CPIs in patients with CKD/dialysis, systemic diseases with renal involvement, and solid organ transplant recipients
CPIs are large molecules, not removed by the kidneys, and thus not requiring dose adjustment related to the level of renal function. Nevertheless, there is a notable paucity of studies on the effects of CPIs in patients with renal dysfunction thus necessitating further investigations of this subject.
Other important issues to consider with CPIs are their safety and efficacy in patients with preexisting autoimmune disease. One nationwide multicenter study which included 112 patients with psoriasis, rheumatoid arthritis, and inflammatory bowel disease receiving CPIs indicated that flares or immune-related adverse events occur frequently, but are mostly manageable without discontinuation of cancer therapy. Immunosuppressive therapy at baseline was associated with poorer outcomes in this study (11). A more recent review suggests that the risk of developing immune-related adverse events depends on the underlying systemic disease. Patients with polymyalgia rheumatica, myasthenia and/or myositis, rheumatoid arthritis and psoriasis seem to be most affected, while those with lupus and ANCA-associated vasculitis are less inclined to experience immune-related adverse events with CPIs (2). However, larger studies are needed to substantiate this evidence.
Solid organ transplant recipients exhibit two to three-fold higher mortality and cancer risks than the general population. Nonetheless, anti-cancer treatment with CPIs in these patients is highly challenging. CPIs target The PD1/PDL1 axis involved in graft maintenance and may lead to stimulation of T-cells in peripheral tissues beyond cancer, thus affecting graft survival. Indeed, the use of CPIs has been associated with acute rejections of solid organ transplants in nearly half of the treated patients, with a slightly higher risk associated with PD1/PDL1- than with CLTA4 inhibitors. Conversely, immune-related adverse events are more often associated with CTLA4 CPIs (12, 13). Nevertheless, careful patient selection might improve the prospects and obtain a favorable antitumor response while avoiding rejection, but more studies are needed to define guidance on how to identify these patients (14, 16).