Worsening and newly diagnosed paraneoplastic syndromes following anti-PD-1 or anti-PD-L1 immunotherapies, a descriptive study.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Manson Guillaume, Maria Alexandre Thibault Jacques, Poizeau Florence, Danlos François-Xavier, Kostine Marie, Brosseau Solenn, Aspeslagh Sandrine, Du Rusquec Pauline, Roger Maxime, Pallix-Guyot Maud, Ruivard Marc, Dousset Léa, Grignou Laurianne, Psimaras Dimitri, Pluvy Johan, Quéré Gilles, Grados Franck, Duval Fanny, Bourdain Frederic, Maigne Gwenola, Perrin Julie, Godbert Benoit, Taifas Beatris Irina, Forestier Alexandra, Voisin Anne-Laure, Martin-Romano Patricia, Baldini Capucine, Marabelle Aurélien, Massard Christophe, Honnorat Jérôme, Lambotte Olivier, Michot Jean-Marie
Аннотация
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.