TY - JOUR T1 - Worsening and newly diagnosed paraneoplastic syndromes following anti-PD-1 or anti-PD-L1 immunotherapies, a descriptive study JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1186/s40425-019-0821-8 VL - 7 IS - 1 SP - 337 AU - Guillaume Manson AU - Alexandre Thibault Jacques Maria AU - Florence Poizeau AU - François-Xavier Danlos AU - Marie Kostine AU - Solenn Brosseau AU - Sandrine Aspeslagh AU - Pauline Du Rusquec AU - Maxime Roger AU - Maud Pallix-Guyot AU - Marc Ruivard AU - Léa Dousset AU - Laurianne Grignou AU - Dimitri Psimaras AU - Johan Pluvy AU - Gilles Quéré AU - Franck Grados AU - Fanny Duval AU - Frederic Bourdain AU - Gwenola Maigne AU - Julie Perrin AU - Benoit Godbert AU - Beatris Irina Taifas AU - Alexandra Forestier AU - Anne-Laure Voisin AU - Patricia Martin-Romano AU - Capucine Baldini AU - Aurélien Marabelle AU - Christophe Massard AU - Jérôme Honnorat AU - Olivier Lambotte AU - Jean-Marie Michot Y1 - 2019/12/01 UR - http://jitc.bmj.com/content/7/1/337.abstract N2 - 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. ER -