Neeta Pandit-Taskar, Audrey Mauguen, Denise Frosina, Achim Jungbluth, Klaus J Busam, Serge Lyashchenko, Jazmin Schwartz, Parisa Momtaz, Allison Betof Warner, James W Smithy, Alexander N Shoushtari, Margaret K Callahan, Paul B Chapman, Michael A Postow
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引用次数: 0
Abstract
Programmed death ligand-1 (PD-L1) is an inducible protein heterogeneously expressed in melanoma. Assessment of PD-L1 expression is challenging and standard immunohistochemistry (IHC) requires biopsies and cannot capture heterogeneity of expression. Noninvasive imaging methods provide evaluation of expression across lesions in the body. We conducted a prospective pilot trial with PD-L1 PET imaging with [ 18 F]-BMS-986229 as a noninvasive approach to assess PD-L1 expression across lesions, in 10 patients with advanced melanoma, longitudinally during treatment with nivolumab and ipilimumab. PET imaging was performed at baseline and at 6 weeks after initiation of treatment. We examined the relationship of PD-L1 PET uptake to radiographic clinical response. [ 18 F]-BMS-986229 uptake was variably seen across lesions in patients at baseline. All patients showed positive uptake in lesions at baseline PET with a median SUV max of 3.6 (range: 1.7-8.6). PD-L1 PET SUV max decreased in all but two lesions 6 weeks after treatment initiation. Four of five patients had a mean (SUV max ) greater than or equal to 3.00 in Response Evaluation Criteria in Solid Tumors (RECIST) evaluable lesions at baseline, and all had a RECIST response while all progressors ( n = 3) had baseline PD-L1 mean SUV max less than or equal to 2.60. A higher lesional baseline SUV max was associated with greater individual lesion reduction during treatment. The PD-L1 uptake in lesions showed a low correlation with baseline PD-L1 by IHC. In this small pilot study, PD-L1 PET imaging using [ 18 F]-BMS-986229 showed feasibility in noninvasively assessing lesion uptake and PD-L1 heterogeneity in patients receiving combination immunotherapy. Future exploration of this tracer in larger patient cohorts is necessary to delineate its use in managing immunotherapy treatments.
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.