晚期黑色素瘤患者对免疫检查点抑制剂的影像学反应：一项回顾性观察性队列研究。
Imaging response to immune checkpoint inhibitors in patients with advanced melanoma: a retrospective observational cohort study.
作者信息
Gupta Mehul, Stukalin Igor, Meyers Daniel E, Heng Daniel Y C, Monzon Jose, Cheng Tina, Navani Vishal
机构信息
Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Tom Baker Cancer Centre, Calgary, AB, Canada.
出版信息
Front Oncol. 2024 May 31;14:1385425. doi: 10.3389/fonc.2024.1385425. eCollection 2024.
BACKGROUND
The association between objective imaging response and first line immune checkpoint inhibitor (ICI) therapy regimes in advanced melanoma remains uncharacterized in routine practice.
METHODS
We conducted a multi-center retrospective cohort analysis of advanced melanoma patients receiving first line ICI therapy from August 2013-May 2020 in Alberta, Canada. The primary outcome was likelihood of RECIST v1.1 assessed objective imaging response between patients receiving anti-programmed cell death protein 1 (anti-PD1) monotherapy and those receiving combination ipilimumab-nivolumab. Secondary outcomes were identification of baseline characteristics associated with non-response and the association of imaging response with overall survival (OS) and time to next treatment (TTNT).
RESULTS
198 patients were included, 41/198 (20.7%) had complete response, 86/198 (43.4%) had partial response, 23/198 (11.6%) had stable disease, and 48/198 (24.2%) had progressive disease. Median OS was not reached (NR) (95% CI 49.0-NR) months for complete responders, NR (95%CI 52.9-NR) months for partial responders, 33.7 (95%CI 15.8-NR) months for stable disease, and 6.4 (95%CI 5.2-10.1) months for progressive disease (log-rank p<0.001). Likelihood of objective imaging response remained similar between anti-PD1 monotherapy and ipilimumab-nivolumab groups (OR 1.95 95%CI 0.85-4.63, p=0.121). Elevated LDH level (OR 0.46; 95%CI 0.21-0.98, p=0.043), mucosal primary site (OR 0.14; 95%CI 0.03-0.48, p=0.003), and BRAF V600E mutation status (OR 0.31; 95%CI 0.13-0.72, p=0.007) were associated with decreased likelihood of response.
CONCLUSION
No significant difference in likelihood of imaging response between anti-PD1 monotherapy and combination ipilimumab-nivolumab was observed. Elevated LDH level, mucosal primary site, and BRAF V600E mutation status were associated with decreased likelihood of response. Given that pivotal clinical trials of ipilimumab-nivolumab did not formally compare ipilimumab-nivolumab with nivolumab monotherapy, this work adds context to differences in outcomes when these agents are used. These results may inform treatment selection, and aid in counseling of patients treated with first-line ICI therapy in routine clinical practice settings.
背景
在常规临床实践中，晚期黑色素瘤的客观影像学反应与一线免疫检查点抑制剂（ICI）治疗方案之间的关联仍未明确。
方法
我们对2013年8月至2020年5月在加拿大艾伯塔省接受一线ICI治疗的晚期黑色素瘤患者进行了一项多中心回顾性队列分析。主要结局是接受抗程序性细胞死亡蛋白1（抗PD1）单药治疗的患者与接受伊匹木单抗-纳武单抗联合治疗的患者之间，根据RECIST v1.1评估的客观影像学反应的可能性。次要结局是确定与无反应相关的基线特征，以及影像学反应与总生存期（OS）和下次治疗时间（TTNT）之间的关联。
结果
共纳入198例患者，其中41/198（20.7%）为完全缓解，86/198（43.4%）为部分缓解，23/198（11.6%）为疾病稳定，48/198（24.2%）为疾病进展。完全缓解者的中位OS未达到（NR）（95%CI 49.0-NR）个月，部分缓解者为NR（95%CI 52.9-NR）个月，疾病稳定者为33.7（95%CI 15.8-NR）个月，疾病进展者为6.4（95%CI 5.2-10.1）个月（对数秩检验p<0.001）。抗PD1单药治疗组和伊匹木单抗-纳武单抗组的客观影像学反应可能性仍然相似（OR 1.95，95%CI 0.85-4.63，p=0.121）。乳酸脱氢酶（LDH）水平升高（OR 0.46；95%CI 0.21-0.98，p=0.043）、黏膜原发部位（OR 0.14；95%CI 0.03-0.48，p=0.003）和BRAF V600E突变状态（OR 0.31；95%CI 0.13-0.72，p=0.007）与反应可能性降低相关。
结论
未观察到抗PD1单药治疗与伊匹木单抗-纳武单抗联合治疗在影像学反应可能性上的显著差异。LDH水平升高、黏膜原发部位和BRAF V600E突变状态与反应可能性降低相关。鉴于伊匹木单抗-纳武单抗的关键临床试验未正式将伊匹木单抗-纳武单抗与纳武单抗单药治疗进行比较，这项研究为这些药物使用时的结局差异提供了背景信息。这些结果可能为治疗选择提供参考，并有助于在常规临床实践中为接受一线ICI治疗的患者提供咨询。
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