Center for Dermato-Oncology, Department of Dermatology, Eberhard Karls University of Tuebingen, Liebermeisterstrasse 25, 72076, Tuebingen, Germany.
Cluster of Excellence iFIT (EXC 2180), Tuebingen, Germany.
Am J Clin Dermatol. 2023 May;24(3):453-467. doi: 10.1007/s40257-023-00775-7. Epub 2023 May 4.
Immune checkpoint inhibition (ICI) has changed the melanoma treatment spectrum. Few studies have examined the characteristics and long-term outcomes of patients achieving complete response (CR) under ICI.
We evaluated patients with unresectable stage IV melanoma treated with first-line ICI. The characteristics of those achieving CR were compared with those not achieving CR. Progression-free survival (PFS) and overall survival (OS) were assessed. Late-onset toxicities, response to second-line treatment, the prognostic value of clinicopathologic features, and blood markers were examined.
A total of 265 patients were included; 41 (15.5%) achieved CR, while 224 (84.5%) had progressive disease, stable disease, or partial response. At the therapy start, those who had CR were more likely to be older than 65 years of age (p = 0.013), have a platelet-to-lymphocyte ratio below 213 (p = 0.036), and have lower lactate dehydrogenase levels (p = 0.008) than those not achieving a CR. For those who discontinued therapy after CR, the median follow-up time after CR was 56 months (interquartile range [IQR] 52-58) and the median time from CR to therapy end was 10 months (IQR 1-17). Five-year PFS after CR was 79% and 5-year OS was 83%. Most complete responders had a normalization of S100 at the time of CR (p < 0.001). In simple Cox regression analysis, age below 77 years at CR (p = 0.04) was associated with better prognosis after CR. Eight patients received second-line ICI; disease control was seen in 63%. Late immune-related toxicities occurred in 25% of patients, most being cutaneous immune-related toxicities.
Response, according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, is, until now, the most important prognostic factor, and CR is a valid surrogate marker for long-term survival in patients treated with ICI. Our results highlight the importance of investigating the optimal therapy duration in complete responders.
免疫检查点抑制（ICI）改变了黑色素瘤的治疗范围。很少有研究检查过在 ICI 下达到完全缓解（CR）的患者的特征和长期结果。
我们评估了接受一线 ICI 治疗的不可切除的 IV 期黑色素瘤患者。比较了达到 CR 的患者与未达到 CR 的患者的特征。评估无进展生存期（PFS）和总生存期（OS）。检查迟发性毒性、二线治疗反应、临床病理特征的预后价值和血液标志物。
共纳入 265 例患者；41 例（15.5%）达到 CR，224 例（84.5%）疾病进展、稳定或部分缓解。在治疗开始时，达到 CR 的患者年龄大于 65 岁的可能性更高（p=0.013），血小板与淋巴细胞比值低于 213（p=0.036），乳酸脱氢酶水平更低（p=0.008）。对于那些在 CR 后停止治疗的患者，CR 后中位随访时间为 56 个月（IQR 52-58），CR 至治疗结束的中位时间为 10 个月（IQR 1-17）。CR 后的 5 年 PFS 为 79%，5 年 OS 为 83%。大多数完全缓解者在 CR 时 S100 正常（p<0.001）。在简单的 Cox 回归分析中，CR 时年龄低于 77 岁（p=0.04）与 CR 后预后较好相关。8 例患者接受二线 ICI；63%疾病得到控制。25%的患者出现迟发性免疫相关毒性，大多数为皮肤免疫相关毒性。
根据实体瘤反应评估标准（RECIST），反应仍然是最重要的预后因素，CR 是接受 ICI 治疗的患者长期生存的有效替代标志物。我们的结果强调了研究完全缓解者最佳治疗持续时间的重要性。
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