10008 Background: MM pts with LMD have a dismal prognosis, with a median overall survival (OS) < 3 months and no approved therapies. IT administration of interleukin-2 (IL2) achieves survival in ~15% of MM LMD pts, but at cost of severe toxicities. Given the favorable clinical activity and safety of systemic anti-PD1, we hypothesized that IT N administration is safe and can achieve clinical benefit in pts with LMD. Methods: The primary objectives of this first-in-human study (NCT03025256) were to determine the safety and the maximum tolerated dose (MTD) of IT N given with IV N in MM pts with LMD. Eligible pts had MM, ECOG PS < / = 2, and evidence of LMD by MRI and/or CSF cytology. Dexamethasone < / = 4mg/daily was allowed. For cycle 1, IT N is administered via intraventricular reservoir on day (D) 1; Blood and CSF is collected at multiple time points for translational research. For subsequent cycles (every 14 days), pts receive IT N on D1, followed by IV N 240 mg on D2. IT N doses evaluated were 5, 10, and 20 mg. Bayesian mTPI methodology was used to define the MTD. The study was recently amended to allow for concurrent BRAF/MEK inhibitor(i) treatment. Results: To date, 15 pts have been treated: two at 5, three at 10, and 10 at 20 mg IT N. Median age at LMD diagnosis was 41.8 (30.9-73.2) years; 6 pts are male. All pts had radiographic evidence of LMD and neurological symptoms; 8 pts had positive CSF cytology. 12 pts received prior therapies for their MM: anti-PD1 (n = 11), BRAFi/MEKi (n = 9), chemo (n = 2), IT IL2 (n = 4) other (n = 2). 11 pts had prior XRT, including whole brain RT (n = 7). 1 pt was treatment-naïve. The median numbers of IT N doses was 4 (1-42). No grade (Gr) 4-5 AEs were attributed to IT N or IV N; only 4 events (Gr 1, n = 2; Gr2, n = 2) were possibly related to the IT N. With a median follow-up of 18.7 weeks (1-83.3 wks), the median OS is 46.1 weeks (0.1-83.3). Clinical response data, translational research endpoints, including changes in CSF cytokines and cfDNA, will be reported. Conclusions: The trial demonstrates the feasibility of prospective clinical trials in MM patients with LMD. The combination of IT/ IV N was safe and well-tolerated, with no unexpected systemic or neurological toxicity. Final presentation will include results of LMD composite response assessment, comparative analysis of longitudinal CSF/blood samples to assess immunologic effects. Finally, the interim OS of the patients is encouraging, and supports further evaluation of IT administration of immunotherapy agents for pts with MM and LMD. Clinical trial information: NCT03025256.
Background: A recently discovered occult HCV entity reported by various investigators seems to be highly controversial. Especially, the clinical significance of these findings remains uncertain. For optimal outcome of antiviral therapy, investigation of occult HCV needs a broad-based probe in order to investigate the results of viral therapy and its host/viral interaction. The current study was aimed at determining the prevalence of occult HCV in peripheral blood lymphocytes of predominantly genotype 3 HCV-infected patients after completion of antiviral therapy and to investigate long term outcomes in the presence or absence of PBMC positivity. Method: A total of 151 chronic, antiHCV and serum RNA-positive patients were enrolled in the study. Patients with a complete virological response at the end of treatment were screened for the presence of viral RNA in their PBMCs and were followed for up to one year for the presence of serum and PBMC viral genomic RNA.
BACKGROUND: Melanoma patients with LMD have a median survival of 1.8 months; there is significant medical need for innovative therapeutic strategies. METHODS: Stage IV melanoma patients were diagnosed with LMD by positive CSF cytology and/or leptomeningeal enhancement on post-contrast MRI. Patients received treatment with 1-5 doses/week of intrathecal IL-2 (IT IL2) for 4 weeks, followed by weekly injections for 4
There is a critical need for effective treatments for leptomeningeal disease (LMD). Here, we report the interim analysis results of an ongoing single-arm, first-in-human phase 1/1b study of concurrent intrathecal (IT) and intravenous (IV) nivolumab in patients with melanoma and LMD. The primary endpoints are determination of safety and the recommended IT nivolumab dose. The secondary endpoint is overall survival (OS). Patients are treated with IT nivolumab alone in cycle 1 and IV nivolumab is included in subsequent cycles. We treated 25 patients with metastatic melanoma using 5, 10, 20 and 50 mg of IT nivolumab. There were no dose-limiting toxicities at any dose level. The recommended IT dose of nivolumab is 50 mg (with IV nivolumab 240 mg) every 2 weeks. Median OS was 4.9 months, with 44% and 26% OS rates at 26 and 52 weeks, respectively. These initial results suggest that concurrent IT and IV nivolumab is safe and feasible with potential efficacy in patients with melanoma LMD, including in patients who had previously received anti-PD1 therapy. Accrual to the study continues, including in patients with lung cancer. ClinicalTrials.gov registration: NCT03025256.
Portal hypertension and liver cirrhosis may predispose patients to varices, which have a propensity to bleed and cause significant morbidity and mortality. These varices are most commonly located in the gastroesophageal area; however, rarely ectopic varices may develop in unusual locations outside of this region. Haemorrhage from these sites can be massive and difficult to control; thus early detection and management may be lifesaving. We present a case of occult gastrointestinal bleeding in a patient with underlying alcoholic liver disease where an ectopic varix was ultimately detected with push enteroscopy.
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