Citations

Abstract High‐dimensional mass cytometry data potentially enable a comprehensive characterization of immune cells. In order to positively affect clinical trials and translational clinical research, this advanced technology needs to demonstrate a high reproducibility of results across multiple sites for both peripheral blood mononuclear cells (PBMC) and whole blood preparations. A dry 30‐marker broad immunophenotyping panel and customized automated analysis software were recently engineered and are commercially available as the Fluidigm® Maxpar® Direct™ Immune Profiling Assay™. In this study, seven sites received whole blood and six sites received PBMC samples from single donors over a 2‐week interval. Each site labeled replicate samples and acquired data on Helios™ instruments using an assay‐specific acquisition template. All acquired sample files were then automatically analyzed by Maxpar Pathsetter™ software. A cleanup step eliminated debris, dead cells, aggregates, and normalization beads. The second step automatically enumerated 37 immune cell populations and performed label intensity assessments on all 30 markers. The inter‐site reproducibility of the 37 quantified cell populations had consistent population frequencies, with an average %CV of 14.4% for whole blood and 17.7% for PBMC. The dry reagent coupled with automated data analysis is not only convenient but also provides a high degree of reproducibility within and among multiple test sites resulting in a comprehensive yet practical solution for deep immune phenotyping.

Catheter ablation has brought major advances in the management of patients with atrial fibrillation (AF). As evidenced by multiple randomized trials, AF catheter ablation can reduce the risk of recurrent AF and improve quality of life. In some studies, AF ablation significantly reduced cardiovascular hospitalizations. Despite the existing data on AF catheter ablation, numerous knowledge gaps remain concerning this intervention. This report is based on a recent virtual workshop convened by the National Heart, Lung, and Blood Institute to identify key research opportunities in AF ablation. We outline knowledge gaps related to emerging technologies, the relationship between cardiac structure and function and the success of AF ablation in patient subgroups in whom clinical benefit from ablation varies, and potential platforms to advance clinical research in this area. This report also considers the potential value and challenges of a sham ablation randomized trial. Prioritized research opportunities are identified and highlighted to empower relevant stakeholders to collaborate in designing and conducting effective, cost-efficient, and transformative research to optimize the use and outcomes of AF ablation.

AbstractImportanceIt is critical to develop a better understanding of the strategies provider organizations use to improve the performance of frontline clinicians and whether ACO participation is associated with differential adoption of these tools.ObjectivesCharacterize the strategies that physician practices use to improve clinician performance and determine their association with ACOs and other payment reforms.Data SourcesThe National Survey of Healthcare Organizations and the National Survey of ACOs fielded 2017‐2018 (response rates = 47 percent and 48 percent).Study DesignDescriptive analysis for practices participating and not participating in ACOs among 2190 physician practice respondents. Linear regressions to examine characteristics associated with counts of performance domains for which a practice used data for feedback, quality improvement, or physician compensation as dependent variables. Logistic and fractional regression to examine characteristics associated with use of peer comparison and shares of primary care and specialist compensation accounted for by performance bonuses, respectively.Principal FindingsACO‐affiliated practices feed back clinician‐level information and use it for quality improvement and compensation on more performance domains than non‐ACO‐affiliated practices. Performance measures contribute little to physician compensation irrespective of ACO participation.ConclusionACO‐affiliated practices are using more performance improvement strategies than other practices, but base only a small fraction of compensation on quality or cost.

Abstract Background: Anaplastic large cell lymphoma (ALCL) of the breast is a recently described clinicopathologic entity, almost always associated with breast implants, and does not overexpress the anaplastic lymphoma kinase (ALK) protein. Using the two largest US cancer databases, we describe its incidence, patterns of care, and clinical outcome. Methods: Incidence rate was calculated using 2000-2011 data from the Surveillance, Epidemiology, and End Results (SEER) Program and age-adjusted to the US 2000 standard population. For patient level data, we used the National Cancer Data Base (NCDB) Participant User File. We included all adult patients diagnosed from 1998-2011 with ALCL (ICD-O-3: 99714) who had breast as the primary site. Results: The incidence of breast ALCL was 0.001 per million. We identified 61 cases from NCDB. All of the patients were females and they were predominantly White (88.5%). The median age at diagnosis was 64 years (range, 18-90). The stage distribution was I (45.9%), II (21.3%), III (0%), IV (9.8%), and unknown (21.3%). The pattern of initial treatment was surgery alone (13.1%), chemotherapy alone (32.7%), chemotherapy and radiation (19.7%), surgery and chemotherapy (4.9%), surgery and radiation (4.9%), and tri-modality treatment (13.1%). In 7 patients (11.5%), no treatment was given. Two patients (1.6%) received stem cell transplant (1 autologous, 1 allogeneic) as part of initial treatment, one after chemotherapy and another one after surgery and chemotherapy. Overall survival data was available for patients diagnosed in 1998-2006 (29 patients). The median overall survival was 149.8 months (range, 2.6-157.9). Conclusions: ALCL of the breast is very rare. It presents mainly as early stage disease with very good prognosis. The patterns of care varied, although most patients received chemotherapy as part of the initial treatment. Table 1. Treatment type received Frequency Percent Cumulative Frequency Cumulative Percent Chemo only 20 32.79 20 32.79 Surgery only 8 13.11 28 45.90 Chemo, Radiation, No surgery 12 19.67 40 65.57 Chemo, Surgery, No radiation 3 4.92 43 70.49 Radiation, Surgery, No Chemo 3 4.92 46 75.41 All three combined 8 13.11 54 88.52 Nothing 7 11.48 61 100.00 Disclosures Parsons: Celgene: Speakers Bureau.

Introduction: Myelodysplastic syndromes (MDS) are a heterogenous group of blood disorders defined by peripheral cytopenia(s), bone marrow failure, morphological dysplasia, and risk of progression. To understand the genetic, epigenetic and biological factors associated with the initiation and progression of MDS, NHLBI created the National MDS Study (NCT02775383). This is a prospective cohort study conducted at 92 community hospitals and 29 academic centers enrolling patients undergoing diagnostic work up for suspected MDS or MDS/myeloproliferative neoplasm (MPN) overlap syndrome. Eligible patients have yet to receive any therapy directed at their cytopenias. Previously untreated cytopenic participants underwent centralized histopathology and data review at the time of enrollment for assignment into distinct subcategories: MDS, MDS/MPN overlap, AML, and Other. Targeted exon sequencing of 96 genes was performed using marrow specimens from the first 300 consecutive individuals in the study. Here we report the genetic mutations for this cohort. Methods: NovaSeq 6000 was used for deep sequencing at a mean coverage of 1,286X and mean breadth (bases covered at ≥100X) of 99.8%. Reads were aligned against build GRCh38 using BWA-MEM, and VarScan2 was used to detect SNVs and INDELS. Variants were filtered for those with an allele base quality of >25 in combination with rule-based and manual review criteria. Subjects in the Other category without an identified malignancy were considered clonal cytopenias of undetermined significance (CCUS) when a mutation or a clonal cytogenetic change was present. Fisher's exact and Wilcoxon rank sum tests in combination with Bonferroni correction were applied to compare groups. Results : A total of 350 putative nonsynonymous pathogenic variants in 36 genes with an allele frequency of >.05 were identified across 150 patients (50%). At least one variant was noted in the following proportion of individuals: 61/72 (85%) with MDS, 13/13 (100%) with MDS/MPN, 15/17 (88%) with AML, and 61/198 (31%) in the Other category, of which 48 were CCUS and 13 were other cancers. Two CCUS patients only had a cytogenetic abnormality. Table 1 shows the distribution of variants in each subcategory of patients for the most commonly mutated genes in our cohort of 300 subjects. Mutations in these genes were enriched in specific groups: SF3B1, STAG2,TP53, and ASXL1 in MDS; TET2 in MDS/MPN; and IDH2 and TP53 in AML (one-sided p<0.0012). None were enriched in the Other group. Within the CCUS subset, 21 genes were mutated, with 37 of 50 (74%) patients having a mutation in TET2, ASXL1, SRSF2, SF3B1, or DNMT3A. The heatmap presented in Figure 1 summarizes variants by subject and allele frequency. Pair-wise comparisons of baseline characteristics of subjects between MDS, MDS/MPN, AML, or CCUS groups revealed no significant differences for age or sex. The CCUS group had significantly higher hemoglobins than the MDS group with median hemoglobin levels of 11.35 and 9.40 g/dL, respectively (p<0.0084). AML had significantly lower platelets compared to all other groups (median of 53 vs. > 110x109/L , respectively, p<0.0084). All groups significantly differed in their median ANC with AML having the lowest (0.8x109/L), followed by MDS (1.5x109/L), CCUS (2.45x109/L), and MDS/MPN overlap (5.95x109/L) (p<0.0084). There was no difference in the median number of variants per patient between groups or correlation with age (rs=0.11, p=0.18). The maximum variant allele frequency (maxVAF) per patient was highest in the MDS/MPN group (median = 0.42, range = 0.38-0.91) and lowest in the CCUS group (median = 0.37, range =0.06-0.98) with the MDS/MPN group having a significantly higher maxVAF compared to the MDS and the CCUS groups (p<0.0084). The proportions of subjects with mutations was similar for those who had abnormal (92% [34/37]) and normal (91% [80/88]) cytogenetics. Conclusions: Incorporation of gene-panel sequencing in the comprehensive evaluation of 300 adult cytopenic patients identified half of the cohort with potentially pathogenic variants. Ultimately, a diagnosis of CCUS was possible in 48 of 183 subjects (26%) not diagnosed with MDS, MDS/MPN overlap syndrome, AML, other cancers or clonal cytogenetics. This study continues to serially bank samples from patients with CCUS, in addition to MDS, MDS/MPN, and ICUS, with the goal to better understand the natural history of these diseases and their progression. Disclosures Lindsley: Jazz Pharmaceuticals: Research Funding; Takeda Pharmaceuticals: Consultancy; Medlmmune: Research Funding. Bejar:Celgene: Consultancy; Takeda Pharmaceuticals: Research Funding; AbbVie/Genentech: Consultancy, Honoraria; Astex/Otsuka: Consultancy; Modus Outcomes: Consultancy; Daiichi-Sankyo: Consultancy. Al Baghdadi:Celgene: Consultancy, Honoraria; Heron: Consultancy, Honoraria; Tracon: Equity Ownership; Epizyme: Equity Ownership; Bristol Myer Squibb: Consultancy, Honoraria; Sunesis: Equity Ownership; Portola: Equity Ownership; Heron therapeutics: Equity Ownership; Cardinal health: Consultancy, Honoraria; Bristol Myer Squibb: Equity Ownership; Celgene: Equity Ownership; Spectrum pharmaceutical: Equity Ownership; Astrazeneca: Equity Ownership; Seattle genetics: Equity Ownership; Roche: Consultancy, Honoraria. DeZern:Astex Pharmaceuticals, Inc.: Consultancy; Celgene: Consultancy. Foran:Agios: Honoraria, Research Funding. Gore:Celgene Corporation: Consultancy, Research Funding. Komrokji:DSI: Consultancy; Agios: Consultancy; Novartis: Speakers Bureau; JAZZ: Speakers Bureau; pfizer: Consultancy; celgene: Consultancy; Incyte: Consultancy; JAZZ: Consultancy. Maciejewski:Alexion: Consultancy; Novartis: Consultancy. Starczynowski:Kurome Therapeutics: Consultancy. Sekeres:Millenium: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.

Introduction: Globin gene sequencing has long been impeded by repetitive regions, homology and structural variation. Currently, long-read sequencing technology has been limited by high cost and error rate. These challenges can be mitigated by sample multiplexing of targeted capture sequencing and the use of consensus reads, respectively. This ongoing study analyzes the utility of long range sequencing technology in identifying historically problematic beta globin cluster mutations. Materials and methods: Long range sequencing was performed on complex beta globin gene cluster cases utilizing the Sequel platform (Pacific Biosciences, Menlo Park, California, United States). Sample input was 1 microgram of DNA extracted from whole blood. Circular Consensus Sequence (CCS) FASTQ sequences files were mapped to reference genome (GRCh37/hg19) using NGMLR, followed by annotation of variants using a custom bioinformatics workflow. Comparison to multiplex ligation-dependent probe amplification (MLPA), Sanger sequencing, array CGH, short-range NGS (300 bp), hemoglobin protein, and clinical data was performed. Results: CCS read length varied from 1 to 10 kb, average 3.5. Analysis of the beta globin cluster region showed impressive superiority and comprehensiveness to Sanger, MLPA, array CGH and short range sequencing technology: 1) single nucleotide variants (SNVs) were identified to a sensitivity and specificity of 99.5%; 2) large structural variants (SVs) such as large deletions, duplications, insertions, crossovers and fusions spanning many kilobases were characterized in the heterozygous, homozygous and compound heterozygous state to a precise genomic coordinate (table 1); 3) phasing SNVs identified Hb S haplotypes (Central African region (CAR), Benin, Senegal, Arab-Indian and Cameroon). Conclusion: 1) Long range sequencing holds significant promise in genotyping hemoglobin disorders. This method improves efficiency with potential for a single test offering with increased resolution, particularly in large deletion analysis. Complex cases greatly benefited from improved range and resolution. 2) The decreased requirement of blood volume for extensive testing is of particular interest for the pediatric population. 3) Genotyping of Hb S patients detected by positive newborn screening will help predict need for prophylaxis or therapy by assessing variant zygosity, phasing and haplotypes. In conclusion, we believe that long range sequencing has immense potential to contribute extensively to thalassemia and hemoglobinopathy diagnostics and is far superior to the currently available technologies for beta globin cluster analysis. Disclosures Jen: Celgene: Employment.

Background: Despite treatment advances, multiple myeloma (MM) remains a condition with high unmet medical need as patients (pts) relapse and become resistant to therapy. MM pts experience a range of serious disease-related symptoms and side effects impacting their functioning and health-related quality of life (HRQL). The median overall survival (OS) has improved with the advent of new treatments in the last two decades, however, the impact of newer combination treatments on pt quality of life remains unknown (Beckner, N et al. Cancer Res. 2011;183:25; Bharat, N et al. J Clin Oncol 2019;37:15(suppl):8039). Venetoclax is a novel, orally bioavailable small molecule inhibitor of BCL-2 activity in MM. In the Phase 3 double-blind, randomized clinical trial (M14-031, BELLINI) progression free survival (PFS) was studied in relapsed/refractory (RR) MM pts receiving venetoclax or placebo in combination with bortezomib and dexamethasone. In addition, patient-reported outcomes (PRO) data focused on physical functioning, pain, and fatigue from BELLINI were evaluated to better understand the overall impact on pt HRQL of adding venetoclax to bortezomib and dexamethasone-based doublet therapy. Methods: The BELLINI Phase 3 study (NCT01794520) enrolled patients ≥18 y old with R/R MM who had received 1-3 prior lines of therapy. The study met its primary endpoint of PFS (HR 0.63, 95% CI=0.44-0.89) but higher risk of death (HR 2.027, 95% CI=1.04-3.95) was observed in the treatment arm compared with placebo, although the OS data are not yet mature (Kumar, S et al. EHA Library. Jun 16 2019;273254:LB2601). The secondary HRQL endpoints included in this study were pain severity, fatigue, physical functioning (PF), and global health status, which were measured using the Brief Pain Inventory-Short Form (BPI-SF), PROMIS Fatigue Short Form surveys, and the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Change from baseline to day 1 of each cycle visit (up to 25 cycles or last treatment visit) was assessed for each measure in both the treatment and placebo groups. Summary analyses compared mean and median scores between arms at each cycle. The treatment effect was evaluated in a mixed effect model controlling for the patient's baseline score, total visits (or cycles of treatment), age (<65 or ≥65), prior therapy lines, and prior proteasome inhibitor exposure. The model also included an interaction term examining treatment by visits. Results: The intention-to-treat (ITT) dataset included 194 pts (median age: 66y; 53% with 2 or 3 prior lines of therapy) in the treatment group and 97 pts (median age: 65y; 55% with 2 or 3 prior lines of therapy) in the placebo group (2:1 randomization). There was no clear evidence for an independent effect of treatment on PF (P=0.522). Pain scores across multiple measures showed a similar trend, with a statistically non-significant improvement of unadjusted average "Worst Pain" scores for the venetoclax group (P=0.289; Figure B). Non-inferiority in pain results were replicated by the pain subscale of the QLQ-30 (P=0.778), the BPI pain severity index (P=0.418), and the related BPI pain interference subscale score (P=0.603). Fatigue scores likewise demonstrated no significant differences between treatment arms whether using PROMIS Cancer Fatigue t-scores (P=0.442), raw scores (P=0.568), or the 3-item QLQ-C30 subscale (P=0.959), although there was a positive trend across cycle summary scores for the treatment group compared with the placebo group. Unadjusted QLQ-C30 PF subscale scores showed declines from baseline that were generally worse in the placebo group across 25 treatment cycles, although differences were smaller and non-significant in the adjusted model (Figure A). Conclusions: Comparable HRQL in pain severity, fatigue, and PF was observed in RRMM pts receiving venetoclax in combination with bortezomib and dexamethasone compared to pts receiving bortezomib and dexamethasone. The summary scores showed outcomes that were comparable or slightly improved for those randomized to the venetoclax combination. Results of concurrent measures of the same or associated concepts reinforced confidence in these results. Additional analyses of subgroups are ongoing (eg, t(11;14), BCL-2 expression status) and may provide further insights surrounding HRQL in these populations. Figure Disclosures Gasparetto: BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Popat:Takeda: Honoraria, Other: travel, accommodations, expenses; GSK: Consultancy, Honoraria; Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel, accommodations, expenses; Janssen: Honoraria, Other: travel support to meetings; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Kumar:Celgene: Consultancy, Research Funding; Takeda: Research Funding; Janssen: Consultancy, Research Funding. Cavo:celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; AbbVie: Consultancy, 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, Speakers Bureau; amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; novartis: Honoraria; sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; bms: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. de la Rubia:Janssen: Consultancy; AbbVie: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Takeda: Consultancy. Hungria:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, 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, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Speakers Bureau; Celgene: 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; Celgene: 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. Salwender:Sanofi: Honoraria, Other: Travel or accommodations; Amgen: Honoraria, Other: Travel or accommodations; Janssen Cilag: Honoraria, Other: Travel or accommodations; AbbVie: Honoraria; Bristol-Myers Squibb: Honoraria, Other: Travel or accommodations; Celgene: Honoraria, Other: Travel or accommodations; Takeda: Honoraria, Other: Travel or accommodations. Suzuki:Ono: Research Funding; BMS: Honoraria, Research Funding; Takeda: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Maciel:Amgen: Other: funding for travel, teaching, participation in advisory boards; Janssen: Other: funding for travel, teaching, participation in advisory boards. Moreau:Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Harrison:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: investigator on studies, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Jia:AbbVie: Employment, Other: Stock/stock options. Karve:AbbVie: Employment, Other: stock/stock options. Ma:Genentech: Employment, Other: stock options; AbbVie: Other: Alliance Partner. Devine:Genentech: Employment, Other: stock options; AbbVie: Other: Alliance Partner. Benjamin:AbbVie: Employment, Other: stock/stock options.

Background: Mantle Cell Lymphoma (MCL) is an aggressive form of Non Hodgkin Lymphoma (NHL) and typically presents in patients over the age of 60 years. Bendamustine and rituximab (BR) combination is one of the standard treatments for MCL and is given to patients for whom high dose chemotherapy with autologous stem cell rescue is planned in the first remission. Progression free survival (PFS) with BR is approximately 36 months (Rummel M Lancet 2013; Flinn IW Blood 2014) and the regimen is overall well tolerated. Venetoclax (VEN) is an orally available inhibitor of BCL2, an anti-apoptotic protein highly expressed in several NHL. Single agent activity has mostly been studied in a Phase I study (in various NHL histologies) where 28 MCL patients were enrolled. Overall response rate was 75% (21 of 28) but complete response (CR) rate was only 21% (6 of 28). Tumor lysis syndrome (TLS) has been associated with VEN and initial dosing requires a ramp up period (Davids MS JCO 2018). VEN has also been combined with other agents in MCL with promising activity (Tam CS NEJM 2018) VEN has been studied as a chemotherapy sensitizer and has shown pre-clinical synergy with chemotherapy. In Follicular lymphoma, BR+VEN was studied at 800mg PO continuous daily dosing and showed an excessive Grade 3-4 adverse event (AE) rate of 78% compared to historical studies of 46% (Zinzani ASH 2016). We hypothesize that, in MCL, VEN can be safely combined with BR at a lower dose and intermittent dosing with improvements to the response rate based on historical controls and maintain a better safety profile. Study Design: This Phase II single arm, multicenter study evaluates VEN at a max dose of 400mg with BR (Bendamustine 90mg/m2 IV day 1 and 2; rituximab 375mg/m2 IV or SQ equivalent day 1) for six 28-day cycles in untreated patients with MCL over the age of 60 years (NCT03834688). Cycle 1 will include a VEN dose titration over the 4 week course (20mg D1-7, 50mg D8-14, 100mg D15-21, and 200mg D22-28). For Cycles 2-6, VEN will be given at 400mg daily x 10 days starting with day 1. Participants are followed for 6 cycles, though will be followed for progression and survival afterward. Participants may receive maintenance rituximab at investigator's discretion. Eligible participants, age 60 years or older, must have biopsy proven untreated MCL with t(11;14) or cyclin D1 expression, though a short course of steroids is allowed for symptomatic MCL. They must have adequate organ function and not require any prohibited concomitant medications. Primary outcome is CR rate as assessed by the Lugano criteria. We estimate a historical CR rate of BR after induction of about 70%. A 15% increase in this rate, to 85% CR, is considered promising for the combination. To achieve this goal, the study will enroll 56 participants (53 eligible) to achieve a 90% power to detect the difference with a 10% Type I error rate. We will also evaluate PFS and overall survival. TLS is an AE of interest and will be evaluated after 19 participants have been enrolled and treated during cycle 1. Minimal residual disease (MRD) will be assessed throughout the study. MRD from peripheral blood will be compared to bone marrow aspirates in all participants undergoing bone marrow aspirate at the end of treatment. Tumor samples at screening and progression will be collected for future study. This study is conducted through PrECOG and is funded by Genentech, a member of the Roche Group. Venetoclax is co-developed by Genentech and AbbVie. The study is slated to open in Fall of 2019 at 10 US sites. Figure Disclosures Portell: AbbVie: Research Funding; Pharmacyclics: Consultancy; Janssen: Consultancy; Genentech: Consultancy, Research Funding; Amgen: Consultancy; Bayer: Consultancy; BeiGene: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; TG Therapeutics: Research Funding; Xencor: Research Funding; Roche/Genentech: Research Funding; Infinity: Research Funding. Bennani:Seattle Genetics: Other: Advisory board; Adicet Bio: Other: Advisory board; Kite Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Adicet Bio: Other: Advisory board; Purdue Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Adicet Bio: Other: Advisory board; Seattle Genetics: Other: Advisory board; Kite Pharma: Other: Advisory board; Kite Pharma: Other: Advisory board. Naik:Celgene: Other: Advisory board. Parsons:Celgene: Speakers Bureau; Amgen: Speakers Bureau. Kahl:BeiGene: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy; TG Therapeutics: Consultancy. OffLabel Disclosure: Venetoclax is not approved for use in MCL.

In recent years, work has been done to understand the mechanisms of Doppler ultrasound twinkling artifacts (TAs) and why they appear over kidney stones. In this work, twinkling artifacts were evaluated as a possible method of locating and characterizing kidney stones. Doppler ultrasound scanning was used to evaluate 47 stones of different types and sizes. An isolated stone study was used to understand the behavior of the TAs while varying transmit voltages. An ex vivo kidney study was conducted to determine if TAs were localized to the stones. An ex vivo randomized stone placement study was used to evaluate the robustness of detecting and locating stones. The TAs were also shown to be isolated to the stone when placed in an ex vivo kidney. The randomized stone placement study showed that this method could find all 47 used stones with only two false positives. A few limitations to this method were found with issues accurately sizing stones as well as difficulties in specificity for characterizing the stones. Further work will be done on these limitations by improving the Doppler acquisition and processing code as well as evaluating the use of TAs in human studies.

Local Phase Velocity Imaging (LPVI) is a novel method of shear wave elastography (SWE) analysis, which provides phase velocity images at multiple frequencies. The primary components of this method include using two acoustic radiation force (ARF) pushes near the edges of the field-of-view. Fourier analysis of the spatiotemporal data is conducted to obtain maps of the phase velocity at multiple frequencies. A robustness study was conducted to evaluate the effectiveness of LPVI in elastic and viscoelastic phantoms with different mechanical properties, ARF focal depths and F-numbers, and shear wave frequencies using a linear array transducer. The results showed effective phase velocity reconstructions for most scanning parameters in the phantoms evaluated. We evaluated mean and standard deviations of phase velocities in the different phantoms for regions-of-interest defined in the images. Issues were seen with shear wave signal being distorted from the incident push when using low F-numbers as well as issues with attenuating shear waves with higher F-numbers and deeper focal depths. Future directions of this work will be to evaluate the robustness of LPVI in inclusion phantoms as well as testing on a curved array transducer.