Acar Caner, Yüksel Haydar Çağatay, Şahin Gökhan, Açar Fatma Pinar, Tünbekici Salih, Çelebi Gülçin, Karaca Burçak
Division of Medical Oncology, Department of Internal Medicine, Ege University Medical Faculty, Izmir, 35100, Turkey.
Department of Internal Medicine, Ege University Medical Faculty, Izmir, Turkey, 35100.
Discov Oncol. 2024 Dec 20;15(1):813. doi: 10.1007/s12672-024-01702-w.
Immune checkpoint inhibitors (ICIs) have significantly improved the five-year survival rate for advanced melanoma. However, many patients exhibit resistance to ICI therapy. This study evaluated the efficacy and prognostic factors of anti-PD-1 (Group A) and nivolumab-ipilimumab (Group B) therapy in patients with advanced melanoma who were resistant to prior ICI therapy. We conducted a retrospective analysis of 56 patients with advanced melanoma who had previously shown resistance to ICI therapy. In the Group A (who have previously shown resistance to anti-CTLA-4, n = 28), the objective response rate (ORR) was 42.9%, with a disease control rate (DCR) of 53%. In the Group B (previously shown resistance to anti-PD-1, n = 28), the ORR was 17.9%, and the DCR was 25%. The ORR was lower in two subgroups: patients who showed progression or relapse in the the initial radiological assessment of prior ICI therapy (ORR 10.5%) and patients who had previously received ICI in the adjuvant setting (ORR 8.3%). A Royal Marsden Hospital (RMH) score of 2-3 was a predictor of OS in both groups (Group A: HR 3.789, 95% CI 1.356-10.589, p = 0.011; Group B: HR 4.281, 95% CI 1.490-12.300, p = 0.007) and for PFS in the Group B (HR 3.167, 95% CI 1.062-9.442, p = 0.039). Anti-PD-1 therapy demonstrated efficacy following resistance to anti-CTLA-4, whereas combination ICI therapy showed lower response rates in patients resistant to anti-PD-1. Further studies are needed to confirm the RMH scores and other prognostic markers and to evaluate subgroups with lower efficacy of nivolumab-ipilimumab therapy.
免疫检查点抑制剂（ICIs）显著提高了晚期黑色素瘤的五年生存率。然而，许多患者对ICI治疗表现出耐药性。本研究评估了抗PD-1治疗（A组）和纳武利尤单抗-伊匹木单抗联合治疗（B组）对先前ICI治疗耐药的晚期黑色素瘤患者的疗效和预后因素。我们对56例先前对ICI治疗耐药的晚期黑色素瘤患者进行了回顾性分析。在A组（先前对抗CTLA-4耐药，n = 28）中，客观缓解率（ORR）为42.9%，疾病控制率（DCR）为53%。在B组（先前对抗PD-1耐药，n = 28）中，ORR为17.9%，DCR为25%。在两个亚组中ORR较低：在先前ICI治疗的初始影像学评估中出现进展或复发的患者（ORR 10.5%）和先前在辅助治疗中接受过ICI治疗的患者（ORR 8.3%）。皇家马斯登医院（RMH）评分为2 - 3是两组总生存期（A组：HR 3.789，95%CI 1.356 - 10.589，p = 0.011；B组：HR 4.281，95%CI 1.490 - 12.300，p = 0.007）以及B组无进展生存期（HR 3.167，95%CI 1.
