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Objective The efficacy and safety of bortezomib-based therapy for relapsed/refractory multiple myeloma (RRMM) in clinical trials may differ from the oncology practice experience. The electronic VELCADE® OBservational Study was designed to prospectively evaluate bortezomib for multiple myeloma (MM) in real-world medical practice. Method Patients scheduled to receive intravenous bortezomib for MM were eligible. The primary objective was to evaluate clinical outcomes, including response, time to response, time to next therapy, treatment-free interval, progression-free survival (PFS), and overall survival (OS). Secondary objectives included safety and healthcare resource utilization. Results In total, 873 patients with a median of two therapy lines prior to initiating bortezomib were included. The overall response rate (≥partial response) was 69%, including 37% complete response/near-complete response. Median time to response was 1.8 months, median time to next therapy was 9.7 months, and median treatment-free interval was 7.9 months. After 22.6 months' median follow-up, median PFS was 12.0 months and median OS was 36.1 months. The most common adverse events (AEs) were neuropathy not otherwise specified (19%), diarrhea NOS, and thrombocytopenia (each 17%); 230 (26%) patients discontinued bortezomib due to AEs. Of 689 (79%) patients without baseline peripheral neuropathy (PN), the rate of new-onset any-grade PN increased to 51% (12% grade 3/4) by cycle 8. Overall, 244 (28%) patients were hospitalized, 372 (43%) attended an outpatient visit, and 341 (39%) underwent a diagnostic/therapeutic procedure during bortezomib treatment. Conclusion These prospective real-world data demonstrate the effectiveness and safety of bortezomib-based therapy for RRMM and confirm high response rates and long OS for this population.

Erythropoiesis-stimulating agents are first choice for treating anemia in low-risk MDS. This double-blind, placebo-controlled study assessed the efficacy and safety of epoetin-α in IPSS low- or intermediate-1 risk (i.e., low-risk) MDS patients with Hb ≤ 10.0 g/dL, with no or moderate RBC transfusion dependence (≤4 RBC units/8 weeks). Patients were randomized, 2:1, to receive epoetin-α 450 IU/kg/week or placebo for 24 weeks, followed by treatment extension in responders. The primary endpoint was erythroid response (ER) through Week 24. Dose adjustments were driven by weekly Hb-levels and included increases, and dose reductions/discontinuation if Hb > 12 g/dL. An independent Response Review Committee (RRC) blindly reviewed all responses, applying IWG-2006 criteria but also considering dose adjustments, drug interruptions and longer periods of observation. A total of 130 patients were randomized (85 to epoetin-α and 45 to placebo). The ER by IWG-2006 criteria was 31.8% for epoetin-α vs 4.4% for placebo (p

The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18-65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR) = 0.76, 95% confidence interval (95% CI) of 0.65-0.89, P = 0.001). Overall survival (OS) was similar in the PAD versus VAD arm (HR = 0.89, 95% CI: 0.74-1.08, P = 0.24). The incidence of SPM were similar between the two arms (7% each, P = 0.73). The negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone size >= 10%) and renal impairment at baseline (serum creatinine > 2 mg dl(-1)) on PFS and OS remained abrogated in the PAD but not VAD arm. OS from first relapse/progression was similar between the study arms (HR = 1.02, P = 0.85). In conclusion, the survival benefit with BTZ induction/maintenance compared with classical cytotoxic agents and thalidomide maintenance is maintained without an increased risk of SPM.

Introduction: The introduction of new treatments over the past 2 decades has improved survival outcomes in patients with multiple myeloma (MM), yet MM remains incurable. Despite therapeutic advances, most patients with MM eventually relapse and/or become refractory to treatment, and cycle through standard drug classes of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies (mAbs), becoming triple-class exposed. These triple-class exposed patients represent a population with an urgent unmet clinical need and are a major focus for the development of new therapies. There are currently no prospective data outside of clinical trials on standard-of-care (SOC) in MM patients who progress after these treatment regimens. LocoMMotion (NCT04035226) is the first prospective study to assess the efficacy and safety of real-life SOC treatments in triple-class exposed patients with relapsed/refractory MM (RRMM). Initial analysis at a median follow-up of 3.7 months (range: 0.0-12.7) showed an overall response rate (ORR) of 20.1% (95% CI: 15.0-26.0), with only 5% of patients achieving very good partial response or better. Here, we report updated results from LocoMMotion with a longer median duration of follow-up (7.8 months), along with progression-free survival (PFS) and overall survival (OS) data. Methods: LocoMMotion is a non-interventional study of 246 patients across 10 countries (the US and 9 in Europe) and 75 sites. Patients (aged ≥18 years) with a documented diagnosis of MM were included if they received ≥3 prior lines of therapy or were double-refractory to a PI and IMiD; had measurable disease at screening; received at least a PI, an IMiD, and anti-CD38 mAb with documented progressive disease since their last line of therapy; and had an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1. Patient-level data and the most common SOC treatments were collected and analyzed during the study period (August 2019 through October 2020). Real-life SOC treatments were defined as those used in local clinical practice. Responses were assessed per International Myeloma Working Group response criteria. A review committee assessed the ORR (primary objective) of real-life current SOC as well as disease progression for the determination of PFS. Secondary objectives included evaluation of additional efficacy endpoints, including OS, and safety. Results: As of the data cut-off date of March 9, 2021, 246 patients were included with a median follow-up of 7.8 months (range: 0.1-16.9); 23 (9.3%) patients were from the US and 223 (90.7%) were from Europe. Median age was 68 years (range: 41-89), 133 (54.1%) were male, 180 (73.8%) had a baseline ECOG PS score of 1, and median time since initial MM diagnosis was 6.3 years (range: Conclusions: Updated results of this first, prospective study of real-life SOC treatment in triple-class exposed patients with RRMM confirm rapid disease progression after application of salvage therapy and poor outcomes with currently available treatments. New treatment approaches with novel therapies are needed to improve outcomes in this patient population. Disclosures Moreau: Oncopeptides: Honoraria; Amgen: Honoraria; Abbvie: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Celgene BMS: Honoraria. Weisel: Roche: Honoraria; Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy; Novartis: Honoraria; Pfizer: Honoraria. Goldschmidt: Incyte: Research Funding; BMS: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Celgene: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Chugai: Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; GSK: Honoraria; Amgen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Janssen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Johns Hopkins University: Other: Grant; Molecular Partners: Research Funding; MSD: Research Funding; Mundipharma: Research Funding; Novartis: Honoraria, Research Funding; Dietmar-Hopp-Foundation: Other: Grant; Sanofi: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Takeda: Consultancy, Research Funding; Adaptive Biotechnology: Consultancy. Delforge: Amgen, Celgene, Janssen, Sanofi: Honoraria, Research Funding. Mohty: Novartis: Honoraria; Astellas: Honoraria; Gilead: Honoraria; Bristol Myers Squibb: Honoraria; Pfizer: Honoraria; Adaptive Biotechnologies: Honoraria; Sanofi: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Takeda: Honoraria; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Janssen: Honoraria, Research Funding. Cavo: Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Accommodations, Speakers Bureau; Adaptive Biotechnologies: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol-Myers Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Vij: BMS: Research Funding; Takeda: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; BMS: Honoraria; GSK: Honoraria; Oncopeptides: Honoraria; Karyopharm: Honoraria; CareDx: Honoraria; Legend: Honoraria; Biegene: Honoraria; Adaptive: Honoraria; Harpoon: Honoraria. Dytfeld: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Cilag: Consultancy, Current Employment, Honoraria, Membership on an entity's Board of Directors or advisory committees. Angelucci: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene BSM: Honoraria, Other: DMC; Blue Bird Bio: Honoraria, Membership on an entity's Board of Directors or advisory committees; Menarini-Stemline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: steering commitee, Speakers Bureau; Vertex Pharmaceuticals: Honoraria, Other: DMC; Crispr therapeutics: Honoraria, Other: DMC; Glaxo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. Perrot: GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; Sanofi: Honoraria, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Benjamin: Servier: Honoraria, Research Funding; Allogene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Gileai: Honoraria, Research Funding. Van de Donk: BMS/Celgene: Consultancy, Honoraria; Janssen: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Cellectis: Research Funding; Takeda: Consultancy; Roche: Consultancy; Novartis /bayer/servier: Consultancy. Ocio: MSD: Honoraria; Amgen: Consultancy, Honoraria; Bristol-Myers Squibb/Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria; Karyopharm: Consultancy; Oncopeptides: Consultancy, Honoraria; Pfizer: Consultancy; Secura-Bio: Consultancy. Scheid: Roche: Consultancy; Abbvie: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Gay: Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria. Rodriguez-Otero: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Clínica Universidad de Navarra: Current Employment; Celgene-BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Regeneron: Honoraria. Broyl: Celgene: Honoraria; Janssen Pharmaceuticals: Honoraria; Sanofi: Honoraria; Bristol-Meyer Squibb: Honoraria; Amgen: Honoraria. Potamianou: Janssen: Current Employment, Current holder of stock options in a privately-held company. Sakabedoyan: Janssen: Current Employment. Semerjian: Janssen: Current Employment. Keim: Janssen Research & Development: Current Employment. Strulev: Janssen Pharmaceutica NV: Current Employment. Schecter: Janssen: Current Employment, Current holder of stock options in a privately-held company. Vogel: Janssen Global Services, LLC: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Divested equity in a private or publicly-traded company in the past 24 months. Wapenaar: Janssen: Current Employment; Johnson & Johnson: Current holder of individual stocks in a privately-held company. Nesheiwat: Legend Biotech USA: Current Employment. San-Miguel: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Karyopharm, Merck Sharpe & Dohme, Novartis, Regeneron, Roche, Sanofi, SecuraBio, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sonneveld: SkylineDx: Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene/BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding. Einsele: Janssen, Celgene/BMS, Amgen, GSK, Sanofi: Consultancy, Honoraria, Research Funding. Mateos: Oncopeptides: Honoraria; GSK: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bluebird bio: Honoraria; Celgene - Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sea-Gen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Objectives This randomized, international, multicenter, open-label phase III study investigated the effects of experimental retreatment with subcutaneous bortezomib plus dexamethasone (VD) followed by prolonged bortezomib therapy vs. standard VD retreatment in patients with relapsed/refractory multiple myeloma. Methods Patients were randomized (2:1) to receive either experimental (n = 53) or standard (n = 27) retreatment, stratified by the number of prior therapy lines. Results The study was terminated prematurely with insufficient enrollment to adequately compare the retreatment therapies; results should be considered descriptive. After a median follow-up of 21.2 and 20.0 months in the experimental and standard arms, respectively, the median progression-free survival (primary endpoint) was 7.2 months (95% confidence interval 5.7–9.0) vs. 7.8 months (4.9–11.7). The overall response rate was 66% and 52% for experimental and standard retreatment regimens, respectively. Thrombocytopenia was the most common and most differentially observed grade ≥3 adverse event (experimental: 9% vs. standard: 22%). Any-grade peripheral neuropathies (including peripheral sensory neuropathies) were reported in 23% vs. 37% of patients. Conclusions This study showed no significant benefit with experimental vs. standard VD retreatment therapy. Further investigations are required to determine whether the experimental retreatment regimen is a suitable alternative to the current standard retreatment regimen. Trial registration: ClinicalTrials. gov identifier NCT01910987; MMY3033 This article is protected by copyright. All rights reserved.

8041 Background: Multiple myeloma (MM) remains incurable despite advances in medical treatment that have improved survival. Even with these improvements, most patients with MM eventually progress through standard drug classes of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), anti-CD38 monoclonal antibodies (mAbs), and others. There are currently no prospective data on real-world standard-of-care (SOC) in patients who progress after PIs, IMiDs, and anti-CD38 mAbs. Here, we present interim results from LocoMMotion (NCT04035226), the first prospective efficacy and safety study of real-life SOC in patients with RRMM. Methods: Eligible patients (aged ≥18 years [y]) with a diagnosis of MM were enrolled between August 2019 and October 2020 from 75 sites across 9 European countries and the US. Patients were included if they received ≥3 prior lines of therapy or were double-refractory to a PI and IMiD, had measurable disease at screening, received at least a PI, an IMiD, and anti-CD38 mAb with documented progressive disease since their last line of therapy, and had an ECOG PS score of 0 or 1. Responses were assessed per International Myeloma Working Group response criteria. A Response Review Committee assessed the overall response rate (ORR, primary objective) of real-life current SOC. Secondary objectives of the study included additional efficacy and safety evaluation of real-life SOC. Results: The data cut-off was November 4, 2020 for the first interim analysis of 225 patients with a median follow-up of 3.7 months (range: 0–12.7), 22 (9.8%) patients were from the US and 203 (90.2%) were from Europe. Median age was 68 y (range: 41–89), 124 (55.1%) were male, 162 (72.0%) had a baseline ECOG PS score of 1, and median time since initial MM diagnosis was 6.0 y (range: 0.3–22.8). Patients had received a median of 4.0 (range: 2–13) prior lines of therapy; all patients were triple-class exposed, 166 (73.8%) were triple-class refractory, and 208 (92.4%) were refractory to last line of therapy. The ORR with real-life SOC salvage therapy was 20.1% (95% CI: 15.0–26.0) in the response-evaluable population (n = 219). Treatment-emergent adverse events (TEAEs) were reported in 148 (65.8%) patients, 95 (42.2%) were grade ≥3. The most common grade ≥3 TEAEs were anemia, thrombocytopenia, and neutropenia. Fifteen deaths (6.7%) occurred due to TEAEs during the study. Treatment is ongoing in 121 (53.8%) patients. Conclusions: The interim results of this first, prospective study of real-life SOC treatment in heavily pretreated, triple-class exposed patients with RRMM demonstrate that patients continue to progress after multiple lines of therapy and have poor outcomes. Therefore, there is a need for new treatments with novel mechanisms of action for this patient population. Clinical trial information: NCT04035226.

Daratumumab is a human CD38-targeted monoclonal antibody approved as monotherapy for heavily pretreated relapsed and refractory multiple myeloma. We report findings for the Spanish cohort of an open-label treatment protocol that provided early access to daratumumab monotherapy and collected safety and patient-reported outcomes data for patients with relapsed or refractory multiple myeloma. At 15 centers across Spain, intravenous daratumumab (16 mg/kg) was administered to 73 patients who had >= 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, or who were double refractory to both. The median duration of daratumumab treatment was 3.3 (range: 0.03-13.17) months, with a median number of 12 (range: 1-25) infusions. Grade 3/4 treatment-emergent adverse events were reported in 74% of patients and included lymphopenia (28.8%), thrombocytopenia (27.4%), neutropenia (21.9%), leukopenia (19.2%), and anemia (15.1%). Common (>5%) serious treatmentemergent adverse events included respiratory tract infection (9.6%), general physical health deterioration (6.8%), and back pain (5.5%). Infusion-related reactions occurred in 45% of patients. The median change from baseline in all domains of the EQ-5D-5L and EORTC QLQ-C30 was mostly 0. A total of 18 (24.7%) patients achieved a partial response or better, with 10 (13.7%) patients achieving a very good partial response or better. Median progression-free survival was 3.98 months. The results of this early access treatment protocol are consistent with previously reported trials of daratumumab monotherapy and confirm its safety and antitumoral efficacy in Spanish patients with heavily treated relapsed or refractory multiple myeloma., This study was funded by Janssen Research & Development, LLC. Editorial and medical writing support were provided by J. Matthew Kuczmarski, PhD, of MedErgy, and were funded by Janssen Global Services, LLC. The data sharing policy of Janssen Pharmaceutical Companies of Johnson& Johnson is available at https://www.janssen.com/clinical-trials/transparency.As noted on this site, requests for access to the study data can be submitted through the Yale Open Data Access (YODA) Project site at http://yoda.yale.edu.

© 2018 The Authors., [Background]: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. [Patients and Methods]: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months., [Results]: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide., [Conclusion]: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits., Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc.

Summary This phase II study explored the effects of bortezomib consolidation versus observation on myeloma-related bone disease in patients who had a partial response or better after frontline high-dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35-day cycles of bortezomib 1·6 mg/m2 intravenously on days 1, 8, 15 and 22, or an equivalent observation period, and followed up for disease status/survival. The modified intent-to-treat population included 104 patients (51 bortezomib, 53 observation). There were no meaningful differences in the primary endpoint of change from baseline to end of treatment in bone mineral density (BMD). End-of-treatment rates (bortezomib versus observation) of complete response/stringent complete response were 22% vs. 11% (P = 0·19), very good partial response or better of 80% vs. 68% (P = 0·17), and progressive disease of 8% vs. 23% (P = 0·06); median progression-free survival was 44·9 months vs. 21·8 months (P = 0·22). Adverse events observed ≥15% more frequently with bortezomib versus observation were diarrhoea (37% vs. 0), peripheral sensory neuropathy (20% vs. 4%), nausea (18% vs. 0) and vomiting (16% vs. 0). Compared with observation, bortezomib appeared to have little impact on bone metabolism/health, but was associated with trends for improved myeloma response and survival.

Background: Substantial improvements in both progression free survival (PFS) and overall survival (OS) have been observed in patients with multiple myeloma over recent years. Despite these therapeutic advances, multiple myeloma remains incurable, and most patients eventually progress through standard drug classes of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), anti-CD38 monoclonal antibodies (mAbs) and others. Understanding the effectiveness of current standards of care in heavily pretreated patients with relapsed and / or refractory multiple myeloma (RRMM) remains an area of unmet need, and there are currently no prospective data reflecting real-world practice in this patient population progressing after PIs, IMiDs and anti-CD38 mAbs. Study design: This prospective multinational efficacy and safety study of real-life current standards of care (real-life SOC) will be conducted in the USA and Europe in approximately 230 adult patients with RRMM who received at least 3 prior lines of therapy or are double refractory to PI & IMiD and have received at least a PI, an IMiD, and CD38 mAbs and with documented progressive disease (PD) since their last line of therapy and have an ECOG score of 0-1. Also, subjects with documented evidence of PD (as above) within the previous 6 months and who are refractory or non-responsive to their most recent line of treatment are eligible. There are no exclusion criteria due to the observational nature of the study. The treatments that these patients receive in real life will be assessed for safety and efficacy over a two-year period. Real-life SOC treatments are defined as the treatment used in local clinical practice by the investigator for adult subjects with RRMM, who meet the eligibility criteria. Subject participation will include a Screening Phase, a Treatment Phase, and a Follow-up Phase up to 24 months from day 1, cycle 1 of the treatment. The Follow-up Phase will continue until study completion, which is defined as 24 months after the last subject receives the first dose of real life SOC treatment. Subjects will be treated until disease progression, unacceptable toxicity, or other reasons. The primary objective of the study is to evaluate the overall response rate (ORR) of real-life SOC treatments in participants with RRMM patients. The secondary and exploratory objectives of the study are the further evaluation of the clinical benefit, patient-reported outcomes (PROs), safety and the potential correlation of rate of minimal residual disease (MRD) negativity with duration of response (DOR), PFS and OS. Methods: Demographic and patient characteristics, clinical response parameters, PRO measures, health care resource utilization, and safety data will be descriptively summarized. Due to the observational nature of the study, there is no direct hypothesis being tested. Therefore, the sample size is based on the clinically acceptable precision of the 95% confidence interval for the primary objective of describing ORR under real-life current SOC treatment. For the primary endpoint exact 95% confidence intervals by the Clopper-Pearson method will be calculated. For therapies available to treat participants with RRMM the reported ORR is 30% or less. When the sample size is 230, using the large sample normal approximation, the width of a two-sided 95% confidence interval for the observed proportion will vary from 0.107 to 0.130 for an expected proportion varying from 0.20 to 0.40. Disclosures Moreau: AbbVie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Mateos:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmamar: Membership on an entity's Board of Directors or advisory committees; EDO: Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Weisel:Takeda: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; GSK: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Adaptive Biotech: Consultancy, Honoraria; Juno: Consultancy. San-Miguel:Amgen, Bristol-Myers Squibb, Celgene, Janssen, MSD, Novartis, Roche, Sanofi, and Takeda: Consultancy, Honoraria. Facon:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Boccadoro:Sanofi: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; AbbVie: Honoraria; Mundipharma: Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Goldschmidt:ArtTempi: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; Mundipharma: Research Funding; MSD: Research Funding; Novartis: Honoraria, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; Chugai: Honoraria, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; Molecular Partners: Research Funding; John Hopkins University: Other: Grants and/or provision of Investigational Medicinal Product; Dietmar-Hopp-Foundation: Other: Grants and/or provision of Investigational Medicinal Product; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding. Cavo:Janssen, Celgene: Other: Travel Accommodations; Janssen, Celgene, Amgen, Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen, Celgene: Speakers Bureau; Celgene, Janssen, Amgen, BMS, Abbvie, Takeda: Honoraria. Kaiser:Abbvie, Celgene, Takeda, Janssen, Amgen, Abbvie, Karyopharm: Consultancy; Celgene, Janssen: Research Funding; Takeda, Janssen, Celgene, Amgen: Honoraria, Other: Travel Expenses. Gay:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees. Scheid:Janssen: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Amgen: Consultancy, Honoraria; Celgene: Honoraria; Takeda: Honoraria, Research Funding. Broyl:Celgene, amgen, Janssen,Takeda: Honoraria. Van De Donk:AMGEN: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. Potamianou:Janssen-Cilag: Employment. Sakabedoyan:Janssen-Cilag: Employment. Strulev:Jansen Pharmaceutica NV: Employment. Nesheiwat:Legend Biotech: Employment, Equity Ownership. Bergmans:Janssen-Cilag: Employment. Rizvi:Legend Biotech: Employment, Equity Ownership. Pilatowicz:Janssen-Cilag: Employment. Sonneveld:Amgen: Honoraria, Research Funding; BMS: Honoraria; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Karyopharm: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; SkylineDx: Research Funding.

AIMS: Studies have shown that bortezomib retreatment is effective in relapsed/refractory multiple myeloma (MM). The observational, prospective electronic VELCADE® OBservational Study (eVOBS) study assessed bortezomib-based therapies for patients with MM in everyday practice. Here, we report on those patients receiving retreatment with bortezomib. METHODS: Consenting adults scheduled to receive bortezomib for MM were enrolled at 162 sites across Europe, Canada, Brazil, Russia, and Turkey between 2006 and 2010. Retrospective data on prior therapies and prospective observational data after bortezomib initiation were captured electronically at baseline, after every bortezomib cycle, and every 12 weeks after discontinuation or progression. Investigator-assessed responses and adverse events (AEs) were evaluated. RESULTS: Ninety-six of 873 patients enrolled to eVOBS received bortezomib as first retreatment for progressive disease during the prospective observation period. Median age was 62 years, 53% were male, and median number of prior therapies at retreatment was 4. Overall, 41% of patients initiated bortezomib retreatment in combination with dexamethasone, 16% in combination with lenalidomide, and 21% received monotherapy. Rate of partial response or better (≥PR) was 75% at initial bortezomib therapy, including 44% complete response (CR)/near CR (nCR); at retreatment, ≥PR rate was 46%, including 15% CR/nCR. Median progression-free survival was 11.4 months (95% confidence interval [CI]: 9.1-12.7) from start of initial bortezomib treatment and 6.4 months (95% CI: 4.4-7.2) from start of retreatment. Median overall survival from start of retreatment was 17.6 months (95% CI: 14.4-23.5). Of the 96 patients retreated with bortezomib, 77% reported an AE. Peripheral neuropathy during bortezomib retreatment occurred in 49% of patients, including 10% grade 3/4. CONCLUSION: These data suggest that retreatment with bortezomib is a feasible option for patients with relapsed/refractory MM. ispartof: HEALTH SCIENCE REPORTS vol:2 issue:1 ispartof: location:United States status: published

To review evidence on the use of erythropoietic stimulating agents (erythropoietin or darbepoetin) in children with cancer.A systematic review of the published literature was performed using MEDLINE (1966-July 2007) and references from a Cochrane systematic review (focusing mainly on adults) published in 2006.The review identified 12 studies, comprising five randomized trials, six case control studies and one open-label, dose-escalation study. All the studies that used adequate doses of recombinant human erythropoietin (rhEPO) (usually 150 IU/kg three times per week) demonstrated benefits for rhEPO except for one study in which rhEPO was added to G-CSF in children with high-risk neuroblastoma. Despite the heterogeneity of the populations studied, in terms of age, tumour type and chemotherapy regimen, rhEPO use was associated with consistent benefits in terms of reduced transfusion requirements and improved haematological parameters. Only one case of darbepoietin use was reported.While more studies are required, it appears that rhEPO is safe in this vulnerable patient group and can benefit children with cancer by preventing or ameliorating anaemia.

Background: Subcutaneous administration of Eprex(®) (epoetin alfa) in patients with chronic kidney disease (CKD) was contraindicated in the European Union between 2002 and 2006 after increased reports of anti-erythropoietin antibody-mediated pure red cell aplasia (PRCA). The Prospective Immunogenicity Surveillance Registry (PRIMS) was conducted to estimate the incidence of antibody-mediated PRCA with subcutaneous administration of a new coated-stopper syringe presentation of Eprex(®) and to compare this with the PRCA incidence with subcutaneous NeoRecormon(®) (epoetin beta) and Aranesp(®) (darbepoetin alfa). Methods: PRIMS was a multicentre, multinational, non-interventional, parallel-group, immunogenicity surveillance registry. Adults with CKD receiving or about to initiate subcutaneous Eprex(®), NeoRecormon(®) or Aranesp(®) for anaemia were enrolled and followed for up to 3 years. Unexplained loss or lack of effect (LOE), including suspected PRCA, was reported, with antibody testing for confirmation of PRCA. Results: Of the 15 333 patients enrolled, 5948 received Eprex(®) (8377 patient-years) and 9356 received NeoRecormon(®)/Aranesp(®) (14 286 patient-years). No treatment data were available for 29 patients. Among 23 patients with LOE, five cases of PRCA were confirmed (Eprex(®), n = 3; NeoRecormon(®), n = 1; Aranesp(®), n = 1). Based on exposed time, PRCA incidence was 35.8/100 000 patient-years (95% CI 7.4-104.7) for Eprex(®) versus 14.0/100 000 patient-years (95% CI 1.7-50.6) for NeoRecormon(®)/Aranesp(®). The incidence of PRCA with Eprex(®) was not significantly different versus comparator ESAs (rate ratio: 2.56; 95% CI 0.43-15.31). An analysis based on observed time produced similar findings. Conclusion: This large, prospective registry demonstrates that PRCA is rare with subcutaneous administration of either the new coated-stopper syringe presentation of Eprex(®), or NeoRecormon(®) or Aranesp(®). This study was funded by Janssen, Pharmaceutical Companies of Johnson & Johnson.

Purpose: To evaluate the efficacy and tolerance of the docetaxel/gefitinib combination as second-line treatment in patients with advanced pancreatic cancer. Patients and Methods: Twenty-six patients pretreated with gemcitabine-based chemotherapy were enrolled in the study. Docetaxel (75 mg/m2, i.v.) was administered every 3 weeks for a maximum of 6 cycles and gefitinib (250 mg/day, p.o.) was given continuously. Results: Five (19.2%) patients achieved stable disease. The median duration of disease control was 4.8 months (range 1–13.2), the median time to disease progression 2.1 months (range 1–7.3) and the median survival time 2.9 months (range 1–13.9). Grade 3/4 neutropenia was recorded in 9 (34.6%) patients, although only 1 (3.8%) developed grade 2 febrile neutropenia. One (3.8%) patient experienced grade 3 fatigue and 2 (7.7%) grade 3 diarrhea. Grade 1/2 rash was observed in 13 (50%) patients. There were no treatment-related deaths. Conclusion: The docetaxel/gefitinib combination, although safe, has no activity as salvage treatment for advanced pancreatic cancer after failure of gemcitabine-based chemotherapy.

This study compared the costs of home palliative with conventional hospital care for cancer haematological patients in Greece. The study was a retrospective cost-minimisation analysis using data from the finance department and from patient notes for the period from January to June 2002. A non-parametric bootstrap method was used to estimate the incremental cost between home and conventional care. A sensitivity analysis was also used. The estimated incremental cost was euro 522 (95% confidence interval: euro 516-528). This was not substantially affected by varying the unit costs within reasonable limits and remained statistically significant under all scenarios tested in the sensitivity analysis. Our findings show that home palliative care is more expensive than conventional hospital care. Further studies should be carried out to examine the cost-effectiveness of the particular scheme as well as the preferences of patients and carers.

Cisplatin or carboplatin plus paclitaxel is considered the standard first-line treatment in ovarian cancer. Attempts to maximize tumor cytoreduction with first-line chemotherapy by incorporating new promising agents led to sequential drug administration with two or three doublets. In the present study, we aimed to evaluate the activity and the tolerance of two sequential doublets (paclitaxel/carboplatin and liposomal doxorubicin/carboplatin) administered as first-line treatment in patients with FIGO III/IV ovarian cancer. Treatment consisted of four cycles of carboplatin (6 AUC) plus paclitaxel (175 mg/m2; PC regimen) followed by four cycles with carboplatin (6 AUC) plus liposomal doxorubicin (40 mg/m2; LD/C regimen) every 3 weeks. Forty-one patients in FIGO III or IV were enrolled. In an intention-to-treat analysis, 20 (49%) complete (CR) and 12 (29%) partial (PR) responses were achieved (overall response rate, ORR: 78%; 95% confidence interval, CI: 64.1–91.9%); with the PC regimen (164 cycles); 7 (17%) patients have stable (SD) and 2 (5%) progressive (PD) disease. The LD/C regimen (124 cycles) was administered in 36 (88%) patients because of 2 early deaths and 3 patient withdrawals. Three additional patients, 2 with PR and 1 with SD after PC chemotherapy) achieved a CR. Upon completion of the LD/C chemotherapy there were 18 (44%) patients with CR and 9 (22%) with PR (ORR = 66%; 95% CI: 64–92%). The median duration of response was 27 months and the median time to progression 20 months. The probability of 2-year survival was 67%. Grade 3 and 4 neutropenia was observed in 34 and 14.6% of the patients, respectively, during the PC regimen, while during the treatment with LD/C the percentages for grade 3 and 4 neutropenia were 44.4 and 19.4%, respectively. Febrile neutropenia occurred only in patients treated with the PC regimen (4.9%). The incorporation of liposomal doxorubicin in this sequential doublet schedule of first-line treatment of ovarian carcinoma created a feasible and active regimen. Prospective randomized studies are required to assess its efficacy on patient survival.

Background Phase 2 data from the RETRIEVE study suggested that retreatment with bortezomib IV ± dexamethasone in relapsed/refractory MM is active, adequately tolerated and feasible. The combination of bortezomib IV with dexamethasone in RETRIEVE, although associated with increased toxicity, was more efficacious than single-agent bortezomib (Petrucci T, et al. Haematol. 2010;95:152). SC administration of bortezomib has also shown improved tolerability, in terms of decreased side effects and drop-out rates, compared with the IV route (Moreau P, et al. Lancet Oncol. 2011;12:431-440). Here we report results of a randomized, international, multicenter, open-label phase 3 study that investigated the effects of experimental retreatment with SC bortezomib + dexamethasone followed by prolonged bortezomib therapy vs standard bortezomib + dexamethasone retreatment (NCT01910987; MMY3033). This study was terminated prematurely with insufficient sample size to adequately compare the retreatment therapies; the results should therefore be considered descriptive. Methods Pts were randomized (1:2) to receive either standard or experimental retreatment, stratified by the number of prior therapy lines. In the standard group, pts received 8 x 21-day cycles of SC bortezomib 1.3 mg/m2 (days 1, 4, 8, 11) plus dexamethasone 20 mg (days 1, 2, 4, 5, 8, 9, 11, 12). In the experimental group, pts followed this schedule for the first 2 cycles, followed by 4 x 35-day cycles of SC bortezomib (days 1, 8, 15, 22) plus dexamethasone (days 1, 2, 8, 9, 15, 16, 22, 23); pts completing experimental therapy were re-randomized (1:1) to prolonged single-agent SC bortezomib 1.3 mg/m2 (either on days 1, 8, 15, 22 of 35-day cycles or every other week) until disease progression, unacceptable toxicity, start of alternative MM therapy, withdrawal, or death. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall response rate (ORR), duration of response (DOR), time to progression (TTP), overall survival (OS), time to next myeloma therapy (TTNT) and safety. Response and progression were assessed by investigators and the independent Data Monitoring Committee according to International Myeloma Working Group (IMWG) criteria. Descriptive analyses were performed in the intent-to-treat (ITT) population; time to event endpoints were analyzed using Kaplan-Meier methodology. Results In total, 80 pts were randomized (experimental n=53, standard n=27), of whom 31 in the experimental group went on to receive prolonged bortezomib. In the experimental and standard groups, 53% vs 67% were male, median age was 68 vs 65 yrs, and 45/42/13% vs 48/48/4% had an ECOG PS of 0/1/2. After a median follow-up of 21.2 and 20.0 mos in the experimental and standard arms, respectively, and with 45 (85%) and 20 (74%) progression/death events, the median PFS was 7.2 mos (95% CI: 5.7-9.0) vs 7.8 mos (4.9-11.7) (Figure). The ORR (complete + very good partial + partial responses) was 66% and 56% for experimental and standard retreatment, respectively. Median DOR was 6.5 vs 5.6 mos, median TTNT was 8.6 vs 9.0 mos, and median TTP was 7.4 vs 7.8 mos with experimental vs standard retreatment. Median OS at 18 months was 84% and 77%, following experimental and standard retreatment, respectively. All pts experienced at least one treatment-emergent adverse event (AE). The most common grade ≥3 AEs were (experimental vs standard; ≥5% in total population): thrombocytopenia (9% vs 22%), anemia (8% vs 7%), pneumonia (8% vs 4%) and atrial fibrillation (6% vs 7%); peripheral neuropathies (any grade; including peripheral neuropathy and peripheral sensory neuropathy) were reported in 23% vs 37% of pts. Serious AEs were reported in 34% vs 44% of pts in the experimental vs standard groups; the most common were atrial fibrillation (6% vs 4%), bronchitis (6% vs 0), pneumonia (8% vs 7%), and hypercalcemia (0 vs 7%). There were 6 on-study deaths due to treatment-emergent AEs (experimental: 5, standard: 1); all were considered unrelated to bortezomib or dexamethasone. Conclusions MMY3033 showed no significant efficacy benefit with experimental vs standard bortezomib retreatment therapy; however the study results were not sufficiently powered because of insufficient sample size. Efficacy and safety were consistent with previous reports of bortezomib/dexamethasone, with a slight reduction in thrombocytopenia events in the experimental retreatment group. Disclosures Cavo: Janssen-Cilag: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Millennium: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria. Gobbi:Janssen: Consultancy, Honoraria; Mundipharma: Consultancy, Research Funding; Takeda: Consultancy; Novartis: Consultancy, Research Funding; Gilead: Honoraria; Celgene: Consultancy; Roche: Honoraria. Potamianou:Janssen-Cilag Pharmaceuticals SACI: Employment. Lahaye:Janssen-Cilag: Employment. Couturier:Janssen-Cilag: Employment. Terpos:Celgene: Honoraria; Novartis: Honoraria; Genesis: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding.

and showed evidence of disease in 145 (93%). After a median follow-up of 3.5 years, the median OS for the entire group was 7 months. Untreated and treated patients had median OS of 2 and 8 months, respectively. At least one previous line of therapy for MM and > 1 cytogenetic abnormality were independently associated with worse OS. The median OS for patients with 0, 1 and 2 of these risk factors were 25 months, 5.5 months and 2 months, respectively. Conclusion: Neurological manifestations observed in patients with MM should raise a suspicion of CNS involvement. The diagnosis of CNS MM should be based on imaging studies and CSF cytology and flow cytometry. Although prognosis is generally poor, especially in patients with a long history of chemotherapy and unfavorable cytogenetic profile, survival of individuals free from these negative prognostic factors can be prolonged due to administration of systemic treatment and/or radiotherapy. Prospective multi-institutional studies are warranted to improve the outcome of patients with CNS MM. PO-089 Improved tumor response and survival outcomes with post-transplant bortezomib (Btz) consolidation versus observation (Obs) alone in patients with newly diagnosed multiple myeloma (MM): Results from a randomized, open-label, multicenter, parallel-group phase 2 study O. Sezer, E. Terpos, R. Hajek, G. Sucak, S. Cagirgan, W. Linkesch, O.M. Akay, G. Armbrecht, T. Plesner, J.A. Snowden, H. Nahi, Z. Gulbas, A. Potamianou, C. Couturier, R. Olie, C. Feys, N. Allietta, M. Beksac Department of Hematology and Stem Cell Transplantation, Memorial Hospital, Istanbul, Turkey; Department of Clinical Therapeutics, University of Athens School of Medicine, Alexandra General Hospital, Athens, Greece; Internal Medicine and Hematooncology, Masaryk University Hospital Brno and Faculty of Medicine University Hospital Ostrava, Czech Republic; Department of Hematology, Faculty of Medicine, Gazi University, Ankara, Turkey; Department of Hematology and BMT Center, Izmir Medicalpark Private Hospital, Izmir, Turkey; Department of Hematology, Medical University Clinic, Medical University of Graz, Graz, Austria; Hematology Department, Eskisehir Osmangazi University, Eskisehir, Turkey; Centre for Muscle and Bone Research, Charite e Campus Benjamin Franklin, Berlin, Germany; Department of Hematology, Vejle Hospital, Vejle and IRS/ SDU, Denmark; Department of Haematology, Royal Hallamshire Hospital, Sheffield, UK; Haematology Centre, Karolinska University Hospital, Stockholm, Sweden; Bone Marrow Transplantation Department, Anadolu Health Center, Kocaeli, Turkey; Janssen-Cilag Pharmaceutical SACI, Athens, Greece; Janssen-Cilag, Issy-lesMoulineaux, France; Janssen-Cilag AG, Zug, Switzerland; Janssen Research & Development, Division of Janssen Pharmaceutica NV, Beerse, Belgium; Covance for Janssen-Cilag, Issy-les-Moulineaux, France; Department of Hematology, Ankara University, Ankara, Turkey Background: Induction therapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a standard frontline treatment for eligible MM patients (pts). PostASCT consolidation can improve depth of response and long-term outcomes. This phase 2 study evaluated the effects of Btz consolidation vs Obs alone on MM-related bone disease; pre-specified secondary endpoints of disease status (myeloma response), PFS, and OS are reported here. Methods: Eligible pts were adults with newly diagnosed MM who had achieved PR after single/double ASCT. Pts were randomized 1:1 (stratified by baseline bisphosphonate use and age) to receive 4 x 35-d cycles of Btz 1.6 mg/m2 IV on d 1, 8, 15, and 22, or Obs alone, followed by 18-mos’ follow-up for disease status and survival monitoring. Response was investigator-assessed per IMWG 2009 criteria. A last observation carried forward approach was used for missing assessments. PFS and OS were estimated using Kaplan-Meier analysis; exploratory p-values were determined using the log-rank test. Results: Between July 2009 and May 2012, 106 pts were randomized (52 Btz, 54 Obs). 2 pts were withdrawn prior to d 1, thus the modified intent-to-treat (mITT) population included 104 pts (51 Btz, 53 Obs): median age 58 vs 57 yrs; 71% vs 66% prior Btz-based induction. 41 (79%) and 46 (85%) pts completed the respective Btz consolidation and Obs phases as planned. CR+sCR rates at screening were 16% (Btz) and 15% (Obs). After the treatment/Obs phase, response rates were (Btz vs Obs): CR+sCR 22% vs 11%; VGPR 80% vs 68%; PD 8% vs 23%. PFS appeared longer with Btz consolidation vs Obs, both from randomization (median 44.9 vs 21.8 mos) and from first antiMM treatment (median 50.7 vs 35.0 mos) (Figure). After 21 (20%) deaths (11 Btz; 10 Obs), mean OS from randomization was 40.1 vs 36.6 mos and from first anti-MM treatment was 51.7 vs 47.1 mos; median OS was not reached in either arm at both time points. Pvalues for between-arm differences in response rates, PFS, and OS were all >0.05, likely due to small sample size. Conclusion: Compared with Obs alone, Btz consolidation was associated with trends for improved response depth and longer PFS and OS in newly diagnosed MM pts. Our response and PFS findings compare favorably with recent phase 3 data of Btz consolidation vs Obs in 15th International Myeloma Workshop, September 23-26, 2015 e129

patients, serum lactic dehydrogenase was elevated (>300 U/L) in eight patients and found to correlate with the serum concentrations of 2-microglobuline, hemoglobin and creatinine. Patients with values below 300 U/L had a median survival time of 88 months (Mean: 87.8, SD: 43.8, CV: 0.5) compared to 90 months (Mean: 87 months, SD: 42.3, CV: 0.5) for those with levels above 300 U/L. Conclusion: Serum lactic dehydrogenase at diagnosis, thus, had no prognostic information in multiple myeloma when related to overall survival. 2. Multiple Myeloma Therapy in Newly Diagnosed Patients including Transplantation

Background: We reported better PFS and OS in transplant eligible patients with newly diagnosed Multiple Myeloma (MM) who were treated with bortezomib during induction and maintenance, when compared with standard treatment in the HOVON-65/GMMG-HD4 trial. (P. Sonneveld et al., J Clin Oncol 30:2946-2955, 2012). Here the long-term follow up data are presented. Methods: 827 eligible patients were randomized to induction therapy with VAD (vincristine, doxorubicin, dexamethasone) or PAD (bortezomib, doxorubicin, dexamethasone) followed by high-dose melphalan (once or twice) and autologous stem cell transplant. Maintenance consisted of daily thalidomide (T) 50 mg (VAD arm) or 2-weekly bortezomib (B) 1.3 mg/m2 (PAD arm) for 2 years. The primary endpoint was progression-free survival (PFS) adjusted for ISS stage. Results: After a median follow up of 91.4 months (maximum 119) 410 patients are alive. Response rates were VAD/HDM/T: CR 25%, ≥VGPR 56%, ≥PR 83%; PAD/HDM/B: CR 37%, ≥VGPR 76%%, ≥PR 91%, The median duration of maintenance therapy was 14 months (thalidomide) and 23 months (bortezomib), respectively. Main reasons for discontinuation were toxicity (T: 31%; B: 11%), disease progression (T: 33%; B: 36%) or normal completion (T: 28%; B: 48%). Of 827 patients in the analysis, 206 are alive without progression/relapse. PFS was significantly better in the bortezomib arm, i.e. median 34 versus 28 months (HR=0.77, 95% CI=0.65-0.90, p=0.001). Median overall survival (OS) was 90 months in the bortezomib arm vs 83 months in the control arm, but 42% at 9 years in both arms. We used the restricted mean survival time (RMST) method to compare OS between the two treatment arms In univariate analysis. The difference in RMST8y was 4.8 months (95% CI 0.2-9.5, p=0.04) in favor of the bortezomib arm. A landmark analysis in patients who had received HDM starting at 12 months showed a significant PFS advantage of bortezomib in all patients (p=0.02), in patients in VGPR/PR (p=0.02) but not in CR (p=0.19). For OS there was no advantage for bortezomib in either group. PFS at 60 months in bortezomib treated patients was not different when single vs double HDM/ASCT was administered, i.e. 28% vs 27%. However, OS at 60 months was 71% vs 60% in favor of double HDM/ASCT (p=0.04). Subgroup analysis was performed based on presence/absence of adverse FISH (CA) in 395 patients treated with double HDM/ASCT. PFS at 60 months for each abnormality (CA or no CA) in bortezomib vs standard arm is given in Table 1 Table 1.PFS at 60 months, %OS at 60 months, %FISHnBortezomib armpStandard armBortezomib armpStandard Armt(4;14) yes/no50/29516% vs 27%0.048% vs 24%52% vs 75%0.0133% vs 64%add(1q) yes/no113/23116% vs 32%0.00510% vs 28%57% vs 79%0.00143% vs 70%del(17p) yes/no39/31222% vs 27%0.475% vs 24%65% vs 72%0.4818% vs 66% These data show that bortezomib treatment combined with double HDM/ASCT significantly improves PFS and OS in patients with del(17p) and almost abrogates the negative impact of this CA. In t(4;14) and add(1q) some improvement is observed, however the negative impact remains significant. In high-risk patients presenting with elevated creatinine >2 mg/dL bortezomib significantly improved PFS at 60 months (32% vs 5%) (p=0.001) and OS at 60 months (66% vs 21% months (p Conclusions: We conclude that bortezomib leads to a significant and lasting improvement of PFS and OS. Bortezomib significantly reduces the high-risk impact of del(17p) and renal impairment on survival. This trial was registered as NTR213; EudraCT no. 2004-000944-26.and supported by the Dutch Cancer Foundation, the German Federal Ministry of Education and Research and an unrestricted grant from Janssen. The GMMG group received grants for this trial by Novartis, AMGEN, Chugai and Roche. Disclosures Sonneveld: SkylineDx: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Research Funding; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Salwender:Celgene: Honoraria; Janssen Cilag: Honoraria; Bristol Meyer Sqibb: Honoraria; Amgen: Honoraria; Novartis: Honoraria. Blau:MSD: Honoraria; Celgene: Honoraria, Research Funding; AMGEN: Honoraria; JAZZ pharm: Honoraria; BMS: Honoraria; Shire: Honoraria; Baxalta: Honoraria; Janssen: Honoraria, Research Funding. Zweegman:celgene: Honoraria, Research Funding; takeda millennium: Honoraria, Research Funding; onyx: Honoraria. Weisel:Noxxon: Consultancy; Janssen Pharmaceuticals: Consultancy, Honoraria, Other: Travel Support, Research Funding; Novartis: Other: Travel Support; Onyx: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel Support; BMS: Consultancy, Honoraria, Other: Travel Support; Celgene: Consultancy, Honoraria, Other: Travel Support, Research Funding. Broijl:Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Scheid:Janssen: Honoraria; Celgene: Honoraria. Potamianou:Janssen: Employment. Hose:Takeda: Other: Travel grant; EngMab AG: Research Funding. Kersten:takeda millennium: Research Funding; janssen: Honoraria, Research Funding; roche: Honoraria, Research Funding. Duehrsen:Alexion: Honoraria; janssen: Honoraria. Lokhorst:Janssen: Honoraria, Research Funding; Genmab: Honoraria, Research Funding; Amgen: Honoraria. Goldschmidt:celgene: Honoraria, Research Funding; janssen: Honoraria, Research Funding; novartis: Honoraria, Research Funding; chugai: Honoraria, Research Funding; onyx: Honoraria, Research Funding; millennium: Honoraria, Research Funding; BMS: Honoraria, Research Funding.

Background A lack of objective data exists on differences in treatment practices and outcomes for MM between countries. The EMMOS study aimed to document and describe current treatment regimens and disease progression patterns of MM pts at different stages of the disease in real-world medical practice. Methods Adult pts initiating any new MM therapy, irrespective of treatment line at study entry or therapy type received, were eligible for inclusion in the EMMOS registry. A multi-staged pt/site recruitment model was applied to minimize selection bias; enrollment was stratified by country, region, and practice type. Pts' medical/disease features, treatment history, and remission status were recorded at baseline. Prospective data on treatment, efficacy, and safety were collected electronically every 3 mos until 2 yrs after the last pt enrolled. Responses were investigator-assessed (no predefined criteria). Here we report data from the final analysis of EMMOS. Pts were grouped according to receipt of high-dose chemotherapy/stem cell transplantation in any treatment line (SCT pts, non-SCT pts). Within a given line, pts may have received induction, SCT, consolidation, and/or maintenance therapy; if multiple drug combinations were used within a line, the line grouping was based on the combination received in cycle 1. Results 2358 pts were enrolled between Oct 2010-Oct 2012 in 22 countries in Europe and Africa; the last pt completed follow-up in Oct 2014. Of these, 775 pts had undergone SCT in any treatment line. Baseline characteristics in the prospective phase by starting line are shown in the Table. As expected, there was a higher proportion of younger pts (≤65 yrs) in the SCT vs non-SCT group across all treatment lines, and in both groups a higher proportion of pts in 4th + vs earlier lines with ISS stage III disease. While cytogenetics were evaluated in a small number of pts overall (670/2358 [28%]), these assessments were performed significantly more frequently in SCT vs non-SCT pts (p Conclusion This large, real-world, observational study provides for the first time a comprehensive picture of the baseline characteristics and therapy of MM pts treated in Europe, the Middle-East, and Africa. These data provide a framework towards the design of future protocols aiming to improve outcomes in MM. Table. Baseline characteristics by starting line Non-SCT pts SCT pts L1 (n=897) L2 (n=319) L3 (n=184) L4+ (n=166) Total* (N=1566) L1 (n=378) L2 (n=161) L3 (n=107) L4+ (n=120) Total* (N=775) Age ≤65 yrs, % 36 34 35 39 36 87 76 72 71 80 ISS Stage II/III, % 36/44 34/47 43/38 22/52 35/44 33/35 44/27 34/26 23/48 34/34 Salmon-Durie Stage 2/3, % 28/64 25/66 24/71 29/62 27/65 22/68 25/67 20/65 11/81 20/69 Bone lesion history, % 64 72 75 70 68 66 74 77 80 71 Cytogenetics assessed, % 24 19 19 14 21 51 35 43 33 44 Del 17p 8 8 9 13 8 10 7 4 13 9 t(4,14) 6 7 9 4 6 7 14 13 8 9 ISS, International staging system; L, line *17 non-SCT and 9 SCT pts were enrolled but did not receive a line of therapy within 75 days of baseline Disclosures Mohty: Celgene: Honoraria; Janssen: Honoraria. Terpos:Amgen: Honoraria, Research Funding; Janssen: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Mateos:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Palumbo:Array BioPharma: Consultancy; Onyx Pharmaceuticals: Consultancy; Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Genmab A/S: Consultancy; Bristol-Myers Squibb: Consultancy; Amgen: Consultancy; Sanofi Aventis: Consultancy. Lejniece:Amgen: Honoraria; Sandoz: Honoraria. Beksac:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Dimopoulos:Novartis: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Onyx: Honoraria; Celgene: Honoraria; Genesis Pharma: Research Funding. De Stefano:Shire: Speakers Bureau; Roche: Research Funding; Bruno Farmaceutici: Research Funding; Janssen Cilag: Research Funding; Amgen: Speakers Bureau; GlaxoSmithKline: Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Celgene: Speakers Bureau. Salwender:Celgene: Honoraria; Janssen Cilag: Honoraria; Bristol Meyer Sqibb: Honoraria; Amgen: Honoraria; Novartis: Honoraria. Pečeliūnas:Johnson & Johnson: Honoraria, Research Funding. Willenbacher:CTI: Consultancy, Other: Travel, Accommodations, Expenses; Gilead: Consultancy, Other: Travel, Accommodations, Expenses, Speakers Bureau; Amgen: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Janssen: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Roche: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Celgene: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Novartis: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding. Da Silva:Janssen Pharmaceuticals: Research Funding. Louw:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Nemet:Sanofi: Honoraria; Pliva: Honoraria; Pfizer: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Potamianou:Janssen: Employment. Couturier:Janssen-Cilag: Employment. Olie:Johnson & Johnson: Equity Ownership; Janssen-Cilag: Employment. Feys:Janssen Pharmaceutica N.V.: Employment, Equity Ownership. Thoret-Bauchet:Janssen-Cilag: Employment.

Purpose: To evaluate the efficacy and tolerance of the gemcitabine/oxaliplatin (GEMOX) combination as second-line chemotherapy for patients with advanced colorectal cancer (CRC) pretreated with an irinotecan (CPT-11)/5-fluorouracil (5-FU)/leucovorin (LV) regimen. Patients and Methods: Patients with documented disease progression during or after first-line treatment with CPT-11 and 5-FU/LV were enrolled. Gemcitabine (1,000 mg/m2 days 1 and 8) and oxaliplatin (100 mg/m2 day 1) were administered every 3 weeks. Results: Partialresponses were observed in 6 of the 34 (17.7%) patients enrolled (intention-to-treat analysis; overall response rate: 17.7%; 95% confidence interval 4.8–30.5%). Eight (23.5%) patients experienced disease stabilization and 20 (59%) disease progression (tumor growth control rate = 41.2%). The median duration of response was 5.5 months, and the median time to tumor progression 2.7 months. The median overall survival was 9.1 months (1-year survival rate: 44.0%). Grade 3 neutropenia and thrombocytopenia occurred in 18 and 15% of the patients, respectively. Other severe non-hematologic toxicities were rare. Conclusion: The interesting tumor growth control rate and the favorable toxicity profile of the GEMOX regimen in pretreated patients with advanced CRC strongly suggest that this regimen may provide an alternative therapeutic option for this group of patients.

The docetaxel-cisplatin combination is active against several tumors including gastric cancer but it is followed by severe myelosuppression. Recent experience with weekly taxanes has demonstrated a mild myelotoxicity with high dose intensity. We investigated in a phase I study a weekly schedule of docetaxel on days 1, 8 and 15 and cisplatin on day 1 every 4 weeks in 19 patients with advanced gastric cancer with no prior chemotherapy. Cohorts of patients were treated with escalating doses of docetaxel (starting dose 30 mg/m(2) per week and increments of 10 mg/m(2) per week) and cisplatin (starting dose 70 mg/m(2) and increments of 5 mg/m(2)). Febrile neutropenia was the only dose-limiting event occurring in four (20%) patients; the dose-limiting toxicity was reached at dose level three (docetaxel 40 mg/m(2) per week and cisplatin 75 mg/m(2)). The maximum-tolerated dose was 40 mg/m(2) per week for docetaxel and 70 mg/m(2) every 4 weeks for cisplatin. Grade 3/4 neutropenia occurred in six patients (30%); early death occurred in one patient with septic shock because of neutropenia and another with acute coronary ischemia. Two (11%) complete and two (11%) partial responses were documented (ORR 22%; 95% CI 3-39%), with a median response duration of 5 months and median time to progression of 7 months. In conclusion, the combination of weekly docetaxel plus cisplatin is feasible with moderate toxicity and merits further investigation in phase II studies in advanced gastric cancer.

Introduction The activity of bortezomib (VELCADE®, Vc) ± dexamethasone (Dex) in relapsed MM is well established. Results from several studies suggest that adding Dex to Vc (Vc-Dex) can improve response rates in pts with suboptimal response to Vc alone; however, randomized comparative data in relapsed MM are lacking, and, although Vc-Dex is widely used in routine clinical practice, the benefit of adding Dex from first relapse remains unclear. We conducted a retrospective analysis of the efficacy and safety of second-line treatment with Vc-Dex vs Vc among propensity score-matched pairs to control for differences in baseline characteristics and allow meaningful cross-study comparisons. Methods Pt-level data from 3 clinical trials of single-agent Vc (APEX, Richardson et al. NEJM 2005; DOXIL–MMY3001, Orlowski et al. JCO 2007) and Vc-Dex (MMY2045, Dimopoulos et al. Haematologica 2013) were used in this analysis; follow-up for each study was complete. Only pts with 1 prior therapy were included. In all studies, pts received Vc 1.3 mg/m2 IV on days 1, 4, 8, 11 in 21-day cycles. In MMY2045, pts additionally received Dex 20 mg PO on days 1, 2, 4, 5, 8, 9, 11, 12 in 21-day cycles. Responses were per EBMT/IMWG criteria. Adverse events (AEs) were graded by NCI-CTCAE v2.0/3.0. Clinical variables associated with study drug tolerability or outcomes, which were collected consistently across all studies, were used in logistic regression analysis to calculate a propensity score against which pts’ data were matched; these 13 variables were age, body surface area (BSA), ECOG PS, myeloma type, presence of extramedullary plasmacytomas, % plasma cells in bone marrow biopsy, prior transplant, prior immunomodulatory drugs (IMiDs), prior Dex, and baseline hemoglobin levels, platelet count, creatinine clearance, and albumin levels. Efficacy and safety were then compared between the matched groups. Kaplan-Meier methodology was used for time-to-event analyses. Results Across the 3 studies, 384 pts received 1 prior therapy and were eligible for inclusion. Propensity score matching identified 109 pt pairs; baseline characteristics are shown in the table. For Vc-Dex vs Vc, respectively, median time since diagnosis was 2.7 vs 2.0 years, median treatment duration was 19.6 vs 17.6 weeks, and median cumulative Vc dose was 27.02 vs 28.60 mg/m2. Overall response rate (ORR) was significantly higher for Vc-Dex vs Vc (75% vs 41%, p Conclusion In this analysis of MM pts at first relapse, Vc-Dex was associated with significantly higher ORR and longer median TTP and PFS compared with Vc alone. The lack of difference in OS may be due to subsequent salvage therapies received. Addition of Dex to Vc was not associated with increased toxicity. These data indicate the potential benefit of using Vc-Dex from first relapse in MM. Disclosures: Dimopoulos: ORTHO-BIOTECH: Consultancy, Honoraria. Orlowski:Array Biopharma: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Resverlogix: Research Funding; Onyx Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Millennium: The Takeda Oncology Company: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Celgene Corporation: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Genentech: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Merck: Membership on an entity’s Board of Directors or advisory committees. Facon:Amgen: 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; Onyx: Membership on an entity’s Board of Directors or advisory committees; Millennium: The Takeda Oncology Company: Membership on an entity’s Board of Directors or advisory committees; Celgene: Membership on an entity’s Board of Directors or advisory committees; Janssen: Membership on an entity’s Board of Directors or advisory committees; Novartis: Membership on an entity’s Board of Directors or advisory committees. Sonneveld:Janssen: Consultancy, Research Funding; Millennium: The Takeda Oncology Company: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Onyx: Consultancy, Research Funding. Anderson:Celgene: Consultancy; Onyx: Consultancy; Sanofi Aventis: Consultancy; Gilead: Consultancy; Acetylon: Equity Ownership; Oncopep: Equity Ownership. Beksac:Janssen: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Benboubker:Celgene: Consultancy. Potamianou:Janssen Pharmaceuticals: Employment. Couturier:Janssen EMEA: Employment. Feng:Janssen R & D, LLC: Employment. Ataman:Janssen-Cilag: Employment. van de Velde:Johnson & Johnson: Equity Ownership; Janssen Research & Development: Employment. Richardson:Johnson & Johnson: Membership on an entity’s Board of Directors or advisory committees; Millennium: The Takeda Oncology Company: Membership on an entity’s Board of Directors or advisory committees; Celgene: Membership on an entity’s Board of Directors or advisory committees.

La trajectoire d’un cas d’homosexualite feminine est presentee, indiquant le cheminement parallele et l’eventuelle rencontre entre, d’une part, l’imaginaire suscite par l’evocation d’un mythe et, d’autre part, le reel d’un corps malade.