Systemic lupus erythematosus reactivation after chemoimmunotherapy in preexisting autoimmune disease

Abstract

The use of immune checkpoint inhibitors (ICIs) offers new possibilities in modern treatment of many types of cancers. Few data regarding safety and efficacy of ICIs are available, and are mainly from retrospective studies and case reports rather than from clinical trials, in the context of preexisting autoimmune disease, mainly due to the risk of severe toxicity. We present an unexpected life-threatening reactivation of systemic lupus erythematosus after one dose of chemo-immunotherapy with pembrolizumab for oligometastatic non-small-cell lung cancer. We analyze data coming from the published literature in this setting and discuss the risk–benefit balance of immunotherapy in patients with preexisting severe autoimmune disease.

Immune Checkpoint Inhibitors and Lupus Erythematosus

“…There is one report of a severe SLE flare in the setting of pembrolizumab treatment [ 56 ]. This patient had a history of severe disease manifestations, including seizures and renal involvement, though at the time, was well controlled with mild arthralgias [ 56 ]. There are two reports of DLE in the literature [ 53 , 57 ].…”

“…In contrast to the case reported by Blakeway et al, this patient’s DLE had not required immunosuppressive therapy before ICI initiation. Among all studies and case reports of patients with autoimmune diseases on ICIs, a total of 27 patients had lupus [ 53 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ]. Unfortunately, reported demographics, details on disease activity, current lupus therapy, and other characteristics of this group are sparse.…”

“…Of these higher grade irAEs, one patient with DLE developed grade 3 central diabetes insipidus, while a separate patient with SLE was diagnosed with grade 4 immune thrombocytopenia (ITP) [ 56 , 58 ]. Of interest, the individual who developed ITP was also one of the patients with a grade 3 lupus flare, and had a history of severe lupus manifestations, including neurologic involvement, Libman–Sacks endocarditis, and renal involvement, amongst others [ 56 ]. Two patients developed both a lupus flare and a new irAE simultaneously [ 56 , 60 ].…”

Bullous pemphigoid exacerbated by nivolumab and temporally rescued with therapeutic plasma exchange

“…However, the Although IrAEs typically occur after several weeks from the first ICI administration in patients without preexisting autoimmune disease, preexisting systemic lupus erythematosus (SLE) was reported to worsen immediately after the first administration of pembrolizumab. 3 ICI-induced BP has been reported to persist even after discontinuing ICI because of continued immune activation. 4 This suggests that the continued immune activation related to ICI leads to poor control of preexisting autoimmune disease.…”

“…5 Thus, TPE may be a choice for the treatment of ICIexacerbated corticosteroid-refractory BP. ICI-administered patients with autoimmune disorders, including BP, MG, 1 and SLE, 3 will increase. Our experience may be useful, when physicians monitor ICI-treated patients with an autoimmune bullous disorder.…”