Chart review study of real-world clinical outcomes in patients with cutaneous T-cell lymphoma treated with extracorporeal photopheresis in the US in 2017-2019.

BACKGROUND: Response rates of approved systemic therapies for cutaneous T-cell lymphoma (CTCL) hover near 30%, suggesting unmet need. This study describes real-world treatment patterns and response rates of extracorporeal photopheresis (ECP) in CTCL patients. METHODS: A chart review was conducted in the United States of adults with CTCL who initiated ECP between January 1, 2017, and February 28, 2019, and received at least three months of ECP treatment as monotherapy or concomitant therapy. Clinical outcomes were collected quarterly for up to 18 months. RESULTS: The 52 patients were predominantly Caucasian. Half were male; median age was 69 years. Most patients had Sézary syndrome (50%) or mycosis fungoides (36.5%). Nearly 40% of patients had stage IV disease; 33% had lymph node involvement. Nineteen patients (36.5%) achieved response (>50% reduction in BSA affected); median time to response was 6.5 months. The percentage of patients rated as at least minimally improved was 59.5% at 6 months (N = 22), 75.0% at 9 months (N = 24), and 60.0% at 12 months (N = 15) after ECP initiation. CONCLUSIONS: Despite the ECP treated population in this study being older and having more advanced-stage disease than recent trials, response rates were comparable. These real-world findings support ECP as an effective treatment option for CTCL patients.

Association of plasma endotoxin, inflammatory cytokines and risk of colorectal adenomas.

BACKGROUND: Recent studies suggest that bacterial endotoxins may be associated with various chronic diseases, including colorectal adenomas and cancer. Given the evidence linking inflammation and colorectal cancer, we sought to determine if plasma endotoxin concentrations are associated with indicators of systemic or local inflammation and colorectal adenomas. METHODS: This cross-sectional study consisted of participants who underwent screening colonoscopies and included adenoma cases (n=138) and non-adenoma controls (n=324). Plasma concentrations of endotoxin were measured with Limulus Amebocyte Lysate (LAL) assay. We quantified concentrations of inflammatory cytokines, interleukin-4 (IL-4), IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha (TNF-α), and interferon-γ (IFN-γ) in plasma by ELISA and mRNA expression levels in rectal mucosal biopsies by quantitative RT-PCR. Interleukin-17 was evaluated only in the rectal mucosa. RESULTS: Compared to subjects with low plasma endotoxin concentrations, those with higher concentrations were more likely to have adenomas (OR 1.4, 95% CI 1.0-2.1). Among subjects with adenomas, those with villous histology were more likely to have higher endotoxin concentrations (5.4 vs. 4.1EU/mL, p=0.05) and lower plasma IFN-γ (0 vs. 1.64 pg/mL, p=0.02) compared to those with only tubular adenomas. Cases showed a trend of having higher plasma TNF-α levels than controls (p=0.06), but none of the other plasma or rectal mucosal cytokine levels differed between cases and controls. Elevated mucosal IL-12 levels were associated with having multiple adenomas (p=0.04). Higher concentrations of plasma endotoxin predicted increased plasma IL-12 levels (OR 1.5, 95% CI 1.0-2.2) and rectal mucosal IL-12 (OR 1.9, 95% CI 1.0-3.7) and IL-17 gene expression (OR 2.2, 95% CI 1.0-4.6). CONCLUSIONS: These findings suggest that interactions between elevated plasma endotoxin concentrations and inflammatory cytokines may be relevant to the development of colorectal adenomas.