Abstract: Left ventricular (LV) mass is a prognostic biomarker for incident heart disease and all-cause mortality. Large-scale genome-wide association studies have identified few SNPs associated with LV mass. We hypothesized that a polygenic discovery approach using LV mass measurements made in a clinical population would identify risk factors and diseases associated with adverse LV remodeling. We developed a polygenic single nucleotide polymorphism-based predictor of LV mass in 7,601 individuals with LV mass measurements made during routine clinical care. We tested for associations between this predictor and 894 clinical diagnoses measured in 58,838 unrelated genotyped individuals. There were 29 clinical phenotypes associated with the LV mass genetic predictor at FDR q  〈  0.05. Genetically predicted higher LV mass was associated with modifiable cardiac risk factors, diagnoses related to organ dysfunction and conditions associated with abnormal cardiac structure including heart failure and atrial fibrillation. Secondary analyses using polygenic predictors confirmed a significant association between higher LV mass and body mass index and, in men, associations with coronary atherosclerosis and systolic blood pressure. In summary, these analyses show that LV mass-associated genetic variability associates with diagnoses of cardiac diseases and with modifiable risk factors which contribute to these diseases.

Abstract: Purpose: This study aimed to determine the benefit of early therapeutic intervention with the combination of elotuzumab, lenalidomide, and dexamethasone in patients with high-risk smoldering multiple myeloma (SMM). The overarching objective of this trial is to determine progression free survival to symptomatic myeloma (MM). Furthermore, the study examined the activity and safety of the combination therapy in patients with high-risk SMM. Patients & Methods: Patients enrolled on study met eligibility for high-risk SMM based on the newly defined criteria proposed by Rajkumar et al, Blood 2014. Patients were administered weekly elotuzumab (10 mg/kg) on days 1, 8, 15, and 22 for the first two 28-day cycles while receiving lenalidomide on days 1-21. An initial cohort of patients were randomized to a low dose dexamethasone treatment arm (Arm B) based on the following stratification factors: age 〉 65 years and high-risk cytogenetics based on t(4:14), t(14:16), 17p deletion or p53 mutation, and +1q amplification. For cycles 3-8, patients on both treatment arms were administered elotuzumab infusions on days 1, 8, and 15. Patients on treatment Arm A received dexamethasone (40mg) on days 1, 8 and 15. After 8 cycles or best response, patients were given the option to mobilize with either cyclophosphamide or plerixafor and collect stem cells for future transplant. Patients on both treatment arms were then allowed to continue on maintenance therapy where they were administered elotuzumab (20 mg/kg) on day 1, in combination with lenalidomide days 1-21 of a 28 day cycle. After 11 patients were enrolled on each arm, arm B closed due to similar activity and toxicity to the high-dose dexamethasone arm based on published data demonstrating that high-dose dexamethasone, given once a week, does not have a detrimental effect on the immune system in patients with smoldering myeloma. Results: In total, 39 patients were enrolled on this study from January 2015 to date, with the participation of eight sites. The median age of patients enrolled was 62 years (range 26 to 75) with 15 males (38%) and 24 females (62%). The median number of cycles completed is 6 (range 1 to 19). Therapy related grade 3 toxicities included hypophosphatemia (23%), neutropenia (8%), infection (8%), anemia (3%), pulmonary embolism (3%), rash (3%), and diarrhea (3%). No related grade 4 or 5 toxicities have occurred thus far. Stem cell collection was successful in all patients collected to date. Unrelated toxicities include one instance of grade 4 prolonged QTc Interval. Of the 34 evaluable patients enrolled to both arms of the study, the clinical benefit rate is 97%. The overall response rate is 71%, including 9 very good partial responses (26%) and 15 partial responses (44%). The VGPR cases are currently under evaluation of possible complete responses due to the potential interference of elotuzumab with immunoelectrophoresis. Thus far, no patients have progressed to active multiple myeloma during, or after, protocol therapy. Conclusion:The combination of elotuzumab, lenalidomide, and dexamethasone is very well tolerated among patients with high-risk SMM. The high response rates among this patient population, who would otherwise remain untreated, is a promising starting point for the paradigm shift towards early therapeutic intervention in patients with high-risk SMM. Disclosures Ghobrial: Amgen: Honoraria; Celgene: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Novartis: Honoraria; Takeda: Honoraria; Noxxon: Honoraria. Matous:Seattle Genetics: Research Funding, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Takeda Pharmaceuticals International Co.: Speakers Bureau. Rosenblatt:Astex: Research Funding; BMS: Research Funding; DCPrime: Research Funding. Usmani:Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Britsol-Myers Squibb: Consultancy, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Skyline: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Research Funding, Speakers Bureau; Array: Research Funding; Novartis: Speakers Bureau; Pharmacyclics: Research Funding; BioPharma: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Munshi:OncoPep Inc.: Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

Abstract: Abstract 1322 Poster Board I-344 Background Veltuzumab, a 2nd-generation humanized anti-CD20 monoclonal antibody with structure-function differences from rituximab, has demonstrated clinical activity at low doses in non-Hodgkin's lymphoma (Morschhauser et al., J Clin Oncol, 2009; 27:3346-53). Since chimeric anti-CD20 rituximab is therapeutically active in ITP, we conducted a clinical trial of low-dose veltuzumab in ITP, initially administered by intravenous (IV) infusion, but following development of a high-concentration formulation, now administered by subcutaneous (SC) injection. Methods A multicenter, phase I/II study was undertaken to evaluate the safety and tolerability of low-dose veltuzumab in adults who had ITP for at least 6 months, had failed ≥1 standard therapy, and presented with platelets ≤30K/≤L, but without major bleeding. All patients received 2 doses of veltuzumab 2 weeks apart (without steroids) and were followed for up to 12 weeks, with responding patients continuing in long-term follow-up. Efficacy was assessed by an increase in platelet count with confirmation at least 1 week apart. Responses were classified as complete (CR, 〉 150K/μL), partial (PR, 50-150K/μL), or minor (MR, 30-50K/μL). Adverse events and safety laboratories were evaluated using NCI CTC v3 toxicity grades. Other evaluations included circulating B-cell levels (CD19), veltuzumab serum levels, and human anti-veltuzumab antibody (HAHA) titers. Results The study has enrolled 25 patients (7M/18F, 21-92 years old, 5 post-splenectomy) with 7 receiving 2 IV veltuzumab doses at 80 (N=3), 120 (N=3), or 200 mg (N=1), and 10 receiving 2 SC doses at 80 (N=3), 160 (N=4), or 320 mg (N=3) during the completed Phase I portion of the study. The Phase II portion is now underway with 8 additional patients having received 2 SC veltuzumab doses at 320 mg. The 25 patients had a median duration of ITP of 1.8 years (range 0.2 - 20) with previous treatments including steroids (N=24), IVIG/anti-D (N=15), azathioprine/danazol (N=7), rituximab (N=5), TPO-R agonists (N=3) and vincristine/Doxil (N=2). One patient had a Grade 3 infusion reaction after receiving ∼100 mg veltuzumab at first IV dose. Otherwise veltuzumab was well tolerated with a limited number of Grade 1 infusion/injection reactions and no other safety issues. B cells were depleted rapidly with both IV and SC dosing with recovery times yet to be determined. At 80 and 120 mg x 2, IV veltuzumab achieved expected serum levels (mean Cmax 20.3 and 46.0 μg/mL, respectively) with a mean serum half-life of ∼1 week after last dose. SC veltuzumab had slower release over several days with lower serum levels, but comparable availability/exposure. Two patients developed low-level HAHA titers of uncertain clinical significance. Of 21 patients now with post-treatment response assessments, 13 (62%) achieved an objective response (CR+PR+MR), including 6 (29%) CRs. Responses, including CRs, occurred with both SC and IV administrations, and across all dose levels, with the highest OR (CR) rate of 100% (60%) seen in patients with more recently diagnosed ITP (≤1 year), albeit in small numbers of patients (N=5). Of 6 CRs, 5 are still continuing with a current median duration of response of 9 months (2.5 - 15 mo.) Conclusions Low-dose veltuzumab (2 doses, 2 weeks apart) demonstrates promising activity in relapsed ITP, including durable complete responses. Compared to IV infusions, subcutaneous injections offer practical benefits to both patients and the healthcare system, and the study is continuing to provide additional/confirmatory data for further clinical development of SC veltuzumab in ITP. Disclosures Saleh: Immunomedics: Research Funding. Off Label Use: veltuzumab, an investigational anti-CD20 antibody in clinical studies. Liebman:Immunomedics: Research Funding. Bernstein:Immunomedics: Research Funding. Negrea:Immunomedics: Research Funding. Bussel:Immunomedics: Research Funding. Onyegbula:Immunomedics: Research Funding. Farber:Immunomedics: Research Funding. Abassi:Immunomedics: Research Funding. Cosgriff:Immunomedics: Research Funding. Pennington:Immunomedics: Research Funding. Horne:Immunomedics: Employment. Teoh:Immunomedics: Employment. Gomaa:Immunomedics: Employment. Wegener:Immunomedics: Employment. Goldenberg:Immunomedics: Employment, Equity Ownership.

Abstract: To repurpose therapeutics for fibrolamellar carcinoma (FLC), we developed and validated patient-derived xenografts (PDX) from surgical resections. Most agents used clinically and inhibitors of oncogenes overexpressed in FLC showed little efficacy on PDX. A high-throughput functional drug screen found primary and metastatic FLC were vulnerable to clinically available inhibitors of TOPO1 and HDAC and to napabucasin. Napabucasin's efficacy was mediated through reactive oxygen species and inhibition of translation initiation, and specific inhibition of eIF4A was effective. The sensitivity of each PDX line inversely correlated with expression of the antiapoptotic protein Bcl-xL, and inhibition of Bcl-xL synergized with other drugs. Screening directly on cells dissociated from patient resections validated these results. This demonstrates that a direct functional screen on patient tumors provides therapeutically informative data within a clinically useful time frame. Identifying these novel therapeutic targets and combination therapies is an urgent need, as effective therapeutics for FLC are currently unavailable. Significance: Therapeutics informed by genomics have not yielded effective therapies for FLC. A functional screen identified TOPO1, HDAC inhibitors, and napabucasin as efficacious and synergistic with inhibition of Bcl-xL. Validation on cells dissociated directly from patient tumors demonstrates the ability for functional precision medicine in a solid tumor. This article is highlighted in the In This Issue feature, p. 2355

Abstract: Background: FL comprises one quarter of lymphoma in the United States, presents in a heterogeneous fashion, and generates substantial debate regarding optimal management strategies. The recently published clinical prognostic index (FLIPI, BLOOD104:1258) facilitates outcome evaluation and may guide therapeutic strategy. The National LymphoCare Study (NLCS) is an ongoing disease-based longitudinal observational study designed to assess patterns of initial disease presentation including prognosis, long term treatment choices, and clinical outcomes in FL patients. Methods: Beginning March, 2004, pts were recruited from U.S. community practices and academic centers. Pts with FL diagnosed within 6 months with no prior lymphoma history are eligible for enrollment. Collected data includes histology, staging and prognostic evaluation, serial management strategies including drug choices but not doses, response to treatment, and events including relapses and death. There is no study-specific prescribed treatment regimen or intervention. The treating physician determines management for FL according to clinical judgment. Results: 992 pts were enrolled from 207 sites through April, 2005. 182 community sites enrolled 86% of subjects. Pt characteristics include median age 62y, 52.5% female, 90.6% Caucasian, 40% Gr1, 26% Gr2, 19% Gr3, 13% NOS, with highest determined Ann Arbor stage = 17% I, 15%II, 26% III, 33%IV, 8% Unk. The demographic characteristics are similar to pts in the national SEER registry (median age 64, 51% F, 91.3% Caucasian) but clinical characteristics are notable for a higher fraction of advanced stage disease. 686/992 (69%) patients had calculable FLIPI scores based on initial investigator workup. Of factors contributing to FLIPI scores, LDH was collected by investigators in 78% of pts. When correlated with age, geography, and academic/community sites, LDH collection rates differ with 90% in academic sites vs 76% in community sites (p = .0002). Distribution of FLIPI among 686 pts with complete scores are shown in Table1, and show remarkable consistency across grades. Summary: The NLCS is an ongoing study with a large and rapidly growing database combining clinical and treatment data and is the first database investigating initial workup, prognosis, and outcomes of pts in a predominantly community based U.S. population. FL pts enrolled in NLCS are similar to those in the SEER database, and should be widely generalizable to the US population. FLIPI continues to define three distinct groups in the NLCS and is independent of histologic grade. Current evaluation patterns result in 31% incomplete FLIPI scores, suggesting this useful prognostic index is underutilized. FLIPI distribution (%) Low 36 37 37 38 34 81 14 Intermed 37 31 32 28 37 14 40 High 27 32 31 34 29 5 46 Solal Celigny n=1795 NLCS n=686 NLCS Gr1 n=276 NLCS Gr2 n=188 NLCS Gr3 n=136 Stage I/II n=234 Stage III/IV n=452

Abstract: Introduction: Ublituximab (UTX) is a novel, chimeric monoclonal antibody (mAb) which targets a unique epitope on the CD20 antigen and has been glycoengineered to enhance affinity for all variants of FcγRIIIa receptors, demonstrating greater antibody-dependent cellular cytotoxicity (ADCC) activity than rituximab and ofatumumab, particularly against cells that express low CD20 levels. Two Phase I trials of single agent UTX in relapsed/refractory CLL reported significant response rates with rapid and sustained lymphocyte depletion and a manageable safety profile. Ibrutinib, a novel oral BTK inhibitor approved for patients with previously treated CLL and MCL, displays high single agent activity and has reported increased activity in combination with non-glycoengineered anti-CD20 mAbs. Herein we report safety and efficacy data on the first combination of ibrutinib with a glycoengineered anti-CD20 mAb, UTX, from an ongoing Phase 2 trial. Methods: Eligible patients have relapsed or refractory CLL/SLL or MCL with an ECOG PS ≤ 2. The study was designed to assess safety, tolerability, and early overall response rate, with an initial safety run-in period consisting of 6 patients followed by open enrollment. UTX (Cohorts of 600 and 900 mg for CLL and at 900 mg for MCL patients) is administered on Days 1, 8, and 15 in Cycle 1 followed by Day 1 of Cycles 2 - 6. Ibrutinib is started on Day 1 and continues daily at 420 mg and 560 mg for CLL and MCL patients respectively. Following Cycle 6, patients come off study but remain on ibrutinib. Primary endpoint for safety: Adverse Events and Dose Limiting Toxicities (DLT) during safety run-in. Phase II primary efficacy endpoint: ORR with an emphasis on early activity with response assessments by CT scan scheduled prior to cycles 3 and 6 only. Results: 40 patients (33 CLL/ 7 MCL) have been enrolled to date with enrollment continuing. 23 M/17 F, median age 72 yr (range 52-86), ECOG 0/1/2: 20/19/1, median prior Tx = 2 (range 1-6), 38% with ≥ 2 prior anti-CD20 therapies; prior purine analog = 43%; prior alkylating agent = 68%; and prior purine and alkylating agent = 43%. No DLTs were observed during the safety run-in. Gr 3/4 AE’s occurring in at least 5% of patients and at least possibly related to UTX and/or ibrutinib included: neutropenia, thrombocytopenia, diarrhea, rash, leukocytosis, and infusion related reaction. There were no Grade 3/4 adverse events reported in ≥ 10% of patients. Ibrutinib was dose reduced due to an AE in 2 patients (1 diarrhea, 1 rash) and discontinued in 2 patients due to ibrutinib related AE’s (diarrhea and rash). IRR’s were managed with infusion interruptions with no patient requiring an ublituximab dose reduction. As of July 2014, 24/40 patients are evaluable for response. Best response to treatment is as follows: TableTypePts (n)CR (n)PR (n)SD (n)ORR (%)CLL non 17p/11q10-9190%17p/11q817-100%Total CLL18116194%MCL632183% The one CLL patient who achieved stable disease had a 46% nodal reduction. UTX appears to control ibrutinib related lymphocytosis with more than half of the patients within normal range for ALC by first efficacy assessment. Conclusions: Data suggests ublituximab, a glycoengineered anti-CD20 mAb, in combination with ibrutinib is both well-tolerated and highly active in patients with relapsed or refractory CLL and MCL. ORR was 94% in patients with CLL (100% in patients with high risk CLL: 17p, 11q del with 1 CR), with responses attained rapidly (median TTR: 8 weeks). In MCL, 83% of patients achieved a response at first efficacy assessment, with 50% of patients achieving a CR by week 20. For most patients, responses improved by the second efficacy assessment. The addition of ublituximab appears to mitigate ibrutinib related lymphocytosis producing earlier clinical responses than historically seen with ibrutinib monotherapy. Efficacy and safety will be updated on all enrolled patients. Disclosures Sharman: TG Therapeutics: Research Funding; Gilead: Consultancy, Research Funding; Roche: Research Funding; Pharmacyclics: Research Funding; Celgene: Consultancy, Research Funding. Farber:Leukemia Lymphoma Society NJ Chapter: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Alexion: Stock ownership Other. Schreeder:TG Therapeutics, Inc.: Research Funding. Kolibaba:TG Therapeutics: Research Funding; Gilead: Research Funding; Glaxo Smithkline: Research Funding. Sportelli:TG Therapeutics: Employment, Equity Ownership. Miskin:TG Therapeutics, Inc.: Employment, Equity Ownership. Weiss:TG Therapeutics, Inc.: Employment, Equity Ownership. Greenwald:TG Therapeutics: Research Funding.

Abstract: Background Outcomes for patients with DLBCL have improved over the past decade, with the addition of rituximab to CHOP or CHOP-like multi-agent chemotherapy regimens improving the 3-year overall survival (OS) of patients by 10-16% compared to multi-agent chemotherapy alone (Coiffier 2002; Pfreundschuh 2010). However, patients with high-intermediate or high-risk disease have relatively poor outcomes with the standard RCHOP regimen (Ziepert 2010); in a recent prospective trial of intermediate- and high-risk DLBCL patients, complete response (CR) rate for RCHOP alone was 26% (Hainsworth 2011). Brentuximab vedotin (ADCETRIS®) is an antibody-drug conjugate comprising the antibody cAC10, specific for human CD30, covalently attached to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a protease-cleavable linker. Brentuximab vedotin has demonstrated compelling activity as a single agent in patients with relapsed or refractory DLBCL, even those with low CD30 expression (Bartlett 2013). This phase 2, randomized, open label study is designed to evaluate the antitumor activity and safety of brentuximab vedotin (1.2 or 1.8 mg/kg) when administered in combination with standard RCHOP chemotherapy (A+RCHOP) for the front-line treatment of patients with CD30-unselected high-intermediate/high-risk (standard IPI score 3–5 or age-adjusted IPI [aaIPI] score 2–3) DLBCL (ClinicalTrials.gov NCT01925612). Methods Patients were randomized to receive up to 6 cycles of either 1.2 or 1.8 mg/kg brentuximab vedotin administered IV on Day 1 of every 21-day cycle in combination with RCHOP; prednisone was administered orally on Days 1-5 of every 21-day cycle. Assessments included disease response per Cheson 2007, as evaluated by the investigator, surveillance of adverse events (AEs), physical examination findings, and laboratory testing. The primary endpoints for this study are the CR rate at the end of treatment (EOT) and the type, incidence, and severity of AEs. Key secondary endpoints include objective response rate (ORR), progression-free survival (PFS), and OS. Results At the time of the planned interim analysis, 33 patients were enrolled (17 patients, 1.2 mg/kg A+RCHOP; 16 patients, 1.8 mg/kg A+RCHOP). Median age for all patients was 66 years (range, 21 to 81). At baseline, 36% were high-risk (IPI 4-5, aaIPI 3) and 64% were high-intermediate risk (IPI 3, aaIPI 2). The majority of patients (73%) had Stage IV disease and 33% had an ECOG status of 2. At the time of interim analysis, a total of 12 patients (6 patients in each arm) had completed EOT. Across both dose levels, ORR was 92% (11/12), with 7 CRs (58%), 4 PRs (33%), and 1 PD. The patient with PD subsequently died. Patients with PR had a median reduction of baseline tumor size of 84% (range, 92% to 83%), as measured by SPD. The only patient with follow-up after EOT converted from PR to CR without subsequent therapy. Treatment-emergent AEs occurring in ≥30% of patients treated (26/33) were nausea, diarrhea, peripheral sensory neuropathy, fatigue, and decreased appetite. Grade 3 or higher events occurring in more than 2 patients were febrile neutropenia and neutropenia. Events of peripheral neuropathy occurred equally per arm (46%, 1.2 mg/kg A+RCHOP; 46% 1.8 mg/kg A+RCHOP) and were generally Grade 1 or 2 (15% and 23%, respectively); events were of similar grade across dose levels. The median time to onset of any grade of peripheral neuropathy was 6 weeks (range, 2 to 10 weeks). Five patients (19%) had dose reductions due to peripheral neuropathy and 3 patients (12%) had dose reductions due to febrile neutropenia. One patient who received 1.2 mg/kg A+RCHOP discontinued study drug due to an AE (thrombocytopenia). Conclusions At doses of 1.2 or 1.8 mg/kg, A+RCHOP exhibited manageable toxicity in the treatment of newly-diagnosed DLBCL; the incidence of peripheral neuropathy was similar to single-agent administration of brentuximab vedotin (Pro 2012, Younes 2012) and RCHOP alone (Rummel 2013, Flinn 2014). In 12 patients with response-assessable, high-intermediate and high-risk DLBCL, A+RCHOP showed encouraging antitumor activity, with an ORR of 92% and a CR rate of 58%. Disclosures Yasenchak: Seattle Genetics, Inc.: Research Funding. Off Label Use: Brentuximab vedotin is indicated in the US for treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates and for the treatment of patients with systemic anaplastic large cell lymphoma after failure of at least one prior multi-agent chemotherapy regimen. . Farber:Seattle Genetics, Inc.: Research Funding. Budde:Seattle Genetics, Inc.: Research Funding. Ansell:Seattle Genetics, Inc.: Research Funding. Advani:Takeda Pharmaceuticals International Co.: Research Funding; Celgene: Research Funding; Pharmacyclics: Research Funding; Jansseen Pharmaceuticals: Research Funding; Genentech: Research Funding; Seattle Genetics, Inc.: Research Funding, Travel expenses Other. Holkova:Seattle Genetics, Inc.: Research Funding. Halwani:Seattle Genetics, Inc.: Research Funding. Knapp:Takeda Pharmaceuticals International Co.: Research Funding; EMD Serono: Research Funding; Bristol Myers Squibb: Research Funding; Celgene: Research Funding; Merck: Research Funding; Heron Pharmaceuticals: Research Funding, Travel expenses, Travel expenses Other; Genentech: Research Funding, Travel expenses, Travel expenses Other; Seattle Genetics, Inc.: Research Funding; Pharmacyclics: Research Funding. Fayad:Seattle Genetics, Inc.: Consultancy, Research Funding. Kolibaba:Genentech: Research Funding; Takeda Pharmaceuticals International Co.: Research Funding; Seattle Genetics, Inc.: Research Funding. Patel-Donnelly:Seattle Genetics, Inc.: Research Funding. Seetharam:Seattle Genetics, Inc.: Research Funding. Manley:Seattle Genetics, Inc.: Employment, Equity Ownership. Bartlett:Genentech: Research Funding; ImaginAb: Research Funding; Celgene: Research Funding; MedImmune: Research Funding; Novartis: Research Funding; Pharmacyclics: Research Funding; Pfizer: Research Funding; Takeda Pharmaceuticals International Co.: Research Funding; Seattle Genetics, Inc.: Research Funding, Travel expenses Other; Janssen: Research Funding; Astra Zeneca: Research Funding.

Abstract: This phase 1/2 study evaluated the safety, pharmacokinetic behavior and anti‐tumour activity of ublituximab, a unique type I, chimeric, glycoengineered anti‐ CD 20 monoclonal antibody, in rituximab‐relapsed or ‐refractory patients with B‐cell non‐Hodgkin lymphoma (B‐ NHL ) or chronic lymphocytic leukaemia ( CLL ). Induction therapy (doses of 450–1200 mg) consisted of 4 weekly infusions in cycle 1 for NHL and 3 weekly infusions in cycles 1 and 2 for CLL . Patients received ublituximab maintenance monthly during cycles 3–5, then once every 3 months for up to 2 years. Enrolled patients with B‐ NHL ( n  = 27) and CLL ( n  = 8) had a median of 3 prior therapies. No dose‐limiting toxicities or unexpected adverse events ( AE s) occurred. The most common AE s were infusion‐related reactions (40%; grade 3/4, 0%); fatigue (37%; grade 3/4, 3%); pyrexia (29%; grade 3/4, 0%); and diarrhoea (26%; grade 3/4, 0%). Common haematological AE s were neutropenia (14%; grade 3/4, 14%) and anaemia (11%; grade 3/4, 6%). The overall response rate for evaluable patients ( n  = 31) was 45% (13% complete responses, 32% partial responses). Median duration of response and progression‐free survival were 9·2 months and 7·7 months, respectively. Ublituximab was well‐tolerated and efficacious in a heterogeneous and highly rituximab‐pre‐treated patient population.

Abstract: Abstract 2085 Introduction. Although advanced patient age is commonly used as a factor in selecting therapy for patients with chronic lymphocytic leukemia (CLL), based on presumed associations with functional status, limited data exist regarding the relationships between age and physical, emotional, social, and functional well being. We examined the relationships between age and these domains of health-related quality of life (HRQOL) for CLL patients treated in US community practices. Methods. Baseline data were collected as part of Connect CLL®, a prospective observational registry initiated in March 2010 involving centers in the US. Data on patient demographics and clinical characteristics were provided by clinicians. HRQOL was self-reported by patients in the clinic at enrollment. Patients completed 3 psychometrically validated instruments: the Brief Fatigue Inventory (BFI), EQ-5D, and Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu). Standard analyses were conducted of each instrument given clinical characteristics at that time. Reported mean BFI, EQ-5D and FACT-Leu scores were analyzed by age group ( 〈 65, 65–74, 〉 74). Statistical significance of score differences among sub-cohorts was ascertained by ANOVA using SAS 9.1. Results. Baseline HRQOL data were reported by 604 patients, enrolled from 161 centers. Patients were predominantly male (62%) and white (90%) with mean age at 69.9 (standard deviation [SD] 11.2) yrs. HRQOL scores by age group are presented: There were no significant differences between the age groups in fatigue as measured by the BFI, or differences in overall HRQOL as measured by the EQ-5D Visual Analogue Scale (VAS) or the FACT-G. Anxiety/depression and self care are EQ-5D domains that also did not vary by age. Although mobility was most impaired in the oldest age group compared to the two younger groups, usual activities and pain/discomfort were worse in both the younger and older cohorts compared to those 65–74 years of age. FACT-Leu results indicated that the social/family domain scores did not vary by age, but that physical, emotional, and functional domains did vary statistically with the oldest typically doing better than the 65–74 year olds, but not necessarily better than those 〈 65. Conclusions. Initial results from the Connect CLL® Registry indicate that HRQOL does not worsen monotonically with older age. In this cohort, both the youngest and oldest age groups had worse HRQOL in certain domains, presenting an inverted v-shaped relationship. Future analyses should be conducted on: (1) how HRQOL may be affected over time with changes in disease; and, (2) how HRQOL may be influenced by alternative therapies. Results reported here should serve as a useful baseline reference. Disclosures: Pashos: Celgene: Membership on an entity's Board of Directors or advisory committees. Flowers:Genentech/Roche (unpaid): Consultancy; Celgene: Consultancy; Millennium/Takeda: Research Funding; Wyeth: Research Funding; Novartis: Research Funding. Weiss:Celgene: Membership on an entity's Board of Directors or advisory committees. Lamanna:Celgene: Membership on an entity's Board of Directors or advisory committees. Farber:Celgene: Membership on an entity's Board of Directors or advisory committees. Kipps:Igenica: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Research Funding; Abbot Industries: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; GSK: Research Funding; Gilead Sciences: Consultancy, Research Funding; Amgen: Research Funding. Lerner:Celgene: Membership on an entity's Board of Directors or advisory committees. Kay:Celgene: Membership on an entity's Board of Directors or advisory committees. Sharman:Celgene: Membership on an entity's Board of Directors or advisory committees. Grinblatt:Celgene: Membership on an entity's Board of Directors or advisory committees. Flinn:Celgene: Membership on an entity's Board of Directors or advisory committees. Kozloff:Celgene: Membership on an entity's Board of Directors or advisory committees. Swern:Celgene Corporation: Employment, Equity Ownership. Kahn:Celgene Corporation: Employment, Equity Ownership. Street:Celgene: Employment, Equity Ownership. Sullivan:Celgene: Employment, Equity Ownership. Keating:Celgene: Membership on an entity's Board of Directors or advisory committees.