Discipline of Surgery, University of Adelaide, Adelaide Melanoma Unit, Royal Adelaide Hospital, Adelaide, South Australia Australia.
Kolling Institute University of Sydney, New South Wales, Australia.
J Immunother Cancer. 2014 Apr 15;2:9. doi: 10.1186/2051-1426-2-9. eCollection 2014.
Repetitive long-term Vaccinia Melanoma Cell Lysate (VMCL) vaccination schedules have proved clinically effective in producing Complete Responses and strong durable survivals for up to 6.1 years in a previous study of patients with advanced Stage IV and Stage IIIc melanoma. These studies were expanded to include 54 patients for further evaluation of these findings.
54 patients comprising 48 Stage IV (6 M1a, 14 M1b, 28 M1c) and 6 advanced Stage III (5 IIIc; 1 IIIb) were studied using repeated intra-dermal VMCL vaccine therapy. If disease progressed, vaccine was continued together with standard chemotherapy (DTIC and/or Fotemustine). Overall survival was the primary end-point assessed, with clinical responses and toxicity recorded.
From vaccine commencement, median overall survival was 14 months, ranging from 4 to 121 months. Kaplan-Meier survival analysis demonstrated overall 1, 2 and 3-year survival estimates of 57%, 26% and 18.5% respectively, and overall 5-year survival of 15.4%. No appreciable toxicity was observed. Complete Responses (CR) occurred in 16.7% (9) and partial responses (PR) in 14.8% (8) of patients. Stable disease was noted in a further 25 patients (46.3%). No response to therapy was apparent in 12 patients (22.2%). The overall response rate was 31.5% (CR + PR), with clinically significant responses (CR + PR + SD) in 77.8% of patients. Strong, durable clinical responses with overall survivals ≥ 23 months occurred in 29.6% of patients treated with repeated VMCL vaccine for advanced melanoma, (+/- concurrent chemotherapy).
Prolonged, repetitive VMCL vaccination immunotherapy appears to be a clinically effective means of generating relatively high CR rates, useful clinical responses and long-term survivals, with little toxicity, but remains notably under-explored. Successive immunomodulation might explain the results. Closer analysis of repetitive dosing is required to improve clinical response rates and survival, perhaps by optimising the timing of immunotherapy delivery.
Australian and New Zealand Clinical Trials Registry ANZCTRN12605000425695.
在一项针对晚期 IV 期和 IIIc 期黑色素瘤患者的研究中，重复的长期牛痘黑色素细胞瘤裂解物（VMCL）疫苗接种方案已被证明在产生完全缓解和长达 6.1 年的强烈持久生存方面具有临床疗效。这些研究扩展到包括 54 名患者，以进一步评估这些发现。
48 名 IV 期（6 名 M1a、14 名 M1b、28 名 M1c）和 6 名晚期 III 期（5 名 IIIc；1 名 IIIb）患者使用重复皮内 VMCL 疫苗治疗进行研究。如果疾病进展，疫苗将与标准化疗（DTIC 和/或 Fotemustine）一起继续使用。主要终点为总生存期，记录临床反应和毒性。
从疫苗开始，中位总生存期为 14 个月，范围为 4 至 121 个月。Kaplan-Meier 生存分析显示，1、2 和 3 年的总生存率分别为 57%、26%和 18.5%，总 5 年生存率为 15.4%。未观察到明显的毒性。16.7%（9 名）的患者出现完全缓解（CR），14.8%（8 名）的患者出现部分缓解（PR）。另有 25 名患者（46.3%）疾病稳定。12 名患者（22.2%）对治疗无反应。总有效率为 31.5%（CR+PR），77.8%的患者出现有临床意义的反应（CR+PR+SD）。29.6%的晚期黑色素瘤患者（+/-同时接受化疗）接受重复 VMCL 疫苗治疗后出现较强、持久的临床缓解，总生存期≥23 个月。
长期、重复的 VMCL 疫苗免疫治疗似乎是一种有效的临床方法，可产生相对较高的 CR 率、有用的临床反应和长期生存，毒性较小，但仍明显未被充分探索。连续免疫调节可能解释了这些结果。需要更密切地分析重复给药以提高临床反应率和生存率，也许可以通过优化免疫治疗的时间来实现。
澳大利亚和新西兰临床试验注册处 ANZCTRN12605000425695。
