Worsening and newly diagnosed paraneoplastic syndromes following anti-PD-1 or anti-PD-L1 immunotherapies, a descriptive study. Issue 1 (3rd December 2019)

• Record Type: Journal Article
• Authors: 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;
• Is Part Of: Journal for immunotherapy of cancer. Volume 7:Issue 1(2019)
• Publication Date: 2019-12-03
• Subjects: Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1186/s40425-019-0821-8
• Languages: English
• ISSNs: 2051-1426

Abstract

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.