Ipilimumab administered to metastatic melanoma patients who progressed after dendritic cell vaccination.
Ipilimumab administered to metastatic melanoma patients who progressed after dendritic cell vaccination.
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DOI：
10.1080/2162402x.2016.1201625
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发表时间：
2016-08
期刊：
影响因子：
7.2
通讯作者：
Gerritsen WR
中科院分区：
文献类型：
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作者：
Boudewijns S;Koornstra RH;Westdorp H;Schreibelt G;van den Eertwegh AJ;Geukes Foppen MH;Haanen JB;de Vries IJ;Figdor CG;Bol KF;Gerritsen WR
背景：伊匹单抗已被证明对转移性黑色素瘤患者有效。本研究的目的是确定易普利姆玛在实验性树突状细胞（DC）疫苗接种后显示疾病进展的晚期黑色素瘤患者中的疗效。研究方法：回顾性分析48例IV期黑色素瘤患者在治疗早期DC疫苗接种后进展后接受伊匹单抗治疗。给予DC疫苗接种作为III期疾病（n = 18）或IV期疾病（n = 30）的辅助治疗。伊匹单抗（3 mg/kg）每3周一次给药，最多4个周期。结果：DC疫苗接种后进展与首次给予伊匹单抗之间的中位时间为5.4个月。在辅助DC疫苗接种后接受伊匹单抗的患者和接受DC疫苗接种治疗IV期黑色素瘤的患者的无进展生存（PFS）率在1年时为35%和7%，在2年时为35%和3%，而中位PFS分别为2.9个月和3.1个月。对于III期黑色素瘤，用辅助DC疫苗接种预治疗的患者的中位总生存期未达到，而对于IV期疾病，用DC疫苗接种预治疗的组中的中位总生存期为8.0个月（95%CI，5.2-10.9）（死亡的HR，0.36; p = 0.017）。19%的患者发生3级免疫相关不良事件，1例死亡（2%）与ipilimumab有关。结论：在相当数量的晚期黑色素瘤患者中发现了对伊匹单抗的临床应答，这些患者在针对III期疾病的辅助DC疫苗接种后出现进展，而在针对IV期疾病的DC疫苗接种后显示出进展的患者中，伊匹单抗的效果非常有限。
Background: Ipilimumab has proven to be effective in metastatic melanoma patients. The purpose of this study was to determine the efficacy of ipilimumab in advanced melanoma patients who showed progressive disease upon experimental dendritic cell (DC) vaccination. Methods: Retrospective analysis of 48 stage IV melanoma patients treated with ipilimumab after progression upon DC vaccination earlier in their treatment. DC vaccination was given either as adjuvant treatment for stage III disease (n = 18) or for stage IV disease (n = 30). Ipilimumab (3 mg/kg) was administered every 3 weeks for up to 4 cycles. Results: Median time between progression upon DC vaccination and first gift of ipilimumab was 5.4 mo. Progression-free survival (PFS) rates for patients that received ipilimumab after adjuvant DC vaccination, and patients that received DC vaccination for stage IV melanoma, were 35% and 7% at 1 y and 35% and 3% at 2 y, while the median PFS was 2.9 mo and 3.1 mo, respectively. Median overall survival of patients pre-treated with adjuvant DC vaccination for stage III melanoma was not reached versus 8.0 mo (95% CI, 5.2–10.9) in the group pre-treated with DC vaccination for stage IV disease (HR of death, 0.36; p = 0.017). Grade 3 immune-related adverse events occurred in 19% of patients and one death (2%) was related to ipilimumab. Conclusions: Clinical responses to ipilimumab were found in a considerable number of advanced melanoma patients with progression after adjuvant DC vaccination for stage III disease, while the effect was very limited in patients who showed progression after DC vaccination for stage IV disease.