de Rosa Francesco, Ridolfi Laura, Fiammenghi Laura, Petrini Massimiliano, Granato Anna M, Ancarani Valentina, Pancisi Elena, Soldati Valentina, Cassan Serena, Bulgarelli Jenny, Framarini Massimo, Tauceri Francesca, Migliori Giuseppe, Brolli Claudia, Gentili Giorgia, Petracci Elisabetta, Nanni Oriana, Riccobon Angela, Ridolfi Ruggero, Guidoboni Massimo
aImmunotherapy-Cell Therapy and Biobank bUnit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola cAdvanced Oncological Surgery dBlood Transfusion Unit, Morgagni-Pierantoni Hospital, Forlì eBlood Products Factory, Azienda USL Romagna, Cesena (FC), Italy.
Melanoma Res. 2017 Aug;27(4):351-357. doi: 10.1097/CMR.0000000000000356.
Although immunomodulating antibodies are highly effective in metastatic melanoma, their toxicity, related to the activation of T lymphocytes, can be severe. Anticancer vaccines promote a fairly specific response and are very well tolerated, but their effectiveness has yet to be demonstrated. We have been treating patients with advanced melanoma with an autologous dendritic cell vaccine since 2001; to better characterize the safety and efficacy of our product, we designed a retrospective study on all of our patients treated with the vaccine to date. We retrospectively reviewed both case report forms of patients included in clinical trials and medical records of those treated within a compassionate use program. Response was assessed according to the Response Evaluation Criteria In Solid Tumors criteria and toxicity has been graded according to CTCAE 4.0. Although the response rate has been rather low, the median overall survival of 11.4 months and the 1-year survival rate of 46.9% are encouraging, especially considering the fact that data were obtained in a heavily pretreated population and only about one quarter of the patients had received ipilimumab and/or BRAF inhibitors. Multivariate analysis confirmed that the development of an immune response was significantly correlated with a better prognosis (hazard ratio 0.54; P=0.019). The adverse events observed were generally mild and self-limiting. Our analysis confirms the excellent tolerability of our vaccine, making it a potential candidate for combination therapies. As efficacy seems largely restricted to immunoresponsive patients, future strategies should aim to increase the number of these patients.
尽管免疫调节抗体在转移性黑色素瘤中非常有效，但其与T淋巴细胞激活相关的毒性可能很严重。抗癌疫苗能引发相当特异的反应，且耐受性良好，但其有效性尚未得到证实。自2001年以来，我们一直用自体树突状细胞疫苗治疗晚期黑色素瘤患者；为了更好地描述我们产品的安全性和有效性，我们对迄今为止所有接受该疫苗治疗的患者设计了一项回顾性研究。我们回顾性审查了临床试验中纳入患者的病例报告表以及在同情用药项目中接受治疗患者的病历。根据实体瘤疗效评价标准评估反应，毒性根据CTCAE 4.0进行分级。尽管反应率相当低，但11.4个月的中位总生存期和46.9%的1年生存率令人鼓舞，尤其是考虑到数据是在经过大量预处理的人群中获得的，并且只有约四分之一的患者接受过伊匹单抗和/或BRAF抑制剂治疗。多变量分析证实，免疫反应的发生与较好的预后显著相关（风险比0.54；P = 0.019）。观察到的不良事件通常较轻且为自限性。我们的分析证实了我们疫苗具有良好的耐受性，使其成为联合治疗的潜在候选药物。由于疗效似乎在很大程度上仅限于免疫反应性患者，未来的策略应旨在增加这类患者的数量。
