Bar-Hai Neta, Ben-Betzalel Guy, Stoff Ronen, Grynberg Shirly, Schachter Jacob, Shapira-Frommer Ronnie, Asher Nethanel
Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Ramat Gan 52621, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
Cancers (Basel). 2023 Jun 3;15(11):3041. doi: 10.3390/cancers15113041.
Successful treatment with Immune Checkpoint Inhibitors (ICI) requires the balanced activation of the immune system. Over-activation may result in immune-related adverse events (irAEs), which often require steroidal treatment. This study examined the possible impact of steroids on treatment efficacy in melanoma patients concerning initiation timing and dosage.
A retrospective, single-center analysis of patients with advanced melanoma who underwent first-line ICI therapy during 2014-2020 was conducted.
Among the 415 patients, two-hundred patients (48.3%) were exposed to steroids during the first line, most of them due to irAEs ( = 169, 84.5%). Nearly a quarter of them were exposed to steroids within the first four weeks of treatment. Surprisingly, steroidal exposure was associated with better progression-free survival (PFS; HR = 0.74, = 0.015); however, early exposure (within four weeks of treatment) resulted in a significantly shorter PFS compared to late exposure (adjusted HR 3.2, < 0.001).
Early exposure to corticosteroids during the priming phase of ICI therapy could impede the establishment of an effective immune response. These results suggest that caution should be exercised when considering the use of steroids for the management of early-onset irAEs.
免疫检查点抑制剂(ICI)的成功治疗需要免疫系统的平衡激活。过度激活可能导致免疫相关不良事件(irAE),这通常需要类固醇治疗。本研究探讨了类固醇在启动时间和剂量方面对黑色素瘤患者治疗效果的可能影响。
对2014年至2020年期间接受一线ICI治疗的晚期黑色素瘤患者进行回顾性单中心分析。
在415例患者中,200例(48.3%)在一线治疗期间接受了类固醇治疗,其中大多数是由于irAE(n = 169,84.5%)。近四分之一的患者在治疗的前四周内接受了类固醇治疗。令人惊讶的是,类固醇暴露与更好的无进展生存期(PFS)相关(HR = 0.74,P = 0.015);然而,与晚期暴露相比,早期暴露(治疗后四周内)导致PFS显著缩短(调整后HR 3.2,P < 0.001)。
在ICI治疗的启动阶段早期暴露于皮质类固醇可能会阻碍有效免疫反应的建立。这些结果表明,在考虑使用类固醇治疗早期发作的irAE时应谨慎。