Belderbos Robert A, Baas Paul, Berardi Rossana, Cornelissen Robin, Fennell Dean A, van Meerbeeck Jan P, Scherpereel Arnaud, Vroman Heleen, Aerts Joachim G J V
Department of Pulmonary Medicine, Erasmus MC Rotterdam, The Netherlands.
Erasmus MC Cancer Institute, Erasmus MC Rotterdam, The Netherlands.
Transl Lung Cancer Res. 2019 Jun;8(3):280-285. doi: 10.21037/tlcr.2019.05.05.
Malignant pleural mesothelioma (MPM) is an aggressive, treatment resistant neoplasm. The current treatment, consisting of antifolate and platinum-based chemotherapy, improves the median overall survival with only 3 months. Adjuvant bevacizumab generates an additional 2 months survival benefit. Checkpoint inhibitors (CI) have shown promising clinical effects in only a minority of patients. A possible reason is that MPM patients have low numbers of tumor-infiltrating CD8 T-cells. Dendritic cell (DC) therapy can induce an immune response and activate tumor-specific CD8 T-cells. Allogeneic mesothelioma tumor-lysate loaded DC therapy has proven effective in mice and safe and feasible in humans. We have designed a randomized, phase II/III, multicenter, open-label trial to examine the efficacy of DC therapy in humans with histologically proven MPM.
In this open-label, multicenter, randomized phase II/III trial patients will be randomized to receive either DC therapy plus best supportive care (BSC) or BSC alone according to the discretion of the local investigator after first line chemotherapy treatment. The primary end point will be overall survival. The secondary endpoints will be safety and tolerability, progression-free survival, overall response rate and quality of life.
This phase II/III trial will determine whether DC therapy in patients with MPM is safe and effective as a maintenance treatment and subsequently might be a new treatment option for MPM.
恶性胸膜间皮瘤（MPM）是一种侵袭性强、对治疗耐药的肿瘤。目前的治疗方案包括抗叶酸和铂类化疗，仅将中位总生存期提高了3个月。辅助使用贝伐单抗可使生存期额外延长2个月。检查点抑制剂（CI）仅在少数患者中显示出有前景的临床效果。一个可能的原因是MPM患者肿瘤浸润性CD8 T细胞数量较少。树突状细胞（DC）疗法可诱导免疫反应并激活肿瘤特异性CD8 T细胞。异体间皮瘤肿瘤裂解物负载的DC疗法已在小鼠中证明有效，在人类中安全可行。我们设计了一项随机、II/III期、多中心、开放标签试验，以研究DC疗法对经组织学证实为MPM的人类患者的疗效。
在这项开放标签、多中心、随机II/III期试验中，患者在一线化疗后，将根据当地研究者的判断随机接受DC疗法加最佳支持治疗（BSC）或仅接受BSC。主要终点将是总生存期。次要终点将是安全性和耐受性、无进展生存期、总缓解率和生活质量。
这项II/III期试验将确定DC疗法作为MPM患者的维持治疗是否安全有效，随后可能成为MPM的一种新的治疗选择。
