使用 ipilimumab（一种抗 CTLA-4（细胞毒性 T 淋巴细胞抗原 4）抗体）的大型研究报告称，无进展生存期有所改善，但在初步分析中并没有统计学上改善总生存期（CA184 043 和 CA184 095）。在这里，我们报告了两名在这些试验中接受伊匹单抗治疗的患者，在开始伊匹单抗治疗后分别进行了 64 个月和 52 个月的随访，但仍处于长期完全缓解状态。对两名患者之一的存档前列腺活检样本进行 hMLH1、hMSH2、hMSH6 和 PMS2 免疫组织化学染色；他们表现出正常的蛋白质表达。有趣的是，对于该患者来说，在档案前列腺活检以及 Treg FoxP3+ T 细胞中观察到高 CD3+ 和 CD8+ T 细胞浸润。 Ipilimumab 在 CRPC 患者中产生临床活性，包括没有可检测到的残留疾病的长期缓解者。
Prostate cancer is one of the most common cancers in men and the fourth leading cause of cancer mortality worldwide. Although major progress has been achieved in the last years for patients with metastatic castrate-resistant prostate cancer (mCRPC), thanks to next-generation androgen receptor axis targeted drugs, taxanes, and bone-targeted agents, immunotherapy has not been widely approved and used for the treatment of prostate cancer. Two large studies with ipilimumab, an anti-CTLA-4 (cytotoxic T-lymphocyte antigen 4) antibody reported improved progression-free survival, but not statistically improved overall survival at the primary analysis (CA184 043 and CA184 095). Here, we report on two patients who received ipilimumab in these trials and are still in long-term complete remission with a follow-up of 64 and 52 months respectively after the initiation of ipilimumab. Immunohistochemical staining for hMLH1, hMSH2, hMSH6 and PMS2 was performed on archival prostate biopsy samples from one of the two patients; they exhibited normal protein expression. Interestingly for this patient, a high CD3+ and CD8+ T cell infiltration was observed on archival prostate biopsies as well as Treg FoxP3+ T cells. Ipilimumab produces clinical activity in patients with CRPC, including very long responders with no detectable residual disease.