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Background Patients with paraneoplastic syndromes (PNS) are excluded from clinical trials involving immune checkpoint inhibitors (ICIs) due to safety concerns. Moreover, real-world data on efficacy and safety is scarce.Methods In this retrospective study, data were collected on patients with PNS and solid tumors receiving ICI between 2015 and 2022 at nine institutions. Patients were classified into: Cohort 1 (pre-existing PNS before ICI initiation), cohort 2 (PNS during ICI treatment), and cohort 3 (PNS after ICI discontinuation). Patients with metastatic non-small cell lung cancer (NSCLC) (mNSCLC) from cohort 1 were matched to patients who were PNS-free at each institution up to a 1:3 ratio for age, sex, type of ICI, use of concurrent chemotherapy, and number of lines of systemic therapy prior to ICI initiation. Kaplan-Meier method was used to assess overall survival (OS) and time-to-next treatment (TTNT).Results Among 109 patients with PNS treated with ICIs, median age at ICI initiation was 67 years (IQR: 58–74). The most represented cancer type was NSCLC (n=39, 36%). In cohort 1 (n=55), PNS exacerbations occurred in 16 (29%) patients with median time to exacerbation after ICI of 1.1 months (IQR: 0.7–3.3). Exacerbation or de novo PNS prompted temporary/permanent interruption of ICIs in 14 (13%) patients. For cohort 2 (n=16), median time between ICI initiation and de novo PNS was 1.2 months (IQR: 0.4–3.5). Treatment-related adverse events (trAEs) occurred in 43 (39%) patients. Grade ≥3 trAEs occurred in 18 (17%) patients. PNS-directed immunosuppressive therapy was required in 55 (50%) patients. We matched 18 patients with mNSCLC and PNS (cohort 1) to 40 without PNS, treated with ICIs. There was no significant difference in OS or TTNT between patients with mNSCLC with and without PNS, although a trend was seen towards worse outcomes in patients with PNS. TrAEs occurred in 6/18 (33%) and 14/40 (35%), respectively. Grade ≥3 trAEs occurred in 4 (22%) patients with PNS and 7 (18%) patients without PNS.Conclusions Exacerbations of pre-existing PNS occurred in 29% of patients treated with ICIs and both exacerbations and de novo PNS occur early in the ICI course. TrAE from ICIs were similar between patients with and without PNS. Our data suggest that pre-existing PNS should not preclude consideration of ICI therapy although patients may not derive the same clinical benefit compared with patients without PNS.

Objective: Lipocalin 2 (LCN2 or NGAL), a protein derived from neutrophils, macrophages, adipocytes, and other cells, has been proposed to be a link between obesity and insulin resistance (IR), but animal and cross-sectional human studies have revealed conflicting results. We studied the association of serum lipocalin 2 with anthropometric, metabolic, and cardiovascular risk markers in young healthy men cross-sectionally and, for the first time, prospectively after 2 years of follow-up, with and without adjustment for potential confounders including serum creatinine. Design: Two hundred and seventy-two participants were randomly selected from the Cyprus Metabolism Study (1056 men, 18 years), of whom 93 subjects participated in the follow-up study 2 years after baseline assessment. Associations were also explored between total and free leptin levels (to serve as positive controls) and anthropometric metabolic variables. Results: In the cross-sectional study, lipocalin 2 levels were marginally correlated in the unadjusted model with central fat distribution but not with body weight or total body fat mass. After adjusting for age, smoking, activity, body mass index, fat percentage, waist-to-hip ratio, and serum creatinine, no correlation was found with any cardiovascular risk factor. There was no correlation with the homeostasis model assessment of IR (HOMA-IR) at baseline. In the prospective analyses, baseline levels of lipocalin 2 were not predictive of any variables in unadjusted or adjusted models. As expected, total and free leptin were associated with anthropometric and metabolic variables both cross-sectionally and prospectively. Conclusions: We demonstrate that lipocalin 2 is not an independent predictor of metabolic and cardiovascular risk factors in young men cross-sectionally or prospectively. [ABSTRACT FROM AUTHOR]