Citations

7000 Background: MMB, an oral JAKi, has been shown in early trials to reduce spleen volume, improve disease associated symptoms (Sx) and improve RBC transfusion (Tx) requirements in patients (pts) with MF. This study was designed to test non-inferiority of MMB vs RUX in splenic volume reduction and Sx amelioration, and superiority in Tx requirement, in JAKi naïve MF pts. Methods: Eligibility: MF, IPSS high risk, Int-2, or symptomatic Int-1; palpable spleen ≥5cm; platelets ≥ 50 K/μl, and no Gr ≥2 peripheral neuropathy (PN). Stratification by Tx dependency and platelets (<100, 100-200 and >200 K/μl). Pts were randomized 1:1 to 24 wks of MMB 200 mg qd + RUX placebo or RUX 20 mg bid (or modified per label) + MMB placebo, after which all pts could receive open label MMB. Assessments: spleen volume by MRI, and pt reported Sx using a daily eDiary of modified MPN-SAF Total Sx Score (TSS). Primary endpoint was splenic response rate (SRR; ≥35% reduction in volume from baseline) at 24 wks. Secondary endpoints, evaluated sequentially at 24 wks, were rates of TSS response (≥50% reduction from baseline), RBC Tx independence (TI), RBC Tx dependence (TD) and of RBC Tx . Results: 175 of 215 (81%) and 201 of 217 (93%) pts randomized to MMB and RUX, respectively, completed the 24 wk DB phase. Efficacy results are shown in Table. Most common Gr ≥3 AEs in the DB phase with MMB were thrombocytopenia (7%) and anemia (6%), and with RUX were anemia (23%), thrombocytopenia (5%) and neutropenia (5%). Gr ≥3 infections occurred in 7% of MMB and 3% of RUX pts. Treatment emergent PN occurred in 22 (10%) of MMB (all Gr ≤2) and 10 (5%) of RUX (9 Gr ≤2, 1 Gr 3) pts in DB phase, none discontinuing study drug for PN. Overall, AEs led to study drug D/C in 13% of MMB and 6% of RUX pts in DB phase. Conclusions: In pts with JAKi naive MF, 24 weeks of MMB is non-inferior to RUX for spleen response but not for symptom response. MMB treatment is associated with a reduced transfusion requirement. NCT01969838. [Table: see text]

e15641 Background: CC pts with biliary stents or catheters are prone to have obstruction/infection and studies show 20-40% present with fever/or jaundice requiring urgent treatment for which there is no uniform guideline. We aimed to develop an expert panel consensus on this topic using the modified RAND/UCLA Delphi process to rate treatment appropriateness. Methods: We recruited 13 physician experts from relevant specialty, geography, and practice settings. Patient scenarios were developed and panelists rated the therapies before and after a face-to-face discussion. The appropriateness of various therapies was rated on a 1-9 scale and classified as appropriate, inappropriate, or uncertain. Scenarios with > 2 ratings of 1-3 (inappropriate) and > 2 ratings of 7-9 (appropriate) were considered to have disagreement and were not assigned an appropriateness rating. Results: Panelists were from all US regions (92%) and the UK (8%); had practiced for a mean 16.5 years (4-33 years). Panelists rated 480 scenarios before the meeting, but re-rated only 288 clinical scenarios as they felt that ongoing treatment with chemotherapy did not influence decision-making. Disagreement decreased from 37.5% before the meeting to 10.4% after. Consensus statements are summarized in the table below. Conclusions: The Delphi process produced consensus guidelines to fill an unmet need in urgent management of ascending cholangitis in pts with CC. (Support: The Cholangiocarcinoma Foundation). [Table: see text]

Abstract Castleman disease (CD) describes a group of heterogeneous hematologic disorders with characteristic histopathological features. CD can present with unicentric or multicentric (MCD) regions of lymph node enlargement. Some cases of MCD are caused by human herpesvirus-8 (HHV-8), whereas others are HHV-8–negative/idiopathic (iMCD). Treatment of iMCD is challenging, and outcomes can be poor because no uniform treatment guidelines exist, few systematic studies have been conducted, and no agreed upon response criteria have been described. The purpose of this paper is to establish consensus, evidence-based treatment guidelines based on the severity of iMCD to improve outcomes. An international Working Group of 42 experts from 10 countries was convened by the Castleman Disease Collaborative Network to establish consensus guidelines for the management of iMCD based on published literature, review of treatment effectiveness for 344 cases, and expert opinion. The anti–interleukin-6 monoclonal antibody siltuximab (or tocilizumab, if siltuximab is not available) with or without corticosteroids is the preferred first-line therapy for iMCD. In the most severe cases, adjuvant combination chemotherapy is recommended. Additional agents are recommended, tailored by disease severity, as second- and third-line therapies for treatment failures. Response criteria were formulated to facilitate the evaluation of treatment failure or success. These guidelines should help treating physicians to stratify patients based on disease severity in order to select the best available therapeutic option. An international registry for patients with CD (ACCELERATE, #NCT02817997) was established in October 2016 to collect patient outcomes to increase the evidence base for selection of therapies in the future.

Abstract Background Prior work has shown that urinary soluble CD163 (usCD163) displays excellent biomarker characteristics for detection of active renal vasculitis using samples that included new diagnoses with highly active renal disease. This study focused on the use of usCD163 in the detection of the more clinically relevant state of mild renal flare and compared results of usCD163 testing directly to testing of urinary monocyte chemoattractant protein-1 (uMCP-1). Methods Patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV, n = 88) were identified within a serially sampled, longitudinal and multicentre cohort. Creatinine-normalized usCD163 and uMCP-1 levels were measured by enzyme-linked immunosorbent assay and, both alone and in combination, were compared between times of active renal AAV and during remission and/or active non-renal AAV. Results Samples from 320 study visits included times of active renal vasculitis (n = 39), remission (n = 233) and active extrarenal vasculitis (n = 48). Median creatinine levels were 0.9 mg/dL [interquartile range (IQR) 0.8–1.2] in remission and 1.4 mg/dL (IQR 1.0–1.8) during renal flare. usCD163 levels were higher in patients with active renal vasculitis compared with patients in remission and those with active extrarenal vasculitis, with median values of 162 ng/mmol (IQR 79–337), 44 (17–104) and 38 (7–76), respectively (P &lt; 0.001). uMCP-1 levels were also higher in patients with active renal vasculitis compared with patients in remission and those with active extrarenal vasculitis, with median values of 10.6 pg/mmol (IQR 4.6–23.5), 4.1 (2.5–8.4) and 4.1 (1.9–6.8), respectively (P &lt; 0.001). The proposed diagnostic cut-points for usCD163 and uMCP-1 were 72.9 ng/mmol and 10.0 pg/mmol, respectively. usCD163 and uMCP-1 levels were marginally correlated (r2 = 0.11, P &lt; 0.001). Combining novel and existing biomarkers using recursive tree partitioning indicated that elevated usCD163 plus either elevated uMCP-1 or new/worse proteinuria improved the positive likelihood ratio (PLR) of active renal vasculitis to 19.2. Conclusion A combination of usCD163 and uMCP-1 measurements appears to be useful in identifying the diagnosis of subtle renal vasculitis flare.