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

• Published in: Journal for immunotherapy of cancer 2019-12, Vol.7 (1), p.337-337, Article 337
• Main 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
• Format: Article
• Language: English
• Subjects: Autoimmune diseases; Cancer; Cancer therapies; Carcinoma; Care and treatment; Clinical medicine; Clinical/Translational Cancer Immunotherapy; Committees; Development and progression; Encephalitis; Health aspects; Immunotherapy; Kidney cancer; Life Sciences; Lung cancer; Melanoma; Non-small cell lung cancer; Patient monitoring equipment; Patients; Physicians; Research Article; Tumors
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1186/s40425-019-0821-8

BackgroundParaneoplastic 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.MethodsWe 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.FindingsOf 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.InterpretationOur 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.