Abstract
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.
Highlights
Over the last 5 years, anti-programmed cell death protein (PD)-1 or anti-programmed death-ligand (L)-1 immunotherapy has proven to be highly effective in the treatment of various types of cancer
Little is known about the use of immune checkpoint inhibitor in patients with a Paraneoplastic syndromes (PNS), some recent data suggest that these syndromes are complications of immunotherapy [10,11,12,13]
Cohort 1 comprised patients diagnosed with a PNS prior to the initiation of anti-PD-1 or anti-PD-L1 immunotherapy, whereas cohort 2 comprised patients with a PNS diagnosed after the initiation of anti-PD-1 or anti-PD-L1 immunotherapy
Summary
Over the last 5 years, anti-programmed cell death protein (PD)-1 or anti-programmed death-ligand (L)-1 immunotherapy has proven to be highly effective in the treatment of various types of cancer. Paraneoplastic syndromes (PNSs) are rare autoimmune disorders associated with cancer [7, 8]. Little is known about the use of immune checkpoint inhibitor in patients with a PNS, some recent data suggest that these syndromes are complications of immunotherapy [10,11,12,13]. It is noteworthy that PNSs are generally associated with specific tumor types that are not routinely treated with immune checkpoint inhibitors; these include small-cell lung cancers [14], gynecological cancers [15], and thymic carcinomas [16]. A recent review of neurologic PNSs that occurred following treatment with immune checkpoint inhibitors emphasized the clinical seriousness of these syndromes and the need for further investigation in the context of immunotherapy [11]. 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
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