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Worsening and newly diagnosed paraneoplastic syndromes following anti-PD-1 or anti-PD-L1 immunotherapies, a descriptive study

Guillaume Manson 1, 2 Alexandre Thibault Jacques Maria 3 Florence Poizeau 1 François-Xavier Danlos 2 Marie Kostine 4 Solenn Brosseau 5 Sandrine Aspeslagh 6 Pauline Du Rusquec 7 Maxime Roger 8, 9 Maud Pallix-Guyot 10 Marc Ruivard 11 Léa Dousset 12 Laurianne Grignou 13 Dimitri Psimaras 14 Johan Pluvy 5 Gilles Quéré 15 Franck Grados 16 Fanny Duval 17 Frédéric Bourdain 18, 19 Gwénola Maigné 20 Julie Perrin 21 Benoit Godbert 22 Beatris Irina Taifas 23 Alexandra Forestier 24 Anne-Laure Voisin 2 Patricia Martin-Romano 2 Capucine Baldini 25, 2 Aurélien Marabelle 26, 2 Christophe Massard 27, 2 Jérôme Honnorat 28, 29 Olivier Lambotte 30, 31 Jean-Marie Michot 31, 2
Abstract : BACKGROUND: Paraneoplastic syndromes (PNS) are autoimmune disorders specifically associated with cancer. There are few data on anti-PD-1 or anti-PD-L1 immunotherapy in patients with a PNS. Our objective was to describe the outcome for patients with a pre-existing or newly diagnosed PNS following the initiation of anti-PD-1 or anti-PD-L1 immunotherapy. METHODS: We included all adult patients (aged ≥18) treated with anti-PD-1 or anti-PD-L1 immunotherapy for a solid tumor, diagnosed with a PNS, and registered in French pharmacovigilance databases. Patients were allocated to cohorts 1 and 2 if the PNS had been diagnosed before vs. after the initiation of immunotherapy, respectively. FINDINGS: Of the 1304 adult patients screened between June 27th, 2014, and January 2nd, 2019, 32 (2.45%) had a PNS and were allocated to either cohort 1 (n = 16) or cohort 2 (n = 16). The median (range) age was 64 (45-88). The tumor types were non-small-cell lung cancer (n = 15, 47%), melanoma (n = 6, 19%), renal carcinoma (n = 3, 9%), and other malignancies (n = 8, 25%). Eleven (34%) patients presented with a neurologic PNS, nine (28%) had a rheumatologic PNS, eight (25%) had a connective tissue PNS, and four (13%) had other types of PNS. The highest severity grade for the PNS was 1-2 in 10 patients (31%) and ≥ 3 in 22 patients (69%). Four patients (13%) died as a result of the progression of a neurologic PNS (encephalitis in three cases, and Lambert-Eaton syndrome in one case). Following the initiation of immunotherapy, the PNS symptoms worsened in eight (50%) of the 16 patients in cohort 1. INTERPRETATION: Our results show that PNSs tend to be worsened or revealed by anti-PD-1 or anti-PD-L1 immunotherapy. Cases of paraneoplastic encephalitis are of notable concern, in view of their severity. When initiating immunotherapy, physicians should carefully monitor patients with a pre-existing PNS.
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https://hal.umontpellier.fr/hal-02530293
Contributeur : Nathalie Salvy-Cordoba <>
Soumis le : jeudi 2 avril 2020 - 18:58:10
Dernière modification le : vendredi 15 mai 2020 - 12:22:08

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Guillaume Manson, Alexandre Thibault Jacques Maria, Florence Poizeau, François-Xavier Danlos, Marie Kostine, et al.. Worsening and newly diagnosed paraneoplastic syndromes following anti-PD-1 or anti-PD-L1 immunotherapies, a descriptive study. Journal for Immunotherapy of Cancer, London : BioMed Central, 2013-, 2019, 7 (1), ⟨10.1186/s40425-019-0821-8⟩. ⟨hal-02530293⟩

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