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TD-DFT calculations were performed on neutral TinO2n, TinO2n–1, and TinO2n–2clusters, where n≤ 7. Calculations show the TinO2nclusters are closed shell systems containing empty d orbitals and that the partially filled d orbitals of the suboxide clusters have a profound effect on their structural, electronic, and topological properties. The low energy photoexcitations of TinO2nclusters are all O-2p to Ti-3d transitions, while the open-shell suboxide clusters are all characterized by d–d transitions that occur at a much smaller optical gap. Upon low energy photoabsorption, the localization of the hole is accompanied by a local bond elongation, i.e., polaron formation, whereas d-electrons are generally delocalized around the cluster. The properties of the clusters, including the oxygen binding energies and structures, were calculated to account for the variation in relative populations found in experimental cluster distributions. Several TinO2n–2clusters contain higher symmetry which is reflected in their relative stability. In particular, the tetrahedral symmetry of Ti4O6inhibits charge carrier localization and therefore exhibits higher stability.

Background: Chimeric antigen receptor (CAR) T-cell therapy provides effective treatment for large B-cell lymphoma (LBCL). Cost-utility analyses examining and comparing the value of these treatments require health state utilities representing key characteristics to differentiate among therapies. This study estimated utilities for adverse events (AEs) associated with CAR T-cell therapy, including cytokine release syndrome (CRS) and neurological events (NEs). Methods: Health state vignettes were drafted based on literature review, AE reports from a trial of CAR T-cell therapy, and clinician input. Health states were valued in time trade-off interviews with general population participants in the UK. The first vignette described relapsed/refractory LBCL treated with CAR T-cell therapy without AEs. Five other vignettes had the same LBCL and treatment description, with the addition of an AE. Disutilities (i.e., utility decrease) associated with these AEs were calculated by subtracting the utility of the health state without AEs from those of the other health states. Results: Interviews were completed with 218 participants (50% male; mean age 49 years). Mean (standard deviation [SD]) utility for CAR T-cell therapy without AEs was 0.73 (0.30). Mean (SD) disutilities associated with CRS were −0.01 (0.04) for grade 1, −0.05 (0.09) for grade 2, and −0.23 (0.24) for grade 3/4. Mean (SD) disutilities associated with NEs were −0.04 (0.07) for grade 1/2 and −0.18 (0.22) for grade 3/4. Conclusions: More severe AEs were associated with greater disutilities. Health state utilities estimated in this study may be useful in cost-effectiveness models examining the value of CAR T-cell therapy in patients with LBCL.

Excited state lifetimes of neutral Cr2On(n< 5) clusters were measured using femtosecond pump–probe spectroscopy. Density functional theory calculations reveal that the excited state dynamics are correlated with changes in the cluster’s electronic structure with increasing oxidation. Upon absorption of a UV (400 nm) photon, the clusters exhibit features attributed to three separate relaxation processes. All clusters exhibit similar subpicosecond lifetimes, attributed to vibrational relaxation. However, the ∼30 fs transient signal fraction grows linearly with oxidation, matching the amount of O to Cr charge transfer character of the photoexcitation and highlighting a gradual transition between semiconducting and metallic behavior at the molecular level. A long-lived (>2.5 ps) response is recorded only in clusters with significant d-electron character, suggesting that adiabatic relaxation back to the ground state is efficient in heavily oxidized clusters, due to the presence of terminal O atoms. The simple picture of sequential oxidation of Cr2Onreveals a linear variation in the contributions of each relaxation component to the total transient signals, therefore opening possibilities for the design of new molecular spintronic materials.

CD19-directed chimeric antigen receptor (CAR) T-cell therapy has shown efficacy as a third-line or later treatment in patients with relapsed/refractory large B-cell lymphoma (LBCL). Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire, we evaluated the impact of CAR T-cell treatment with lisocabtagene maraleucel (liso-cel) on health-related quality of life (HRQoL) and symptoms in patients with relapsed/refractory LBCL in the ongoing, open-label, nonrandomized TRANSCEND NHL 001 trial. Clinically meaningful improvement was observed in EORTC QLQ-C30 scores for global health status/QoL, based on a minimally important difference of 10 points at 2 to 18 months after liso-cel infusion. There were no clinically meaningful changes in physical functioning and pain, whereas clinically meaningful improvements were observed in fatigue at 2, 12, and 18 months. The proportion of patients with clinically meaningful improvement in global health status/QoL was generally higher for treatment responders than for nonresponders. A trend toward decreased mean EQ-5D-5L index scores was observed at 1 month after liso-cel infusion, followed by subsequent increases through 18 months. Mean EQ-5D-5L visual analog scale scores increased from 2 through 18 months. In summary, patients with relapsed/refractory LBCL treated with liso-cel had early, sustained, and clinically meaningful improvements in HRQoL and symptoms that correlated with antitumor activity. This study was registered at www.clinicaltrials.gov as #NCT02631044.

CD19-directed chimeric antigen receptor (CAR) T-cell therapy has shown efficacy as a third-line or later treatment in patients with relapsed/refractory large B-cell lymphoma (LBCL). Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire, we evaluated the impact of CAR T-cell treatment with lisocabtagene maraleucel (liso-cel) on health-related quality of life (HRQoL) and symptoms in patients with relapsed/refractory LBCL in the ongoing, open-label, nonrandomized TRANSCEND NHL 001 trial. Clinically meaningful improvement was observed in EORTC QLQ-C30 scores for global health status/QoL, based on a minimally important difference of 10 points at 2 to 18 months after liso-cel infusion. There were no clinically meaningful changes in physical functioning and pain, whereas clinically meaningful improvements were observed in fatigue at 2, 12, and 18 months. The proportion of patients with clinically meaningful improvement in global health status/QoL was generally higher for treatment responders than for nonresponders. A trend toward decreased mean EQ-5D-5L index scores was observed at 1 month after liso-cel infusion, followed by subsequent increases through 18 months. Mean EQ-5D-5L visual analog scale scores increased from 2 through 18 months. In summary, patients with relapsed/refractory LBCL treated with liso-cel had early, sustained, and clinically meaningful improvements in HRQoL and symptoms that correlated with antitumor activity. This study was registered at www.clinicaltrials.govas #NCT02631044.

Chimeric antigen receptor (CAR) T-cell therapies have demonstrated high response rates in patients with relapsed/refractory large B-cell lymphoma (LBCL); however, these therapies are associated with 2 CAR T cell–specific potentially severe adverse events (AEs): cytokine release syndrome (CRS) and neurological events (NEs). This study estimated the management costs associated with CRS/NEs among patients with relapsed/refractory LBCL using data from the pivotal TRANSCEND NHL 001 trial of lisocabtagene maraleucel, an investigational CD19-directed defined composition CAR T-cell product with a 4-1BB costimulation domain administered at equal target doses of CD8+ and CD4+ CAR+ T cells. This retrospective analysis of patients from TRANSCEND with prospectively identified CRS and/or NE episodes examined relevant trial-observed health care resource utilization (HCRU) associated with toxicity management based on the severity of the event from the health care system perspective. Cost estimates for this analysis were taken from publicly available databases and published literature. Of 268 treated patients as of April 2019, 127 (47.4%) experienced all-grade CRS and/or NEs, which were predominantly grade ≤2 (77.2%). Median total AE management costs ranged from $1930 (grade 1 NE) to $177 343 (concurrent grade ≥3 CRS and NE). Key drivers of cost were facility expenses, including intensive care unit and other inpatient hospitalization lengths of stay. HCRU and costs were significantly greater among patients with grade ≥3 AEs (22.8%). Therefore, CAR T-cell therapies with a low incidence of severe CRS/NEs will likely reduce HCRU and costs associated with managing patients receiving CAR T-cell therapy. This clinical trial was registered at www.clinicaltrials.gov as #NCT02631044.

Chimeric antigen receptor (CAR) T-cell therapies have demonstrated high response rates in patients with relapsed/refractory large B-cell lymphoma (LBCL); however, these therapies are associated with 2 CAR T cell–specific potentially severe adverse events (AEs): cytokine release syndrome (CRS) and neurological events (NEs). This study estimated the management costs associated with CRS/NEs among patients with relapsed/refractory LBCL using data from the pivotal TRANSCEND NHL 001 trial of lisocabtagene maraleucel, an investigational CD19-directed defined composition CAR T-cell product with a 4-1BB costimulation domain administered at equal target doses of CD8+and CD4+CAR+T cells. This retrospective analysis of patients from TRANSCEND with prospectively identified CRS and/or NE episodes examined relevant trial-observed health care resource utilization (HCRU) associated with toxicity management based on the severity of the event from the health care system perspective. Cost estimates for this analysis were taken from publicly available databases and published literature. Of 268 treated patients as of April 2019, 127 (47.4%) experienced all-grade CRS and/or NEs, which were predominantly grade ≤2 (77.2%). Median total AE management costs ranged from $1930 (grade 1 NE) to $177 343 (concurrent grade ≥3 CRS and NE). Key drivers of cost were facility expenses, including intensive care unit and other inpatient hospitalization lengths of stay. HCRU and costs were significantly greater among patients with grade ≥3 AEs (22.8%). Therefore, CAR T-cell therapies with a low incidence of severe CRS/NEs will likely reduce HCRU and costs associated with managing patients receiving CAR T-cell therapy. This clinical trial was registered at www.clinicaltrials.govas #NCT02631044.

Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, chimeric antigen receptor (CAR) T-cell product. We aimed to assess the activity and safety of liso-cel in patients with relapsed or refractory large B-cell lymphomas.

The major concern of pancreatic islet transplantation is that the implanted islets are exposed to the immune system of the recipient. To overcome this challenge, the peptide amphiphile (PA) nanomatrix gel was used for immunoisolation of islets through microencapsulation. The PA can self-assemble to form a nanomatrix gel with an extracellular matrix-mimicking, islet nurturing microenvironment and a semipermeable immune barrier. In this study, the islet protective effect of the PA nanomatrix gel was evaluated by coculture of PA-encapsulated human islets with differentiated U937 cells (human monocyte cell-line) for 3 and 7 days. The coculture of the bare islets with the differentiated U937 cells stimulated proinflammatory cytokine (IL-1β and TNF-α) secretion and caused islet death after 7 days, which simulated an early inflammatory response environment after islet transplantation. The PA-encapsulated islets, however, did not stimulate proinflammatory cytokine secretion and maintained islet viability up to 7 days. More insulin-producing β cells were observed in PA-encapsulated islets compared to bare islet controls after exposure to differentiated U937 cells for 7 days compared to the bare islets. This result was confirmed by dithizone staining analysis. Further evaluation of islet functionality was assessed by a glucose-stimulated insulin secretion test. The PA-encapsulated islets showed greater insulin secretion response to glucose stimulation than the bare islets with the differentiated U937 cells after 3 and 7 days. These results demonstrated that islet encapsulation with the PA nanomatrix gel was able to improve islet survival and function in the presence of inflammatory responses, which will increase the success rate of islet engraftment and the efficacy of islet transplantation.

Human genetic factors are important determinants of malaria risk. We investigated associations between multiple candidate polymorphisms—many related to the structure or function of red blood cells—and risk for severe Plasmodium falciparummalaria and its specific phenotypes, including cerebral malaria, severe malaria anaemia, and respiratory distress.

The widespread distribution and relapsing nature of Plasmodium vivax infection present major challenges for the elimination of malaria. To characterize the genetic diversity of this parasite in individual infections and across the population, we performed deep genome sequencing of >200 clinical samples collected across the Asia-Pacific region and analyzed data on >300,000 SNPs and nine regions of the genome with large copy number variations. Individual infections showed complex patterns of genetic structure, with variation not only in the number of dominant clones but also in their level of relatedness and inbreeding. At the population level, we observed strong signals of recent evolutionary selection both in known drug resistance genes and at new loci, and these varied markedly between geographical locations. These findings demonstrate a dynamic landscape of local evolutionary adaptation in the parasite population and provide a foundation for genomic surveillance to guide effective strategies for control and elimination of P. vivax.

An excerpt from an interview conducted with agency managers who work with those customer service winners on the issue of 'how do agency managers find job candidates who possess these qualities'.

Introduction. Proximal tibia physeal fractures in children are not very common but can be dangerous because they can harm popliteal fossa structures, especially the popliteal artery. Popliteal artery injuries (PAI) are most commonly the result of trauma to the lower extremity, including blunt force, hyperextension injuries, complex fractures, and knee dislocations that can compromise popliteal neurovascular structures. Case Presentation. A 14-year-old boy presents to the emergency department after being transferred from an outside hospital 24 hours after a left lower extremity hyperextension injury. Radiographs demonstrated a Salter-Harris III proximal tibia fracture with posterior displacement. ABIs were deferred due to palpable distal pulses and no evidence of compartment syndrome. Closed reduction and percutaneous pinning were planned to correct the fracture. Intraoperatively, it was discovered that knee extension decreased lower extremity perfusion while knee flexion returned perfusion. An angiography revealed a popliteal artery occlusion with no distal flow. Based on this, an above-knee to below-knee popliteal bypass using the contralateral great saphenous vein was performed followed by closed reduction and percutaneous pinning of the proximal tibia. Conclusion. Proximal tibia physeal injuries, especially the Salter-Harris III and IV injuries, warrant a high index of suspicion of popliteal artery injuries. Palpable pulses and delayed presentation in the distal lower extremity do not rule out a PAI because collateral flow to the anterior and posterior tibial arteries may mask signs of an avascular limb, highlighting the need for a thorough history and physical exam. The authors present this case to reaffirm the importance of an ankle-brachial index when evaluating hyperextension injuries with proximal tibial epiphyseal fractures.

Palomba: Pharmacyclics: Honoraria; Juno: Honoraria; Celgene: Honoraria; Merck: Honoraria; Novartis: Honoraria; Regeneron: Research Funding; Juno: Research Funding; Genentech: Research Funding. Gordon:Zylem Biosciences: Patents & Royalties: Patents, No Royalties. Siddiqi:Juno: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; BeiGene: Other: DMC member; Juno Therapeutics, Pharmacyclics LLC, an AbbVie Company, AstraZeneca, Celgene, Kite Pharma, and BeiGene: Consultancy; Pharmacyclics LLC, an AbbVie Company, Seattle Genetics, Janssen, and AstraZeneca: Speakers Bureau; Pharmacyclics LLC, an AbbVie Company, Juno Therapeutics, KITE Pharma, AstraZeneca, TG Therapeutics, Celgene, Oncternal, and BeiGene: Research Funding; AstraZeneca: Other: Travel/accommodations/expenses; Astrazenca: Membership on an entity's Board of Directors or advisory committees; PCYC: Membership on an entity's Board of Directors or advisory committees. Abramson:Celgene: Honoraria, Other: Scientific Advisory Board; Juno Therapeutics: Other: Scientific Advisory Board; AbbVie: Other: Scientific Advisory Board; EMD Serono: Other: Scientific Advisory Board; Genentech/Roche: Other: Scientific Advisory Board; Janssen: Other: Scientific Advisory Board; Karyopharm: Other: Scientific Advisory Board; Gilead: Other: Scientific Advisory Board; Verastem: Other: Scientific Advisory Board; Bayer: Other: Scientific Advisory Board; Merck: Other; KIte Pharma: Other; Novartis: Other; Amgen: Other; Seattle Genetics: Other; Allogene: Other; Morphosys: Other; C4 Therapeutics: Other; BeiGene: Other; AstraZeneca: Honoraria; Incyte: Honoraria. Kamdar:Seattle Genetics: Speakers Bureau; Karyopharm: Consultancy; BMS: Consultancy; Abbvie: Consultancy; AstraZeneca: Consultancy; Pharmacyclics: Consultancy. Lunning:Acrotech: Consultancy; ADC Therapeutics: Consultancy; Bristol Meyers Squibb: Consultancy, Honoraria, Research Funding; Curis: Research Funding; Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; TG Therapeutics: Research Funding; Verastem: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Legend: Consultancy; Beigene: Consultancy, Honoraria; Aeratech: Consultancy, Honoraria. Maloney:Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; MorphoSys: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria; A2 Biotherapeutics: Consultancy, Current equity holder in publicly-traded company, Honoraria; Juno Therapeutics: Consultancy, Honoraria, Patents & Royalties: Patents are pending, but not issued, licensed, no royalties, no licensees., Research Funding; Bioline Rx: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Andreadis:Genentech: Other: Spouse Employee (salary and stock); Novartis: Research Funding; Celgene/Juno: Research Funding; Amgen: Research Funding; Merck: Research Funding; Gilead/Kite: Other: Advisor; Jazz Pharmaceuticals: Other: Advisor; Astellas: Other: Advisor; Seattle Genetics: Other: Advisor; Karyopharm: Other: Advisor; Incyte: Other. Arnason:Regeneron: Consultancy; Juno: Consultancy. Ghosh:Forty Seven Inc: Consultancy, Other: Research Bureau, Research Funding; Genmab: Consultancy, Speakers Bureau; AbbVie: Speakers Bureau; Karyopharm: Consultancy; Juno/Celgene/Bristol-Myers Squibb: Consultancy, Research Funding; Kite/Gilead: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Roche/Genentech: Research Funding; SGN: Consultancy, Research Funding, Speakers Bureau; TG Therapeutics: Consultancy, Research Funding; Celgene/Bristol-Myers Squibb: Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding, Speakers Bureau. Mehta:Innate Pharmaceuticals: Research Funding; Kite/Gilead: Research Funding; Merck: Research Funding; Gelgene/BMS: Research Funding; Oncotartis: Research Funding; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Juno Parmaceuticals/BMS: Research Funding; fortyseven Inc/Gilead: Research Funding; Takeda: Research Funding; Roche-Genentech: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Affimed: Research Funding. Farazi:Juno Therapeutics, a Bristol-Myers Squibb Company: Current Employment; Bristol-Myers Squibb: Current equity holder in publicly-traded company. Garcia:Juno Therapeutics, a Bristol-Myers Squibb Company: Current Employment; Bristol-Myers Squibb Company: Current equity holder in publicly-traded company. Dehner:Juno Therapeutics, a Bristol-Myers Squibb Company: Current Employment; Bristol-Myers Squibb: Current equity holder in publicly-traded company. Ogasawara:Bristol-Myers Squibb: Current Employment; Bristol-Myers Squibb: Current equity holder in publicly-traded company. Gao:Bristol-Myers Squibb: Current equity holder in publicly-traded company; Bristol-Myers Squibb: Current Employment. Wang:Juno: Consultancy, Research Funding; Acerta Pharma: Research Funding; Loxo Oncology: Consultancy, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; InnoCare: Consultancy; Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; MoreHealth: Consultancy; Lu Daopei Medical Group: Honoraria; Beijing Medical Award Foundation: Honoraria; OncLive: Honoraria; Molecular Templates: Research Funding; Verastem: Research Funding; Dava Oncology: Honoraria; Guidepoint Global: Consultancy; Pulse Biosciences: Consultancy; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Oncternal: Consultancy, Research Funding; Nobel Insights: Consultancy; OMI: Honoraria, Other: Travel, accommodation, expenses; Targeted Oncology: Honoraria; BioInvent: Research Funding; VelosBio: Research Funding.

Background:Chimeric antigen receptor (CAR) T cell therapy is generally limited to inpatient settings; yet, exploration of outpatient infusion and monitoring is ongoing. Information on health care resource utilization (HCRU) and costs associated with CAR T cell therapy administration is limited and may differ by postinfusion monitoring site. Liso-cel is an investigational, CD19-directed, defined composition, 4-1BB CAR T cell product administered at equal target doses of CD8+and CD4+CAR+T cells. An interim analysis from the OUTREACH study (NCT03744676) observed lower HCRU with outpatient vs inpatient administration (Bachier et al. J Clin Oncol2020;38:8037). The patient journey after CAR T cell therapy administration may differ for patients with outpatient vs inpatient monitoring and may result in varying costs of care. This study estimated the cost of postinfusion monitoring by site of care for patients with R/R LBCL who received third-line or later treatment with liso-cel in the TRANSCEND NHL 001 (TRANSCEND; NCT02631044) and OUTREACH clinical trials.

Palomba: Regeneron: Research Funding; Juno Therapeutics, a Bristol-Meyers Squibb Company: Honoraria, Research Funding; Genentech: Research Funding; Merck: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Pharmacyclics: Honoraria. Jun:Bristol-Myers Squibb Company: Current Employment, Current equity holder in publicly-traded company. Garcia:Bristol-Myers Squibb Company: Current equity holder in publicly-traded company; Juno Therapeutics, a Bristol-Myers Squibb Company: Current Employment. Lymp:Bristol-Myers Squibb Company: Current equity holder in publicly-traded company; Juno Therapeutics, a Bristol-Myers Squibb Company: Current Employment. McGarvey:Pfizer, Inc.: Ended employment in the past 24 months; BluePath Solutions: Current Employment. Gitlin:BMS: Research Funding. Pelletier:BMS: Current Employment, Current equity holder in publicly-traded company. Nguyen:BluePath Solutions: Current Employment.

Background:Mantle cell lymphoma (MCL) is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL). Most patients with MCL relapse after first-line immunochemotherapy, with poor responses to salvage therapy. Chimeric antigen receptor (CAR) T cell therapy has shown clinical efficacy in patients with relapsed/refractory (R/R) NHL. We report the results of the dose-finding and dose-expansion parts of the ongoing phase 1 TRANSCEND NHL 001 study (NCT02631044) in patients with R/R MCL (MCL cohort) who received lisocabtagene maraleucel (liso-cel), an investigational, CD19-directed, defined composition, 4-1BB CAR T cell product administered at equal target doses of CD8+and CD4+CAR+T cells.

Powers: Celgene: Employment. Parisi:Celgene: Employment. Kim:Juno Therapeutics, a Celgene Company: Employment. Garcia:Celgene: Employment, Equity Ownership. Dehner:Juno Therapeutics, a Celgene Company: Employment. Maloney:Juno Therapeutics: Honoraria, Patents & Royalties: patients pending , Research Funding; Celgene,Kite Pharma: Honoraria, Research Funding; BioLine RX, Gilead,Genentech,Novartis: Honoraria; A2 Biotherapeutics: Honoraria, Other: Stock options .

Abramson: AbbVie Inc, Amgen Inc, Bayer HealthCare Pharmaceuticals, Celgene Corporation, EMD Serono Inc, Genentech, Gilead Sciences Inc, Janssen Biotech Inc, Juno Therapeutics, a Celgene Company, Karyopharm Therapeutics, Kite Pharma Inc, Merck, Novartis, Seattle Gen: Consultancy. Palomba:Kite Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Merck & Co Inc.: Consultancy; MSK (IP for Juno and Seres): Patents & Royalties; Noble Insights: Consultancy; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Seres Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; STRAXIMM: Membership on an entity's Board of Directors or advisory committees; Evelo: Equity Ownership; Hemedicus: Speakers Bureau. Gordon:Gilead: Other: Advisory Board; Bayer: Other: Advisory Board; Juno/Celgene: Other: Advisory Board, Research Funding; Zylem LLC: Other: co-founder; research in nanoparticles in cancer. Lunning:Spectrum: Consultancy; Seattle Genetics: Consultancy; Portola: Consultancy; OncLive: Consultancy; Novartis: Consultancy; Kite: Consultancy; Gilead Sciences, Inc.: Consultancy; DAVA: Consultancy; Bayer: Consultancy; AbbVie: Consultancy; TG Therapeutics: Consultancy, Research Funding; MiRagen: Research Funding; Juno Therapeutics: Consultancy, Research Funding; Janssen Scientific Affairs, LLC: Consultancy, Research Funding; Curis: Research Funding; VANIUM: Consultancy; Verastem: Consultancy. Wang:Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics: Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; MoreHealth: Consultancy, Equity Ownership; Acerta Pharma: Consultancy, Research Funding; Kite Pharma: Consultancy, Research Funding; Guidepoint Global: Consultancy; BioInvent: Consultancy, Research Funding; VelosBio: Research Funding; Loxo Oncology: Research Funding; Celgene: Honoraria, Research Funding; Juno Therapeutics: Research Funding; Aviara: Research Funding; Dava Oncology: Honoraria. Arnason:Celgene/Juno: Consultancy; Regeneron Pharmaceuticals, Inc.: Consultancy. Mehta:Pharmacyclics: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Spectrum: Consultancy, Speakers Bureau; Imbrium therapeutics: Consultancy; Roche-Genentech: Research Funding; Incyte: Research Funding; Kite/Gilead: Research Funding, Speakers Bureau; Takeda: Research Funding; Rhizen: Research Funding; ADC therapeutics: Research Funding; Forty Seven Inc: Research Funding; Juno/Celgene: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding, Speakers Bureau; Astex: Research Funding; TG Therapeutics: Research Funding; miRagen: Research Funding; Kyowa-Kirin: Consultancy, Speakers Bureau; Astra-Zeneca: Speakers Bureau; Sanofi: Consultancy. Maloney:Celgene,Kite Pharma: Honoraria, Research Funding; Juno Therapeutics: Honoraria, Patents & Royalties: patients pending , Research Funding; BioLine RX, Gilead,Genentech,Novartis: Honoraria; A2 Biotherapeutics: Honoraria, Other: Stock options . Andreadis:Juno: Research Funding; Pharmacyclics: Research Funding; Genentech: Consultancy, Employment; Kite: Consultancy; Gilead: Consultancy; Jazz Pharmaceuticals: Consultancy; Roche: Equity Ownership; Novartis: Research Funding; Celgene: Research Funding; Merck: Research Funding. Sehgal:Merck: Research Funding; Juno/Celgene: Research Funding; Kite/Gilead: Research Funding. Ghosh:AstraZeneca: Honoraria, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; SGN: Consultancy, Honoraria, Research Funding, Speakers Bureau; TG Therapeutics: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Genentech: Research Funding; Forty Seven Inc: Research Funding. Albertson:Juno Therapeutics, a Celgene Company: Employment, Equity Ownership. Garcia:Celgene: Employment, Equity Ownership. Kostic:Juno Therapeutics, a Celgene Company: Employment. Li:Juno Therapeutics, a Celgene Company: Employment. Kim:Juno Therapeutics, a Celgene Company: Employment. Siddiqi:TG Therapeutics: Research Funding; Kite, A Gilead Company: Research Funding; Seattle Genetics: Speakers Bureau; Janssen: Speakers Bureau; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; PCYC: Consultancy, Research Funding, Speakers Bureau; Juno Therapeutics: Consultancy, Other: travel support, Research Funding; Celgene: Research Funding; BeiGene: Research Funding.

Maloney: Juno Therapeutics: Honoraria, Patents & Royalties: patients pending , Research Funding; Celgene,Kite Pharma: Honoraria, Research Funding; BioLine RX, Gilead,Genentech,Novartis: Honoraria; A2 Biotherapeutics: Honoraria, Other: Stock options . Liu:Celgene Corporation: Employment. Nientker:Celgene Corporation: Consultancy; Pharmerit Cöoperatief U.A.: Employment. Alleman:Pharmerit Cöoperatief U.A.: Employment; Celgene Corporation: Consultancy. Garcia:Celgene: Employment, Equity Ownership.

Introduction:Large B-cell lymphoma (LBCL) is the most common subtype of non-Hodgkin lymphoma. Frontline treatment is curative in ~60% of patients (pts); however, ~30% of pts relapse and ~10% are refractory to frontline treatment. Treatment options for pts with relapsed/refractory (R/R) disease, especially in the third-line or greater (3L+) setting, have been primarily salvage chemotherapies (CTs). Recently, 2 CAR T cell products, axicabtagene ciloleucel (Yescarta®) and tisagenlecleucel (Kymriah®), and the antibody-drug conjugate, polatuzumab vedotin (Polivy®), were approved in the 3L setting. A systematic literature review (SLR) of R/R LBCL was conducted to identify relevant evidence on clinical outcomes in LBCL pts, including these new therapies, within the second-line and greater (2L+) or 3L+ setting, and to define the unmet medical need.

Background:CAR T cell therapies have demonstrated high response rates in patients (pts) with R/R B cell NHL. Liso-cel is an investigational anti-CD19, defined composition, 4-1BB CAR T cell product administered at target doses of CD4+ and CD8+ CAR T cells. The seamless phase 1 TRANSCEND NHL 001 study evaluated liso-cel in pts with R/R large B cell NHL (NCT02631044). We present data with long-term follow-up from pts treated in the DLBCL cohort.

Background:Decreased health-related quality of life (HRQoL) is associated with R/R large B cell lymphoma. TRANSCEND NHL 001 is an open-label, multicenter, multicohort, seamless design phase 1 study in adult pts with R/R B cell NHL receiving liso-cel, an investigational, anti-CD19, defined composition, 4-1BB, chimeric antigen receptor (CAR) T cell product administered at a target dose of CD4+ and CD8+ CAR T cells (NCT02631044). In the diffuse large B cell lymphoma (DLBCL) cohort of TRANSCEND NHL 001, patient-reported outcomes were evaluated using the validated European Organization for Research and Treatment of Cancer quality of life questionnaire C30 (EORTC QLQ-C30), which assesses HRQoL and symptom burden, and the EuroQol 5 Dimensions 5 Levels (EQ-5D-5L; health state index score comprising the EQ-5D and EQ-visual analog scale [VAS]), which assesses health utility impact of liso-cel.

The article presents interviews with Ashley McCreadie, assistant vice president at Woodruff-Sawyer & Co., David Fishel, associate at Higginbotham, and Kyle Ranney, account executive at Lyman & Sheets Insurance Agency. They talked about the interest of Millennials to work in the U.S. insurance industry. They identified some career advantages being offered by the industry, including flexibility and steadiness.

Palomba: Celgene: Consultancy; Pharmacyclics: Consultancy. Garcia:Juno Therapeutics, a fully owned subsidiary of Celgene: Employment, Equity Ownership. Wang:Juno Therapeutics, a fully owned subsidiary of Celgene: Employment, Equity Ownership. Dehner:Juno Therapeutics, a fully owned subsidiary of Celgene: Employment, Equity Ownership. Chung:Juno Therapeutics, a fully owned subsidiary of Celgene: Employment. Maloney:Janssen Scientific Affairs: Honoraria; GlaxoSmithKline: Research Funding; Seattle Genetics: Honoraria; Juno Therapeutics: Research Funding; Roche/Genentech: Honoraria.

Siddiqi: Juno Therapeutics: Other: Steering committee. Garcia:Juno Therapeutics, a fully owned subsidiary of Celgene: Employment, Equity Ownership. Dehner:Juno Therapeutics, a fully owned subsidiary of Celgene: Employment, Equity Ownership. Nguyen:Juno Therapeutics: Consultancy. Gitlin:Juno Therapeutics: Consultancy. Chung:Juno Therapeutics: Employment. Abramson:Verastem: Consultancy; Amgen: Consultancy; Novartis: Consultancy; Bayer: Consultancy; Juno Therapeutics: Consultancy; Gilead: Consultancy; Celgene: Consultancy; Karyopharm: Consultancy; Merck: Consultancy; Humanigen: Consultancy; Seattle Genetics: Consultancy.

Background:Relapsed/refractory (R/R) DLBCL is associated with high healthcare resource utilization (HRU) and cost (Danese 2017). Patients with R/R DLBCL have poor outcome with median OS <10 months (Van den Neste 2015). As transformative therapies are being developed for these patients, resource utilization may become an issue. Liso-cel is an investigational defined composition, CD19-directed 4-1BB CAR T cell product administered at a precise dose of CD8 and CD4 CAR T cells in a multicenter, seamless design Phase 1 pivotal trial of (R/R) DLBCL (TRANSCEND NHL 001; NCT02631044). In a recent analysis with 6 months follow-up, liso-cel treatment demonstrated a best overall response rate of 75% (55% CR) with low rates of severe cytokine release syndrome (1%) and neurologic events (13%) (Abramson 2018). The objective of this analysis is to characterize HRU, including site of care, associated with liso-cel in an interim analysis of the TRANSCEND pivotal trial.

Introduction:

Introduction

Background

The article provides information on how to tackle technical and logistical issues during live music performances. It suggests to daily double check the equipment when handling technical and logistical issues, and immediately remedy the situation if catching a faulty cable. It recommends to assure that the performance space has enough room for speakers and playback system.

Introduction: Cancer patients receiving myelosuppressive chemotherapy often have suppressed white blood cell counts and are at risk for febrile neutropenia (FN). Treatment with granulocyte-colony stimulating factors (G-CSFs) after administration of chemotherapy is indicated for patients with a clinically significant risk of FN. In the US most doses of G-CSFs are administered in the clinic during separate visits after the chemotherapy session, to ensure on-label administration. Patients typically must return to the clinic between 1 and 7 times per chemotherapy cycle for G-CSF injections. Travel time and distance to specialized cancer care can be significant, and was previously reported to average 26 minutes round-trip for residents of the continental US, and considerably longer for some sub-populations and geographic areas (Onega et al. Cancer 2008). Travel distance has also been linked to reduced access to needed care. This study examined the travel burden specifically for a national sample of US cancer patients who are often indicated for G-CSF therapy.

Stephens: Amgen, Inc.: Research Funding. Bensink:Amgen, Inc.: Employment, Equity Ownership. Brotherton:Prima Health Analytics: Research Funding. Chandler:Amgen, Inc.: Employment, Equity Ownership. Garcia:Amgen, Inc.: Employment, Research Funding. Hollenbeak:Prima Health Analytics: Research Funding.

Li: Amgen, Inc.: Employment, Equity Ownership. Off Label Use: This abstract describes costs associated with same-day administration of pegfilgrastim, which is an off label use of pegfilgrastim. As noted in the abstract text, "Per indication, pegfilgrastim should not be administered between 14 days before and 24 hours after cytotoxic chemotherapy.". Zhang:Amgen Inc.: Other: Internship. Lin:Amgen Inc.: Employment, Other: stock ownership. Fust:Optum: Employment; Amgen Inc.: Consultancy, Research Funding. Garcia:Amgen Inc: Employment, Equity Ownership.

Introduction: Granulocyte colony-stimulating factors such as pegfilgrastim (Neulasta®) can reduce the incidence of febrile neutropenia, a life-threatening side effect of myelosuppressive chemotherapy. According to current FDA-approved prescribing information, pegfilgrastim should not be administeredbetween 14 days before and 24 hours after administration of myelosuppressive chemotherapy. Previous research indicates that same- vs next-day administration of pegfilgrastim may be associated with worse patient outcomes, and current guidelines from both ASCO and NCCN recommend use of pegfilgrastim 1-3 days after chemotherapy. A recent health care claims database analysis has shown that same-day pegfilgrastim was administered in ~13% of chemotherapy cycles, but little is known about physician rationale for administering same-day pegfilgrastim. Here, we describe the results of a cross-sectional, web-based physician survey describing the practice- and patient-related factors that physicians report to have affected their decision to administer same-day pegfilgrastim.

Darden: Amgen Inc: Research Funding; RTI Health Solutions: Employment. Off Label Use: This abstract assesses physician rationale for same-day administration of pegfilgrastim, which is an off-label use of pegfilgrastim. As noted in the abstract text, "According to current FDA-approved prescribing information, pegfilgrastim should not be administered between 14 days before and 24 hours after administration of myelosuppressive chemotherapy.". Price:Amgen Inc.: Research Funding; RTI Health Solutions: Employment. Kaye:Amgen Inc.: Research Funding; RTI Health Solutions: Employment. Sherif:Amgen Inc.: Research Funding; RTI Health Solutions: Employment. Marion:RTI Health Solutions: Employment; Amgen Inc.: Research Funding. Tzivelekis:Amgen Inc.: Employment, Equity Ownership. Garcia:Amgen Inc: Employment, Equity Ownership. Chandler:Amgen Inc.: Employment, Equity Ownership.

Introduction:Febrile neutropenia (FN) is a serious side effect of myelosuppressive chemotherapy that often requires immediate hospitalization. FN is associated with lengthy hospital stays, increased mortality, and high costs. Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) such as pegfilgrastim can reduce risk of FN. Per indication, pegfilgrastim should not be administered between 14 days before and 24 hours after cytotoxic chemotherapy. In most clinical trials, G-CSF has been administered the day following chemotherapy, and administration 1-3 days after chemotherapy may result in a lower risk of infection than same-day administration (Burris et al, J Oncol Pract, 2010; Cheng et al, Anticancer Drugs,2014; Weycker et al, J Clin Oncol, 2015 [abst e17697]). Thus, both NCCN and ASCO recommend pegfilgrastim be given 1-3 days after chemotherapy when possible. A recent retrospective analysis of US health care claims databases showed that same-day pegfilgrastim was used in 13% of cycles (Weycker et al, Blood, 2014). Here we compare the costs of same- vs next-day use of pegfilgrastim (Neulasta®) from a US payer perspective.

Weycker: Amgen: Research Funding. Li:Amgen: Employment, Equity Ownership. Barron:Amgen: Employment, Equity Ownership. Wu:Amgen: Research Funding. Morrow:Amgen: Employment, Equity Ownership. Xu:Amgen: Employment, Equity Ownership. Reiner:Amgen: Employment, Equity Ownership. Garcia:Amgen: Employment, Equity Ownership. Mhatre:Amgen: Employment. Lyman:Amgen: Research Funding.

Background:Clinical practice guidelines recommend primary prophylactic colony-stimulating factor (CSF) when risk of febrile neutropenia (FN) is ≥20%. Evaluating FN risk among patients who receive regimens that are not documented as high risk in guidelines can be challenging, as some patients may be at a high risk based on a combination of the regimen and their risk factors.