Netherlands Cancer Institute NKI-AVL, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands,
Cancer Immunol Immunother. 2014 May;63(5):449-58. doi: 10.1007/s00262-014-1528-9. Epub 2014 Mar 8.
Ipilimumab, a cytotoxic T lymphocyte-associated antigen-4 blocking antibody, has improved overall survival (OS) in metastatic melanoma in phase III trials. However, about 80 % of patients fail to respond, and no predictive markers for benefit from therapy have been identified. We analysed a 'real world' population of patients treated with ipilimumab to identify markers for treatment benefit.
Patients with advanced cutaneous melanoma were treated in the Netherlands (NL) and the United Kingdom (UK) with ipilimumab at 3 mg/kg. Baseline characteristics and peripheral blood parameters were assessed, and patients were monitored for the occurrence of adverse events and outcomes.
A total of 166 patients were treated in the Netherlands. Best overall response and disease control rates were 17 and 35 %, respectively. Median follow-up was 17.9 months, with a median progression-free survival of 2.9 months. Median OS was 7.5 months, and OS at 1 year was 37.8 % and at 2 years was 22.9 %. In a multivariate model, baseline serum lactate dehydrogenase (LDH) was demonstrated to be the strongest predictive factor for OS. These findings were validated in an independent cohort of 64 patients from the UK.
In both the NL and UK cohorts, long-term benefit of ipilimumab treatment was unlikely for patients with baseline serum LDH greater than twice the upper limit of normal. In the absence of prospective data, clinicians treating melanoma may wish to consider the data presented here to guide patient selection for ipilimumab therapy.
细胞毒性 T 淋巴细胞相关抗原 4 阻断抗体伊匹单抗在 III 期临床试验中提高了转移性黑色素瘤的总生存期（OS）。然而，约 80%的患者对此治疗无反应，且尚未确定获益的预测标志物。我们分析了接受伊匹单抗治疗的“真实世界”患者人群，以确定治疗获益的标志物。
荷兰（NL）和英国（UK）的晚期皮肤黑色素瘤患者接受了 3 mg/kg 剂量的伊匹单抗治疗。评估了基线特征和外周血参数，并监测了不良事件和结局的发生情况。
共 166 例患者在荷兰接受了治疗。最佳总体缓解率和疾病控制率分别为 17%和 35%。中位随访时间为 17.9 个月，中位无进展生存期为 2.9 个月。中位总生存期为 7.5 个月，1 年总生存率为 37.8%，2 年总生存率为 22.9%。在多变量模型中，基线血清乳酸脱氢酶（LDH）被证明是 OS 的最强预测因素。这些发现在来自英国的 64 例独立队列中得到了验证。
在 NL 和 UK 队列中，基线血清 LDH 大于正常值上限两倍的患者接受伊匹单抗治疗的长期获益不太可能。在缺乏前瞻性数据的情况下，治疗黑色素瘤的临床医生可能希望考虑这里提供的数据来指导伊匹单抗治疗的患者选择。
