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Pseudoprogression and Hyperprogression as New Forms of Response to Immunotherapy

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Abstract

Indications of immunotherapy in oncology are continuously expanding, and unconventional types of response have been observed with these new treatments. These include transient progressive disease followed by a partial response, described as pseudoprogression, that raises the question of treatment beyond progression; and rapid disease progression associated with clinical decline, reported as hyperprogression. However, there are currently no consensual definitions of these phenomena and their impact on daily practice remains unclear. We reviewed existing data on pseudoprogression and hyperprogression with a focus on the definitions, incidence, predictive factors, potential biological mechanisms, and methods published to help distinguish pseudoprogression from progression and hyperprogression. The incidence of pseudoprogression ranged from 0 to 15%, with some authors also including disease stabilization after a first progression. For hyperprogression, incidence ranged from 4 to 29% with various definitions, and several authors reported a correlation with worse survival. Both phenomena were observed in a large panel of cancer types. Several radiological and biological methods have been reported to help distinguish pseudoprogression from progression and hyperprogression, such as analysis of radiomics, and circulating-tumor DNA or cell-free DNA, but these need to be confirmed in larger prospective cohorts. In conclusion, pseudoprogression and hyperprogression are both frequent types of responses under immunotherapy, and there is a need to better characterize these to improve the management of cancer patients. Treatment beyond progression should always be considered with caution and necessitates close clinical monitoring. In case of suspected hyperprogression, immunotherapy should be stopped early.

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Authors and Affiliations

  1. Department of Drug Development and Innovation (D3i), Institut Curie, Saint-Cloud, Paris, France

    Maxime Frelaut, Pauline du Rusquec, Alexandre de Moura, Christophe Le Tourneau & Edith Borcoman

  2. INSERM U900 Research Unit, Saint-Cloud, France

    Christophe Le Tourneau

  3. Paris-Saclay University, Paris, France

    Christophe Le Tourneau

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  1. Maxime Frelaut
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  2. Pauline du Rusquec
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Correspondence to Edith Borcoman.

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Christophe Le Tourneau has participated in advisory boards from MSD, BMS, Merck Serono, Astra Zeneca, Roche, Novartis, Amgen, Nanobiotix, Celgene, and Rakuten. Maxime Frelaut, Pauline du Rusquec, Alexandre de Moura, and Edith Borcoman declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Frelaut, M., du Rusquec, P., de Moura, A. et al. Pseudoprogression and Hyperprogression as New Forms of Response to Immunotherapy. BioDrugs 34, 463–476 (2020). https://doi.org/10.1007/s40259-020-00425-y

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