ALBERT

Description: Plasma consists of DNA released from multiple tissues within the body. Using genome-wide bisulfite sequencing of plasma DNA and deconvolution of the sequencing data with reference to methylation profiles of different tissues, we developed a general approach for studying the major tissue contributors to the circulating DNA pool. We tested this method in pregnant women, patients with hepatocellular carcinoma, and subjects following bone marrow and liver transplantation. In most subjects, white blood cells were the predominant contributors to the circulating DNA pool. The placental contributions in the plasma of pregnant women correlated with the proportional contributions as revealed by fetal-specific genetic markers. The graft-derived contributions to the plasma in the transplant recipients correlated with those determined using donor-specific genetic markers. Patients with hepatocellular carcinoma showed elevated plasma DNA contributions from the liver, which correlated with measurements made using tumor-associated copy number aberrations. In hepatocellular carcinoma patients and in pregnant women exhibiting copy number aberrations in plasma, comparison of methylation deconvolution results using genomic regions with different copy number status pinpointed the tissue type responsible for the aberrations. In a pregnant woman diagnosed as having follicular lymphoma during pregnancy, methylation deconvolution indicated a grossly elevated contribution from B cells into the plasma DNA pool and localized B cells as the origin of the copy number aberrations observed in plasma. This method may serve as a powerful tool for assessing a wide range of physiological and pathological conditions based on the identification of perturbed proportional contributions of different tissues into plasma.

Description: 44 years old lady presented with fever and pancytopenia in March 2014.CXR showed bilateral pneumonia. Hb 7.5xg/dl, plt 42x x109/l, wbc 1.2 x19neutrophils22%, lymphocytes75%.Circulating lymphocytes with hairy cytoplasmicprojections and indented nuclei were noted. Flow cytometry showed these abnormal lymphoid cells were CD19+ve, CD5-ve, CD 23-ve, FMC7+ve, CD25+ve, CD11c+ve and CD103+ve.Bone marrow biopsy revealed a hypercellular marrow with dense infiltration of lymphoid cells of the same immunophenotype. Braf V600 mutation was detected. Cladribine or pentostatin was out of stock and import of these drugs would take at least 2 months. In view of the severe pancytopenia and on -going infection, various treatment options were discussed with, the patient .Patient decided to start on vemurafenib 960mg twice daily while awaiting cladribine. After 8weeks of treatment, the peripheral blood counts were normalized. Hb 12.2g/dl, plt 153x x109/l, wbc 3.1x109/l, neutrophils 53%,lymphocytes 40%. Braf V600 mutation was no longer detected. Vemurafenib was well tolerated and the patient received treatment mainly as outpatient. Vemurafenib was discontinued after 8 weeks and the patient then received a 5-day course of cladribine. She remained in complete remission Discussion Vemurafenib had shown to be safe and effected in hairy cell leukemia patients who were refractory to or who relapsed after purine analogs.1,2 Still to be determined are the correct vemurafenib dosing strategy, the best timing , duration and scheduling of vemurafenib. Due to unusual circumstances, our patient received 8 weeks of vemurafenib as first line therapy. The patient achieved a complete remission with minimal residual disease. Follow data is needed to see how long the patient remains in remission 1. N Engl J Med 2014; 370:286-288 2. 19th Congress of the European Hematology Association (EHA): Abstract S696. Disclosures Off Label Use: Vemurafenib as first treatment of Hairy Cell Leukemia. Wong:johnson &johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Biogen-Idec: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer, MSD, Roche, BMS, Baxter, Amgen, Alexion: Research Funding.

Description: Multicentric Castleman’s disease (MCD) is a rare, lymphoproliferative disorder with high morbidity. MCD signs and symptoms are driven by dysregulated interleukin (IL)-6 production. Preliminary data suggest efficacy of siltuximab, a chimeric mAb against human IL-6, in MCD patients (van Rhee et al. J Clin Oncol 2010;28:3701-8). We evaluated the efficacy and safety of siltuximab in patients with symptomatic, measurable, HIV- and HHV-8-negative MCD in a phase 2, randomized, double-blind, controlled, multicenter study. Patients could be newly diagnosed/pre-treated and on stable, low-dose corticosteroids. Patients were randomly assigned 2:1 to siltuximab 11 mg/kg or placebo given by 1-h IV infusion q3w. All patients also received best supportive care to manage MCD symptoms. Patients received study agent until protocol-defined treatment failure, after which patients randomized to placebo could cross over to unblinded siltuximab. Primary analysis occurred after the last treated patient completed assessments at 48 wks. Primary endpoint was durable tumor and symptomatic response defined as PR or CR (Cheson criteria) by independent review and improvement/stabilization in MCD-related symptoms for ≥18 wks. Secondary endpoints included additional predefined efficacy measures and safety. 79 patients were randomized and treated with siltuximab (n=53) or placebo (n=26) from Feb 2010 to Feb 2013. Treatment arms were well balanced. Median age was 48 yrs, 48% were Asian, 39% were white, 66% were male, 30% were on corticosteroids, and 58% had prior systemic therapy. Patients had mixed (44%), hyaline vascular (33%), or plasmacytic (23%) histologic subtypes by pre-randomization central pathology review. Baseline MCD symptoms included fatigue (86%), malaise (61%), night sweats (52%), peripheral sensory neuropathy (38%), anorexia and pruritus (37% each). Median treatment duration was 375 vs. 152 d with siltuximab vs. placebo, with 64% vs. 27% completing 48 wks of treatment. A higher percentage of durable tumor and symptomatic response was observed with siltuximab compared with placebo (34% (1 CR, 17 PR) vs. 0%; p=0.0012). Investigator-reported response provided consistent conclusions. Median duration of tumor and symptomatic response in siltuximab-treated patients of 340 d indicates prolonged disease control. Tumor response rate by central radiology review was 38% vs. 4% (p=0.0022). Median time to treatment failure was not reached vs. 134 d (p=0.0084). Median time to next treatment was not reached vs. 280 d (p=0.0013). Durable symptomatic response rate was 57% vs. 19% (p=0.0018), including complete symptom resolution in 25% vs. 0% (p=0.0037). Hb improvement by ≥15 g/L at wk 13 was seen in 61% vs. 0% anemic patients (p=0.0002). Sustained decreases in CRP (a marker of IL-6 bioactivity), ESR, and fibrinogen, and increase in albumin were seen with siltuximab. 13 of 26 patients on placebo crossed over to siltuximab. The safety profile as defined by frequencies of treatment-emergent AEs was similar between siltuximab and placebo despite the 〉2x longer treatment duration with siltuximab: gr ≥3 AEs 47% vs. 54%, SAEs 23% vs. 19%, AEs leading to discontinuation 23% vs. 38% (mostly due to PD), AEs leading to treatment interruption 28% vs. 19%. Infusion reactions with siltuximab were infrequent (8%) and low grade, except for 1 anaphylactic reaction that led to treatment discontinuation. Gr ≥3 AEs frequently reported with siltuximab were fatigue (9%); night sweats (8%); and hyperkalemia, hyperuricemia, localized edema, hyperhidrosis, neutropenia, thrombocytopenia, hypertension, and weight increased (4% each). Gr ≥3 AEs reasonably related to siltuximab reported in 〉1 patient were neutropenia and thrombocytopenia (4% each). 3 (6%) patients had SAEs reasonably related to siltuximab. 2 (4%) patients in siltuximab died due to PD after treatment discontinuation. 4 (15%) noncrossover patients in placebo died (1 AE, 3 PD). This is the first randomized study in MCD. The efficacy of siltuximab in MCD patients was demonstrated by durable tumor and symptom response, and clinical benefit was confirmed by marked improvement of time to treatment failure, MCD-related symptoms, Hb levels, and sustained reduction in inflammatory markers. In conjunction with the tolerable safety profile in this population, this study provides compelling evidence that siltuximab should be considered a new treatment of choice for MCD patients. Disclosures: Wong: Roche: Research Funding; MSD: Research Funding; Johnson & Johnson: Research Funding; Bayer: Consultancy, Research Funding; Novartis: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Biogen-Idec: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Baxter: Research Funding; Amgen: Research Funding; Alexion: Honoraria. Casper:St. Jude Children's Hospital and Research Center: Membership on an entity’s Board of Directors or advisory committees; Hutchinson Cancer Research Institute--Uganda: Membership on an entity’s Board of Directors or advisory committees; Up-To-Date: Royalties Patents & Royalties; National Institutes of Health: Research Funding; Janssen Research & Development: Consultancy, Research Funding. Munshi:Janssen Research & Development: Membership on an entity’s Board of Directors or advisory committees. Fosså:Janssen Research & Development: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Simpson:Janssen Research & Development: Honoraria. Goh:Gilead Sciences, Inc: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity’s Board of Directors or advisory committees; Janssen Pharmaceuticals Inc: Research Funding; Novartis Pte Ltd: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Hospira, Inc: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Cavet:Janssen Research & Development: Research Funding. Bandekar:Janssen Research & Development: Employment; Johnson & Johnson: Equity Ownership. Rothman:Janssen Research & Development: Employment; Johnson & Johnson: Equity Ownership. Puchalski:Janssen Research & Development: Employment; Johnson & Johnson: Equity Ownership. Chaturvedi:Janssen Research & Development: Employment; Johnson & Johnson: Equity Ownership. van de Velde:Johnson & Johnson: Equity Ownership; Janssen Research & Development: Employment. Vermeulen:Janssen Research & Development: Employment; Johnson & Johnson: Equity Ownership. van Rhee:Janssen Research & Development: Research Funding.

Description: RUNX3/AML2 is a Runt domain transcription factor like RUNX1/AML1 and RUNX2/AML3. Regulated by 2 promoters P1 and P2, RUNX3 is frequently inactivated by P2 methylation in solid tumors. Growing evidence has suggested a role of this transcription factor in hematopoiesis. However, genetic alterations have not been reported in blood cancers. In this study on 73 acute myeloid leukemia (AML) patients (44 children and 29 adults), we first showed that high RUNX3 expression among childhood AML was associated with a shortened event-free survival, and RUNX3 was significantly underexpressed in the prognostically favorable subgroup of AML with the t(8;21) and inv(16) translocations. We further demonstrated that this RUNX3 repression was mediated not by P2 methylation, but RUNX1-ETO and CBFβ-MYH11, the fusion products of t(8;21) and inv(16), via a novel transcriptional mechanism that acts directly or indirectly in collaboration with RUNX1, on 2 conserved RUNX binding sites in the P1 promoter. In in vitro studies, ectopically expressed RUNX1-ETO and CBFβ-MYH11 also inhibited endogenous RUNX3 expression. Taken together, RUNX3 was the first transcriptional target found to be commonly repressed by the t(8;21) and inv(16) fusion proteins and might have an important role in core-binding factor AML.

Description: Background The Philadelphia chromosome−negative classical MPNs (myelofibrosis [MF], polycythemia vera [PV], and essential thrombocythemia [ET]) are associated with a pronounced symptom burden, including fatigue, night sweats, itching, and inactivity that may affect patients' HRQOL. There is a limited real-world evidence from many of the Asian countries, including Middle East, regarding the impact of MPNs on HRQOL, or the economic burden associated with these diseases. MERGE is a multinational, multicenter, nonintervention study conducted in adult patients with MPNs in Asia, including Middle East, Turkey, and Algeria. The present analysis evaluated the impact of MPNs on HRQOL of patients from MERGE and explored the association of HRQOL with the clinical outcomes and resource utilization. Method The MERGE registry included patients with MPN diagnosed as per the World Health Organization 2008 criteria. Patients were planned to be followed up for 2 years (5 visits over the course of study). MPN Symptom Assessment Form Total Symptom Score (MPNSAF TSS) was administered during the routine biannual follow-up visits to assess the HRQOL. MPNSAF TSS score was calculated only for patients who completed at least 6 of the 10 items on the MPNSAF TSS questionnaire. The level of inter-rater agreement between physicians and patients on the proportion of symptomatic patients was assessed through Cohen's Kappa coefficient. Further, an ANCOVA (Analysis of covariance) model was applied to estimate the influence of the baseline variables (age, sex, weight, height, family history of MPNs, comorbidities, time to initial MPNs diagnosis, type of MPN initial diagnosis, baseline hemoglobin and platelet count, Eastern Cooperative Oncology Group Performance Status [ECOG PS], and time since diagnosis to treatment initiation) on the TSS score. Variables with univariate P-value 〈 0.20 were included in the multivariate model. Furthermore, medical resource utilization was assessed by evaluating the inpatient and outpatient visits, hospice care, emergency room visits, and day care. Results Of the 884 eligible patients with MPNs, 169 had MF, 301 had PV, 373 had ET, and 41 had unclassified MPN. During the study, 64% of patients received hydroxyurea, 15% interferon, 15% JAK inhibitors, and 10% anagrelide either alone or in combination. At baseline, the proportion of patients presenting at least 1 of the symptoms was higher in the MF group (96.4%), compared to the total MPN patients (91.8%). In addition, the TSS (mean [SD]) at baseline was highest in the patients with MF (23.5 [17.47]) as compared to patients with ET (14.6 [14.26]) and PV (16.6 [14.84]). During the study duration and follow-up, the TSS remained approximately constant at subsequent visits. Physicians reported a lower proportion of symptomatic patients than the proportion self-reported by patients, although, there was better agreement between physicians and patients for pruritus and night sweats (Kappa, 0.61-0.80) (Table 1) than for other symptoms (Kappa, 0.41-0.60). Across MPN subtypes, inter-rater agreement was lowest for patients with MF compared to patients with ET or PV. In a multivariate adjusted mixed effect regression model, female gender, type of MPN (MF), presence of comorbidities, lower baseline hemoglobin were independently and positively associated with the symptom score values. Overall, 24.3% of the patients had at least 1 inpatient visit, with a mean duration of 11.1 days. Outpatient visits were the most commonly observed healthcare resource used (95.5%), without remarkable change during the follow-up period. Patients with ET had a lower mean number of inpatient visits (mean [SD]: 0.9 [0.77] days), and patients with MF had more outpatient visits (mean [SD]: 5.2 [3.17] visit) on an average, compared to the entire MPN group. Conclusion Despite being on treatment, patients with MPN in MERGE had substantial symptom burden, which did not change over the course of the study. A discordance between physician and patient perception of symptom assessment was seen in this study, indicating that in addition to spleen and hematological investigations, a more systematic assessment such as the use of MPNSAF TSS could help to better evaluate patients' symptoms and understand the disease and its treatment burden. Disclosures Taher: Celgene Corp.: Research Funding; Ionis Pharmaceuticals: Consultancy; Protagonist Therapeutics: Consultancy; La Jolla Pharmaceutical: Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Yassin:Novartis: Research Funding. Rippin:Employee of IQVIA - doing consultancy for Novartis: Consultancy. Sadek:Novartis Pharmaceutical Corporation: Employment. Siddiqui:Novartis Pharma AG: Employment, Equity Ownership. Wong:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Description: Background The Philadelphia chromosome−negative classical myeloproliferative neoplasms ([MPNs], including essential thrombocythemia [ET], polycythemia vera [PV], and myelofibrosis [MF]), are generally associated with a substantial disease burden, often leading to a reduced quality of life (QOL) and shortened survival in many patients (pts). There has been a lack of estimates for the incidence/prevalence and treatment patterns of MPNs in many regions of the world, including countries from South Asia, Asia Pacific, Middle East, and Turkey. Hence, there is a need to establish databases like registries, which would provide information on the "real-world" data in these regions. The MERGE registry was initiated with an objective to collect data on the epidemiological indices of MPNs and existing treatment patterns in Asia, including Middle East, Turkey, and Algeria. This primary descriptive analysis from the MERGE registry was performed to estimate the incidence/prevalence, natural disease course, and treatment patterns of MPNs in these countries. Methods MERGE is a multinational, multicenter, nonintervention study that included adult pts with MPNs, who were diagnosed according to World Health Organization 2008 criteria. The data were collected retrospectively (since diagnosis) and prospectively after enrollment in the study. Disease assessments were scheduled every 6 months up to 5 visits, with a minimum of 2 years of follow-up. Pts who participated or were participating in a randomized clinical trial were allowed. Data were analyzed descriptively. Results In total, 884 MPN pts (ET=373, PV=301, MF=169, and unclassified=41) were included in the full analysis data set. The median age was 58 years (range, 47-66 years; younger compared to other regions) and 50% pts were males. Baseline pt characteristics by MPN subtype are summarized in Table 1. About 57% of pts were diagnosed by incidental finding of abnormal blood results followed by bone marrow evaluation. In these countries, the prevalence and incidence of MPNs are estimated to be 57-81 and 12-15 per 100.000 hospital-patients per year over the last 4 years, respectively. As assessed by MPN Symptom Assessment Form (MPNSAF), 92% of the pts reported at least 1 symptom. At baseline, fatigue was the most common symptom in all 3 MPN subtypes (71% MPN; 78% MF; 71% ET; and 68% PV). Inactivity (64%), early satiety (61%), abdominal discomfort (57%), bone pain (56%), weight loss (52%), night sweats (46%), and fever (29%) were more common in MF; whereas, itching in PV pts (50%). MF pts had the highest total symptom score at baseline (mean [SD], 23.5 [17.47]) as compared to ET (mean [SD], 14.6 [14.26]) and PV pts (mean [SD], 16.6 [14.84]). Overall, 64% of pts had ECOG performance status of 0 and 26% had ECOG 1. During study period, the most common nonpharmacological intervention was red cell transfusion in MF and ET pts, and phlebotomy in PV pts. Splenectomy (n=2) and stem cell transplantation (n=4) were rarely employed (6 MF pts). Hydroxyurea (HU) was the most common first-line therapy in all 3 MPN subtypes (overall, 54%; PV, 61%; ET, 54%; and MF, 39%), followed by aspirin. Other common first-line therapies were anagrelide (10%) and interferon (9%) in ET pts, antineoplastic (6%) and clopidogrel (6%) in PV, and JAK2 inhibitors in MF pts (15%). More than 75% of the induction therapies were monotherapies, with less than 3% of pts receiving 3 or more drug combinations as primary treatment. Patients with MF often received monotherapy (81%), than the other patients with MPN. Median duration of first-line therapy was about 6 months (95% CI, 1-21 months), and first-line therapy discontinuation rates of 35%, 36%, and 30% were noted in ET, PV and MF pts, respectively. Interferon was used in 8% of in the second-line setting. JAK2 inhibitors were more frequently (14%-17%) used in the second-and third-line settings. Conclusions The prevalence and incidence of MPNs in countries from Asia Pacific were derived using the number of pts visiting the corresponding hospitals. Thus, the resulting incidence and prevalence reported here are not directly comparable with the country-based prevalence/incidence and may overestimate the actual values. At baseline, pts with MPNs had significant disease burden. The most common first-line therapy was HU, though discontinuation rates of first-line therapies were high, and JAK2 inhibitors were mostly used in the second-line/third-line settings. Disclosures Yassin: Novartis: Research Funding. Taher:La Jolla Pharmaceutical: Research Funding; Ionis Pharmaceuticals: Consultancy; Celgene Corp.: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Protagonist Therapeutics: Consultancy. Kim:Novartis Korea: Honoraria. Rippin:Employee of IQVIA - doing consultancy for Novartis: Consultancy. Sadek:Novartis Pharmaceutical Corporation: Employment. Siddiqui:Novartis Pharma AG: Employment, Equity Ownership. Wong:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Description: Secreted-frizzled related proteins (SFRPs) are modulators of the Wnt signaling pathway that is closely involved in normal and malignant hematopoiesis. Epigenetic deregulation of Wnt modulators leading to aberrant signaling has been reported in adult patients with acute myeloid leukemia (AML), but its occurrence in childhood patients with AML and the role of individual modulators are unclear. In this study, we examined SFRP1, SFRP2, SFRP4, and SFRP5 promoter methylation in 83 patients with AML (59 children and 24 adults) and found preferential SFRP1 methylation and mRNA down-regulation in the prognostically favorable subgroup of AML with t(8;21) translocation. Among the 4 genes, SFRP1 methylation independently predicted prolonged event-free and relapse-free survivals in childhood patients with nonacute promyelocytic leukemia with nonadverse cytogenetics. Mechanistically, we further demonstrated that RUNX1-ETO, the t(8;21) fusion product, specifically bound the SFRP1 promoter and repressed its transcription via a consensus RUNX binding site. In t(8;21)–leukemia cells, SFRP1 selectively inhibited canonical Wnt signaling and cellular proliferation that were associated with concomitant down-regulation of Wnt/β-catenin target genes, including CCND1 and MYC. Taken together, we identified SFRP1 as a transcriptional repression target of the t(8;21) fusion protein and demonstrated a novel mechanism of Wnt activation in a specific subtype of AML.

Description: Background: ITP is an acquired autoimmune disorder. Second-line treatment options include EPAG, romiplostim (both stimulate platelet production), ritux (a monoclonal anti-CD20 antibody that causes temporary but complete depletion of peripheral B cells), splenectomy (spl), and other immunosuppressive agents. This subanalysis of EXTEND, a global, open-label, extension study, evaluated long-term EPAG in adults with ITP of ≥6 months' duration according to prior ritux use. Aims: Describe efficacy and safety of EPAG in ITP patients (pts) according to prior ritux use. Methods : In EXTEND (Wong et al. Blood 2017;130:2527-36), pts started EPAG at 50 mg/day, with dose adjusted as required to achieve platelet counts of 50-200x109/L. Results: Of 302 pts in EXTEND, 70 (23%) had previously received ritux. Of these pts, mean±SD age was 53±14 years (yrs), median (range) time since diagnosis was 71.3 (12-362) months, 67% were splenectomized, 61% were female, 76% had baseline platelet counts

Description: Key Points An international panel established the first ever diagnostic criteria for iMCD based on review of 244 clinical cases and 88 tissue samples. The criteria require multicentric lymphadenopathy with defined histopathology, ≥2 clinical/laboratory changes, and exclusion of iMCD mimics.

Description: INTRODUCTION Siltuximab (SylvantTM), a monoclonal antibody against interleukin-6, was recently approved in both US and EU for treatment of adult patients with Multicentric Castleman's Disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative. Information on MCD symptoms, functioning and well-being was gathered in a pivotal global registration study (MCD2001, Van Rhee 2014) with a general patient reported outcome (PRO) questionnaire: the Short Form-36 (SF-36, acute version 2), and other PRO measures. OBJECTIVES Evaluate the longitudinal impact of siltuximab on symptoms, functioning and well-being as measured by SF-36 when compared to placebo. METHODS MCD2001 was a randomized (2:1), double-blind, placebo-controlled, multicenter study to determine the safety and efficacy of siltuximab in patients with symptomatic MCD. Patients received siltuximab 11 mg/kg or placebo by intravenous infusion every 3 weeks in combination with best supportive care (BSC). Subjects (N = 79) completed the SF-36 at baseline and every three weeks throughout the treatment period; 1998 scoring weights were applied. Patients, whose baseline SF-36 domain scores were below the general population norm for their age group (n = 46) were included in an analysis to compare by treatment arm the proportion of patients achieving an SF-36 domain score equal to, or greater than, the population norm at final visit. This analysis, hereafter referred to as a return to general population health norms (RTN), was conducted separately for each SF-36 domain. It is regarded as clinically-relevant improvement (CRI) since disease control is the current treatment goal. Referent norms were based on the US general population SF-36 cohort from the Medical Outcomes Study (Ware et al 1998). An intent-to-treat analysis was applied where missing data were not imputed; data were censored at treatment discontinuation, including crossover. Odds ratio was calculated between the two treatment arms and statistically compared with the Fisher’s Exact test. RESULTS At baseline the population demonstrated inferior health compared to general population across all SF-36 domains (Figure 1). The odds of siltuximab-treated patients for reaching RTN vs. placebo patients in the Vitality, Role-emotional and Social functioning domains are significant, with odds ratios of 5.3 (p=0.049), 5.5 (p=0.011) and 11.4 (p=0.014), respectively. A positive health trend was observed for patients who received siltuximab compared with placebo across all other domains, particularly Role-physical (5.5, p=0.067; Figure 2). Sensitivity analysis using a literature-based CRI supported the robustness of the results. CONCLUSION Overall MCD patients reported notably inferior health compared to the general population at baseline; siltuximab significantly improved the odds for RTN versus placebo in the Role-emotional, Vitality and Social function domains, as well as demonstrated a trend to improve health across all other SF-36 domains among MCD patients who were below the norms at baseline. A clinically-relevant PRO benefit for physical and mental health was observed with siltuximab therapy, as measured with the SF-36, which supports the “disease control” treatment goal. References Van Rhee et al. Siltuximab for multicentric Castleman’s disease:a randomised, double-blind, placebo-controlled trial, Lancet Oncol, 2014, 15(9):966-74 Teschendorf B et al. Development and Content Validation of a Multicentric Castleman’s Disease Symptom Scale; Value in Health, 2010, 13(7): A470 Ware et al. SF-36v2 health survey: manual and interpretation guide. 1998 Disclosures van Rhee: Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees. Casper:Janssen: Consultancy, Research Funding. Robinson:Johnson & Johnson: Employment, Stocks Other. He:Janssen: Employment, Equity Ownership. Vermeulen:Janssen Biologics: Employment, Equity Ownership, Honoraria. van de Velde:Janssen Research & Development: Employment, Equity Ownership. Wong:Johnson & Johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Research Funding; Biogen-Idec: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.