Prognostic Hematologic Biomarkers Following Immune Checkpoint Inhibition in Metastatic Uveal Melanoma.
Prognostic Hematologic Biomarkers Following Immune Checkpoint Inhibition in Metastatic Uveal Melanoma.
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葡萄膜黑色素瘤是一种罕见的黑色素瘤，但却是眼部最常见的肿瘤。尽管对最初的肿瘤有有效的治疗方法，但许多患者的癌症会扩散到远处的身体部位。治疗转移性疾病没有统一的方法，但医生经常使用利用患者免疫系统的治疗方法，因为这些治疗方法对其他类型的黑色素瘤非常有效。然而，并非所有患者都对这种疗法有反应，有些患者会出现与治疗相关的毒性。本文的目的是确定可能有助于确定早期治疗反应的特征或血液标志物。具体来说，我们分析了一种叫做乳酸脱氢酶（LDH）的分子，以及治疗开始时和治疗开始后2个月不同白细胞的比例。我们发现这些非侵入性血液标记物在确定哪些患者对治疗有反应方面很有用。背景：转移性葡萄膜黑色素瘤（MUM）没有标准化的治疗方法，但免疫检查点抑制剂（ICI）的使用越来越多。虽然ICI改变了转移性皮肤黑色素瘤的生存，但MUM患者并没有同样受益。已知影响ICI反应的因素包括血液学指标、乳酸脱氢酶（LDH）和中性粒细胞：淋巴细胞比率（NLR）。我们评估了LDH和NLR在ICI开始和MUM治疗时的预后价值。方法：2006年8月至2022年5月期间，对MUM患者进行伊匹单抗/纳武单抗或伊匹单抗/纳武单抗/派姆单抗单药治疗。采用单变量（UVA）和多变量（MVA）分析来评估预定义基线因素对无进展（PFS）和总生存期（OS）的预后价值。结果：在46例接受ICI治疗的MUM患者中，基线和治疗时LDH升高是OS的预后因素(ICI开始，HR (95% CI): 3.6 (1.9-7.0), p < 0.01；治疗中，HR （95% CI): 3.7 (1.6-8.8), p < 0.01）和PFS (ICI开始，HR (95% CI): 2.8 (1.5-5.4), p < 0.0001)；治疗期LDH (HR （95% CI): 2.2 (1.1 ~ 4.3), p < 0.01）。治疗期间NLR是PFS的预后因素(HR （95% CI): 1.9 (1.0-3.9), p < 0.01）。治疗期间LDH仍然是MVA患者生存的重要因素(OS: HR (95% CI): 1.001 (1.00-1.002), p < 0.05)；PFS: HR （95% CI): 1.001 (1.00-1.002), p < 0.01）。结论：本研究表明LDH和NLR可用于ICI治疗MUM患者的预后。需要进一步的研究来证实这些和其他预后生物标志物的重要性。
Uveal melanoma is a rare form of melanoma but is the most common tumor in the eye. Despite having effective treatments for the initial tumor, many patients experience the spread of their cancer to distant body sites. There is no uniform way of treating metastatic disease, but physicians often use therapies that harness the patient’s immune system because these same treatments have been very effective in other types of melanoma. Not all patients respond to this therapy though, and some develop toxicity related to the treatment. The goal of this paper was to identify features or blood markers that may help determine response to treatment early. Specifically, we analyzed a molecule called lactate dehydrogenase (LDH) and the ratio of different white blood cells at the start of therapy and 2 months after treatment was started. We found that these non-invasive blood markers could be useful in determining which patients are responding to treatment. Background: There is no standardized treatment for metastatic uveal melanoma (MUM) but immune checkpoint inhibitors (ICI) are increasingly used. While ICI has transformed the survival of metastatic cutaneous melanoma, MUM patients do not equally benefit. Factors known to affect ICI response include the hematologic markers, lactate dehydrogenase (LDH) and neutrophil:lymphocyte ratio (NLR). We evaluated the prognostic value of LDH and NLR at the start of ICI and on treatment in MUM. Methods: MUM patients were treated between August 2006 and May 2022 with combination ipilimumab/nivolumab or ipilimumab/nivolumab/pembrolizumab single-agent therapy. Univariable (UVA) and multivariable (MVA) analyses were used to assess the prognostic value of predefined baseline factors on progression-free (PFS) and overall survival (OS). Results: In forty-six patients with MUM treated with ICI, elevated baseline and on-treatment LDH was prognostic for OS (start of ICI, HR (95% CI): 3.6 (1.9–7.0), p < 0.01; on-treatment, HR (95% CI): 3.7 (1.6–8.8), p < 0.01) and PFS (start of ICI, (HR (95% CI): 2.8 (1.5–5.4), p < 0.0001); on-treatment LDH (HR (95% CI): 2.2 (1.1–4.3), p < 0.01). On-treatment NLR was prognostic for PFS (HR (95% CI): 1.9 (1.0–3.9), p < 0.01). On-treatment LDH remained an important contributor to survival on MVA (OS: HR (95% CI): 1.001 (1.00–1.002), p < 0.05); PFS: HR (95% CI): 1.001 (1.00–1.002), p < 0.01). Conclusions: This study demonstrates that LDH and NLR could be useful in the prognostication of MUM patients treated with ICI. Additional studies are needed to confirm the importance of these and other prognostic biomarkers.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
基线嗜中性粒细胞与淋巴细胞比率与经ipilmimab治疗的转移性黑色素瘤患者的结果有关。
影响因子：
8.8
作者：
Ferrucci PF;Gandini S;Battaglia A;Alfieri S;Di Giacomo AM;Giannarelli D;Cappellini GC;De Galitiis F;Marchetti P;Amato G;Lazzeri A;Pala L;Cocorocchio E;Martinoli C
通讯作者：
Martinoli C
DOI：
10.2147/opth.s89591
发表时间：
2017
期刊：
Clinical ophthalmology (Auckland, N.Z.)
影响因子：
--
作者：
Krantz BA;Dave N;Komatsubara KM;Marr BP;Carvajal RD
通讯作者：
Carvajal RD
DOI：
10.1016/j.lungcan.2021.11.021
发表时间：
2022-01
期刊：
Lung cancer (Amsterdam, Netherlands)
影响因子：
--
作者：
Bryant AK;Sankar K;Strohbehn GW;Zhao L;Elliott D;Qin A;Yentz S;Ramnath N;Green MD
通讯作者：
Green MD