Patterns of radiological response to tebentafusp in patients with metastatic uveal melanoma.

IF 1.5 4区 医学 Q3 DERMATOLOGY Melanoma Research Pub Date : 2024-04-01 Epub Date: 2023-12-19 DOI:10.1097/CMR.0000000000000952
Natalia M Roshardt Prieto, Patrick Turko, Caroline Zellweger, Thi Dan Linh Nguyen-Kim, Ramon Staeger, Elisa Bellini, Mitchell P Levesque, Reinhard Dummer, Egle Ramelyte
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Abstract

Metastatic uveal melanoma (mUM) is a rare type of melanoma with poor outcomes. The first systemic treatment to significantly prolong overall survival (OS) in patients with mUM was tebentafusp, a bispecific protein that can redirect T-cells to gp-100 positive cells. However, the objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) may underestimate the clinical impact of tebentafusp. As metabolic response assessed by PET Response Criteria in Solid Tumors (PERCIST) has been reported to better correlate with clinical outcome, we here compared the patterns of radiological and morphological responses in HLA-A*02:01-positive patients with mUM treated with tebentafusp. In the 19 enrolled patients, RECIST showed an overall response rate (ORR) of 10%, median progression-free survival of 2.8 months (95% CI 2.5-8.4), and median OS (mOS) of 18.8 months. In 10 patients, where both RECIST and PERCIST evaluation was available, the ORR was 10% for both; however, the PFS was longer for PERCIST compared to RECIST, 3.1 and 2.4 months, respectively. A poor agreement between the criteria was observed at all assessments (Cohen's kappa ≤0), yet they differed significantly only at the first on-treatment imaging ( P  = 0.037). Elevated baseline LDH and age were associated with an increased risk for RECIST progression, while lymphocyte decrease after the first infusions correlated to reduced risk of RECIST progression. Detectable ctDNA at baseline did not correlate with progression. Early response to tebentafusp may be incompletely captured by conventional imaging, leading to a need to consider both tumor morphology and metabolism.

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转移性葡萄膜黑色素瘤患者对替本福明的放射学反应模式。
转移性葡萄膜黑色素瘤(mUM)是一种罕见的黑色素瘤,治疗效果不佳。特本芴素是一种双特异性蛋白,可将T细胞重定向至gp-100阳性细胞。然而,根据《实体瘤反应评估标准》(RECIST)得出的客观反应率可能低估了替本福司普的临床效果。据报道,实体瘤 PET 反应标准(PERCIST)评估的代谢反应与临床结果的相关性更好,因此我们在此比较了接受替本福斯治疗的 HLA-A*02:01 阳性 mUM 患者的放射学和形态学反应模式。在 19 例入组患者中,RECIST 显示总反应率 (ORR) 为 10%,中位无进展生存期为 2.8 个月(95% CI 2.5-8.4),中位 OS (mOS) 为 18.8 个月。在10例同时接受RECIST和PERCIST评估的患者中,两者的ORR均为10%;但与RECIST相比,PERCIST的PFS更长,分别为3.1个月和2.4个月。在所有评估中均观察到标准之间的一致性较差(Cohen's kappa ≤0),但它们仅在首次治疗造影时存在显著差异(P = 0.037)。基线LDH升高和年龄与RECIST进展风险增加有关,而首次输液后淋巴细胞减少与RECIST进展风险降低有关。基线时可检测到的ctDNA与病情进展无关。传统的成像方法可能无法完全捕捉到特本福斯普的早期反应,因此需要同时考虑肿瘤的形态和代谢。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Melanoma Research
Melanoma Research 医学-皮肤病学
CiteScore
3.40
自引率
4.50%
发文量
139
审稿时长
6-12 weeks
期刊介绍: ​​​​​​Melanoma Research is a well established international forum for the dissemination of new findings relating to melanoma. The aim of the Journal is to promote the level of informational exchange between those engaged in the field. Melanoma Research aims to encourage an informed and balanced view of experimental and clinical research and extend and stimulate communication and exchange of knowledge between investigators with differing areas of expertise. This will foster the development of translational research. The reporting of new clinical results and the effect and toxicity of new therapeutic agents and immunotherapy will be given emphasis by rapid publication of Short Communications. ​Thus, Melanoma Research seeks to present a coherent and up-to-date account of all aspects of investigations pertinent to melanoma. Consequently the scope of the Journal is broad, embracing the entire range of studies from fundamental and applied research in such subject areas as genetics, molecular biology, biochemistry, cell biology, photobiology, pathology, immunology, and advances in clinical oncology influencing the prevention, diagnosis and treatment of melanoma.
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