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Richter transformation usually presents as an aggressive diffuse large B-cell lymphoma, occurs in up to 10% of patients with chronic lymphocytic leukaemia, has no approved therapies, and is associated with a poor prognosis. Pirtobrutinib has shown promising efficacy and tolerability in patients with relapsed or refractory B-cell malignancies, including those who progress on covalent Bruton tyrosine kinase (BTK) inhibitors. This study aims to report the safety and activity of pirtobrutinib monotherapy in a subgroup of patients with Richter transformation from the multicentre, open-label, phase 1/2 BRUIN study.

Chimeric antigen receptor (CAR) T-cell therapy has altered the treatment of lymphoid malignancies, but it is associated with acute toxicities and so-called “on-target, off-tumor” effects that place patients at risk for infectious complications. Respiratory viral infections (RVIs) are a common, but poorly characterized complication of CAR T-cell therapy.

Background:Treatment options for elderly unfit/frail (U/F) patients (pts) with diffuse large B-cell lymphoma (DLBCL) are often limited due to comorbidities or functional decline. Less toxic, efficacious alternatives to full-dose chemoimmunotherapy (CIT) are needed. Mosunetuzumab (Mosun) is a first-in-class CD20xCD3 T-cell engaging bispecific antibody that redirects T cells to eliminate B cells. Mosun monotherapy has demonstrated efficacy, durable complete responses (CR), and manageable safety in U/F pts with untreated DLBCL (NCT03677154; Olszewski et al. ASH 2022). Subgroup analysis from an ongoing Phase Ib/II study (NCT03671018) of Mosun plus polatuzumab vedotin (Pola; M-Pola) in pts with relapsed/refractory DLBCL demonstrated efficacy and a manageable safety profile in pts ≥65 years (yrs) (Olszewski et al. ASH 2022). We report preliminary efficacy and safety data from the M-Pola cohort of study NCT03677154 in elderly U/F pts with newly diagnosed DLBCL.

Background:Richter transformation (RT) occurs in up to 10% of patients with chronic lymphocytic leukemia (CLL), typically presents as an aggressive diffuse large B-cell lymphoma (DLBCL) and is associated with poor survival. RT has no approved standard therapy; and clinical trial enrollment is the preferred first line of therapy. Pirtobrutinib, a highly selective, non-covalent (reversible) BTKi, that inhibits both wildtype and C481-mutant BTK with equal low nM potency, has favorable oral pharmacology that enables continuous BTK inhibition throughout the dosing interval. Pirtobrutinib demonstrated durable overall response rates (ORR) and was well tolerated in patients (pts) with poor-prognosis B-cell malignancies regardless of prior therapy. Here we provide updated safety and efficacy of pirtobrutinib in RT pts from the phase 1/2 BRUIN trial (NCT03740529).

Olszewski: Spectrum Pharmaceuticals: Research Funding; TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding; Genentech, Inc.: Research Funding. Avigdor:Takeda, Gilead, Pfizer: Consultancy, Honoraria; Janssen, BMS: Research Funding. Babu:Amgen: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Fort Wayne Medical Oncology & Hematology: Current Employment, Current equity holder in publicly-traded company; Lilly: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Sanofi: Research Funding; Janssen Oncology: Research Funding; Lutheran Hospital: Other; Bayer: Honoraria; AstraZeneca: Consultancy, Honoraria; AstraZeneca/MedImmune: Research Funding; Boehringer Ingelheim: Consultancy; Alexion Pharmaceuticals: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding, Speakers Bureau; Argenx: Consultancy, Research Funding; Novartis: Research Funding; Genentech, Inc./ F. Hoffmann-La Roche: Research Funding; Syndax: Research Funding; Nektar: Research Funding; Merck: Research Funding; AbbVie: Research Funding; TG Therapeutics: Research Funding. Levi:Abbvie Inc: Consultancy, Research Funding. Abadi:Abbvie Inc: Research Funding; Roche, Gilead, Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Holmes:Texas Oncology PA: Current Employment; Gilead/Kite, Celgene/Juno, Rigel, Karyopharm, Janssen, Dova: Consultancy; Gilead/Kite, Novartis, Autolus, Celgene/Juno/bluebird, Genentech, Inc., Rigel, Janssen, Unum, ADC Therapeutics, Seattle Genetics, Incyte, Verastem: Research Funding; Kite, Karyopharm, Seattle Genetics, Rigel, Dova: Speakers Bureau. McKinney:UNUM, Molecular Templates, Incyte, Beigene, Denovo Biopharma, Pharmacyclics, Nordic Nanovector, BMS, Genentech, Inc., Celgene: Research Funding; Kite/Gilead: Honoraria, Speakers Bureau; Kite/Gilead, Seattle Genetics, Molecular Templates, BTG, Pharmacyclics, Verastem, Genentech, Inc., Celgene: Consultancy. McCord:F. Hoffmann-La Roche: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Xie:F. Hoffmann-La Roche: Current Employment. Chen:Janssen Pharmaceuticals: Current equity holder in publicly-traded company; Bristol-Myer Squibb: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Sarouei:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Qayum:F. Hoffmann-La Roche: Current Employment. O'Hear:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. Sellam:F. Hoffmann-La Roche: Current Employment. Eradat:UCLA Medical Center, David Geffen school of Medicine at UCLA: Current Employment; Genentech, Inc.: Consultancy, Honoraria, Research Funding, Speakers Bureau; F. Hoffmann-La Roche: Consultancy, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Astrazeneca, Atara, Kite, Juno, Acerta, BeiGene, Celgene: Research Funding.Mosunetuzumab (RG7828; CD20-TDB) is a full-length, fully humanized immunoglobulin G1 (IgG1) bispecific antibody targeting both CD3 (on the surface of T cells) and CD20 (on the surface of B cells). Mosunetuzumab redirects T cells to engage and eliminate malignant B cells. Mosunetuzumab is an investigational agent.

Introduction:Up to 30% of patients (pts) aged ≥75 years do not receive standard chemoimmunotherapy (CIT) as first-line (1L) treatment for diffuse large B-cell lymphoma (DLBCL) due to concerns about frailty and comorbidities. Poor outcomes are commonly reported for elderly/unfit pts with 1L DLBCL who receive no treatment, reduced-dose R-CHOP or other therapies such as R-CVP and R-bendamustine (Morrison, et al. J Geriatr Oncol 2020); less toxic, efficacious alternatives to full-dose CIT are needed. Mosunetuzumab (Mosun) is a full-length, fully humanized IgG1 CD20/CD3 bispecific antibody that redirects T cells to engage and eliminate malignant B cells. Single-agent Mosun has shown promising efficacy (including durable complete responses [CRs]) and tolerable safety in relapsed/refractory DLBCL pts in an ongoing Phase I study (GO29781; NCT02500407; Bartlett, et al. ASCO 2019, Schuster, et al. ASH 2019). Here we present early clinical data with Mosun as 1L therapy for elderly/unfit pts with DLBCL.

The article focuses on the questions raised to Donald Trump Administration’s initial approach on the role of public participation and intergovernmental coordination in federal land management. It mentions the part of federal land policy to both Democratic and Republican presidential political party platforms in 2016. It cites that public lands exemplify democracy in two ways which include allowing all Americans in the decision making processes and allowing equal access to federal lands.

Temperature plays an important role in the growth and development of insects, and the temperature at which an insect develops can affect both behavior and reproduction in adult insects. This study was conducted to determine the effects of temperature on development and survival in the egg and larval stages of Osmia cornifronsRadozskowski (Hymenoptera: Megachilidae) over a broad range of temperatures. O. cornifronsindividuals were placed in environmental chambers at 5, 13, 21, 29, 37, and 45 °C and their development was tracked daily. Developmental data was modelled using the Briére function and simulated by incorporating the developed model and Weibull function. Models were validated with developmental data from randomly selected bees at sites in Morgantown (n = 28) and Kearneysville (n = 78), West Virginia, USA. Osmia cornifronseggs survived at 13, 21, and 29 °C, but were unable to survive at other temperatures. Larvae survived at 21 and 29 °C, with 88.5 and 45.5% survival, respectively. The thermal window for the development of egg and 1st instar was 17.99 °C, and for 2nd instar to prepupa was 12.58 °C. Nearly all validation data fell within the 95% prediction interval, indicating that the models accurately represented the thermal biology of O. cornifronsin field. The narrow thermal window found in this study for O. cornifronslarval development indicates that O. cornifronsis sensitive to temperature change during this life history stage. Implications of the thermal requirements of O. cornifronsfor propagation and management are discussed.

Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1, JAK3, STAT3, and SOCS1. We also identified mutations in KRAS, TP53, and TERT. Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. We modeled the effects of SETD2 loss in vivo by developing a T cell–specific knockout mouse. These mice manifested an expansion of γδ T cells, indicating novel roles for SETD2 in T cell development and lymphomagenesis. Our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease and may inform future classification schemes.

GNA13 is the most frequently mutated gene in germinal center (GC)-derived B-cell lymphomas, including nearly a quarter of Burkitt lymphoma and GC-derived diffuse large B-cell lymphoma. These mutations occur in a pattern consistent with loss of function. We have modeled the GNA13-deficient state exclusively in GC B cells by crossing the Gna13 conditional knockout mouse strain with the GC-specific AID-Cre transgenic strain. AID-Cre+ GNA13-deficient mice demonstrate disordered GC architecture and dark zone/light zone distribution in vivo, and demonstrate altered migration behavior, decreased levels of filamentous actin, and attenuated RhoA activity in vitro. We also found that GNA13-deficient mice have increased numbers of GC B cells that display impaired caspase-mediated cell death and increased frequency of somatic hypermutation in the immunoglobulin VH locus. Lastly, GNA13 deficiency, combined with conditional MYC transgene expression in mouse GC B cells, promotes lymphomagenesis. Thus, GNA13 loss is associated with GC B-cell persistence, in which impaired apoptosis and ongoing somatic hypermutation may lead to an increased risk of lymphoma development.

GNA13is the most frequently mutated gene in germinal center (GC)-derived B-cell lymphomas, including nearly a quarter of Burkitt lymphoma and GC-derived diffuse large B-cell lymphoma. These mutations occur in a pattern consistent with loss of function. We have modeled the GNA13-deficient state exclusively in GC B cells by crossing the Gna13conditional knockout mouse strain with the GC-specific AID-Cretransgenic strain. AID-Cre+GNA13-deficient mice demonstrate disordered GC architecture and dark zone/light zone distribution in vivo, and demonstrate altered migration behavior, decreased levels of filamentous actin, and attenuated RhoA activity in vitro. We also found that GNA13-deficient mice have increased numbers of GC B cells that display impaired caspase-mediated cell death and increased frequency of somatic hypermutation in the immunoglobulin VHlocus. Lastly, GNA13 deficiency, combined with conditional MYCtransgene expression in mouse GC B cells, promotes lymphomagenesis. Thus, GNA13 loss is associated with GC B-cell persistence, in which impaired apoptosis and ongoing somatic hypermutation may lead to an increased risk of lymphoma development.

No abstract.

Background:Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma (NHL). Although most patients with FL respond well to first-line therapy, they will inevitably relapse, and the subsequent course is often characterized by a pattern of recurrent relapses with progressively shorter intervals between treatment lines. Moreover, the use of multiple consecutive therapies often leads to refractory disease with severely limited treatment options, demonstrating the need for new therapies for this patient population. Currently approved phosphoinositide 3-kinase (PI3K) inhibitors are often poorly tolerated. Parsaclisib, a potent, highly-selective, next-generation PI3Kδ inhibitor, has shown promising activity in patients with previously treated B-cell malignancies. Here, we report preliminary results of CITADEL-203 (NCT03126019), a multicenter, open-label phase 2 study of parsaclisib in relapsed or refractory (R/R) FL.

Background: Allogeneic hematopoietic transplantation (HCT) is frequently considered for patients (pts) with relapsed T-cell lymphoma (TCL) and less often as consolidation of initial therapy. Outcomes from prior registry data show that only 31% of pts remain disease free 3 years after HCT (Smith et al. JCO 2013). However, several single institution studies have superior outcomes. We previously presented an analysis of allogeneic transplant in T-cell lymphoma but have expanded this effort to 12 academic centers with longer follow up (Mehta-Shah ASH 2017).

Mehta-Shah: Corvus: Research Funding; Genetech/Roche: Research Funding; Verastem: Research Funding; Karyopharm Therapeutics: Consultancy; Bristol Myers-Squibb: Research Funding; Celgene: Research Funding; C4 Therapeutics: Consultancy; Kyowa Hakko Kirin: Consultancy; Innate Pharmaceuticals: Research Funding. Dahi:Kite: Consultancy. Sauter:Sanofi-Genzyme: Consultancy, Research Funding; Kite - a Gilead Company: Consultancy; Spectrum Pharamaceuticals: Consultancy; Gamida Cell: Consultancy; GSK: Consultancy; Bristol-Myers Squibb: Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Genmab: Consultancy; Precision Biosciences: Consultancy, Research Funding; Juno Therapeutics: Consultancy, Research Funding. Moskowitz:Merck: Research Funding; Imbrium Therapeutics, L.P.: Consultancy; Bristol-Myers Squibb: Research Funding; Miragen Therapeutics: Consultancy; Merck: Consultancy; Seattle Genetics: Consultancy; Incyte: Research Funding; Seattle Genetics: Research Funding. Jacobsen:Novartis: Research Funding; Takeda: Honoraria; Pharmacyclics: Research Funding; F. Hoffmann-LaRoche: Research Funding; Astra-Zeneca: Consultancy; Acerta: Consultancy; Merck: Consultancy. William:Celgene: Consultancy, Honoraria; Guidepoint Global: Consultancy; Seattle Genetics: Research Funding; Dova: Research Funding; Incyte: Research Funding; Merck: Research Funding; Kyowa Kirin: Consultancy, Honoraria. Barta:Monsanto: Consultancy; Pfizer: Honoraria; Janssen: Honoraria; Seattle Genetics: Honoraria, Research Funding; Atara: Honoraria. Allen:Clinical Care Options: Speakers Bureau; Curio Sciences: Honoraria; Research to Practice: Speakers Bureau; Imbrium: Consultancy, Other; Bayer: Consultancy, Other. Song:Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Celgene,Takeda: Consultancy, Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Research Funding; Otsuka: Honoraria. Ruan:Celgene: Consultancy, Research Funding; Seattle Genetics: Research Funding; Kite Pharma: Consultancy; Juno: Consultancy; BMS: Consultancy, Research Funding; Pharmacyclics: Research Funding; AstraZeneca: Consultancy, Research Funding. McKinney:Kite/Gilead: Honoraria, Speakers Bureau; Kite/Gilead, Seattle Genetics, Molecular Templates, BTG, Pharmacyclics, Verastem, Genentech, Inc., Celgene: Consultancy; UNUM, Molecular Templates, Incyte, Beigene, Denovo Biopharma, Pharmacyclics, Nordic Nanovector, BMS, Genentech, Inc., Celgene: Research Funding. Beaven:Tessa Therapeutics: Research Funding; Roche: Research Funding; Seattle Genetics: Research Funding; MorphoSysAb: Research Funding; LoxoOncology: Research Funding; Celgene: Research Funding. Haverkos:Viracta THerapeutics: Consultancy. Alpdogan:Seattle Genetics: Consultancy; Kiowa Kirin: Consultancy. Porcu:Kiowa Kirin: Research Funding; Kura Oncology: Research Funding; Innate Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Galderma: Research Funding; Daiichi: Consultancy, Honoraria; Celgene: Research Funding; Cell Medica: Research Funding; Miragen: Research Funding; Verastem: Consultancy; Viracta Therapeutics: Membership on an entity's Board of Directors or advisory committees. Horwitz:Daiichi Sankyo: Research Funding; GlaxoSmithKline: Consultancy; Janssen: Consultancy; Kura Oncology: Consultancy; Myeloid Therapeutics: Consultancy; Miragen: Consultancy; ADCT Therapeutics: Consultancy, Research Funding; Aileron: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Forty Seven: Consultancy, Research Funding; Infinity/Verastem: Research Funding; Kyowa Hakka Kirin: Consultancy, Research Funding; Millenium/Takeda: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Trillium: Consultancy, Research Funding; Corvus: Consultancy; Innate Pharma: Consultancy; Mundipharma: Consultancy; Portola: Consultancy, Research Funding; Beigene: Consultancy; C4 Therapeutics: Consultancy; Verastem: Consultancy, Research Funding; Vividion Therapeutics: Consultancy; Affirmed: Consultancy; ASTEX: Consultancy.

Background:Follicular lymphoma (FL) is the second most common form of non-Hodgkin lymphoma (NHL) in Western countries, accounting for 20-30% of all NHLs (Hübel K. Hemasphere.2020;4:e317). While most patients (pts) respond well to first-line therapy, they typically experience frequent relapses and progressively shorter duration of response with subsequent lines of therapy (Batlevi CL. Blood Cancer J.2020;10:74; Rivas-Delgado A. Br J Haematol.2019;184:753-9), and increasingly refractory disease with limited treatment options. Thus, there is an unmet need for effective treatment options for pts with relapsed or refractory (R/R) FL. Parsaclisib is a potent, highly selective, next-generation phosphatidylinositol 3-kinase (PI3K)δ inhibitor. Here we report results of the primary analysis of CITADEL-203 (NCT03126019, EudraCT 2017-001624-22), a phase 2, multicenter, open-label study of parsaclisib monotherapy in R/R FL.

Introduction: Primary mediastinal large B-cell lymphoma (PMBL) is a rare non-Hodgkin lymphoma subtype that occurs predominantly in young adults, with an overall favorable prognosis. The cell of origin is presumed to be thymic medullary B-cells and the gene expression profile of PMBL is similar to classic Hodgkin lymphoma. Recent studies have begun unravelling the genomic alterations underlying PMBL. Frequent, recurrent mutations (e.g. B2M, TNFAIP3, SOCS1, STAT6, GNA13) have been reported, but most of the studies have analyzed a small number of cases. To gain further insights into disease biology, we recruited 63 cases of PMBL as part of the Atlas of Blood Cancer Genomes (ABC-G) initiative, a consortium consisting of 25 institutions.

Introduction

McKinney: Novartis: Research Funding; Nordic Nanovector: Research Funding; Molecular Templates: Consultancy, Research Funding; Kite/Gilead: Honoraria, Speakers Bureau; Incyte: Research Funding; Genetech: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy; Celgene: Consultancy, Research Funding; BTG: Consultancy; Beigene: Research Funding; ADC Therapeutics: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy; Verastem: Consultancy. Behdad: Lilly: Speakers Bureau; Roche/Foundation Medicine: Speakers Bureau; Thermo Fisher: Speakers Bureau.

Hsi: AbbVie: Research Funding; Eli Lilly: Research Funding; Cytomx: Honoraria; Seattle Genetics: Honoraria. McKinney: BTG: Consultancy; Celgene: Consultancy, Research Funding; Epizyme: Consultancy; Genetech: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Kite/Gilead: Honoraria, Speakers Bureau; Molecular Templates: Consultancy, Research Funding; Nordic Nanovector: Research Funding; Novartis: Research Funding; Pharmacyclics: Consultancy; Verastem: Consultancy; Beigene: Research Funding; ADC Therapeutics: Consultancy, Speakers Bureau. Jaye: Stemline Therapeutics: Honoraria. Cohen: Genentech, Takeda, BMS/Celgene, BioInvent, LAM, Astra Zeneca, Novartis, Loxo/Lilly: Research Funding; Janssen, Adaptive, Aptitude Health, BeiGene, Cellectar, Adicet, Loxo/Lilly, AStra ZenecaKite/Gilead: Consultancy. Behdad: Lilly: Speakers Bureau; Roche/Foundation Medicine: Speakers Bureau; Thermo Fisher: Speakers Bureau. Dave: Data Driven Bioscience: Current equity holder in publicly-traded company.

Lynch: Morphosys: Consultancy; Takeda: Research Funding; Incyte: Research Funding; TG Therapeutics: Research Funding; Rhizen: Research Funding; Bayer: Research Funding; Juno: Research Funding; Cyteir: Research Funding; Genentech: Research Funding. Avigdor: Pfizer: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; BMS: Research Funding; Janssen: Research Funding; Takeda: Consultancy, Honoraria. McKinney: ADC Therapeutics: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy; Novartis: Research Funding; Nordic Nanovector: Research Funding; Molecular Templates: Consultancy, Research Funding; Kite/Gilead: Honoraria, Speakers Bureau; Incyte: Research Funding; Genetech: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Epizyme: Consultancy; BTG: Consultancy; Beigene: Research Funding; Verastem: Consultancy. Paneesha: AbbVie: Honoraria; Bristol Myers Squibb: Honoraria; Gilead: Honoraria; Janssen: Honoraria; Roche: Honoraria; Celgene: Honoraria. Wahlin: Gilead Sciences: Research Funding; Roche: Consultancy, Research Funding. Cunningham: Celgene: Research Funding; OVIBIO: Membership on an entity's Board of Directors or advisory committees; Bayer: Research Funding; 4SC: Research Funding; Eli Lilly: Research Funding; Clovis Oncology: Research Funding; MedImmune: Research Funding; AstraZeneca: Research Funding; Roche: Research Funding. Morley: AbbVie; Takeda: Other: Conference support; Janssen: Honoraria; Kite: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Conference support. Canales: Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Sandoz: Honoraria, Speakers Bureau; Sanofi: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy; Gilead/Kite: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Eusa Pharma: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; iQone: Honoraria. Bastos-Oreiro: Takeda: Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Kite: Speakers Bureau; Gilead: Honoraria; BMS-Celgene: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; F. Hoffmann-La Roche: Honoraria, Research Funding, Speakers Bureau. Belada: Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding; Celgene: Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses, Research Funding. Zheng: Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. DeMarini: Incyte: Current Employment, Current equity holder in publicly-traded company. Jiang: Incyte: Current Employment, Current equity holder in publicly-traded company. Trněný: Gilead Sciences: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Amgen: Consultancy, Honoraria; 1st Faculty of Medicine, Charles University, General Hospital in Prague: Current Employment; Celgene: Consultancy; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Portola: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.Investigational PI3K delta inhibitor (parsaclisib) for patients with FL

Hill: Celgene (BMS): Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Gentenech: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel Support, Research Funding; Beigene: Consultancy, Honoraria, Research Funding; AstraZenica: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria; Incyte/Morphysis: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. McKinney: Novartis: Research Funding; Nordic Nanovector: Research Funding; Molecular Templates: Consultancy, Research Funding; Kite/Gilead: Honoraria, Speakers Bureau; Incyte: Research Funding; Genetech: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy; Celgene: Consultancy, Research Funding; BTG: Consultancy; Beigene: Research Funding; ADC Therapeutics: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy; Verastem: Consultancy. Neff: Spring Discovery: Consultancy, Ended employment in the past 24 months; EUSA Pharma: Speakers Bureau; Enzyvant: Consultancy. Reshef: BMS, Regeneron, TScan, Synthekine, Atara, Jasper, Bayer: Consultancy; ilead, BMS, Precision, Immatics, Atara, Takeda, Shire, Pharmacyclics, Incyte: Research Funding; Bayer: Consultancy; Gilead and Novartis: Honoraria. Oluwole: Janssen: Consultancy; Pfizer: Consultancy; Curio Science: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. Ghosh: Incyte: Consultancy, Honoraria; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Speakers Bureau; TG Therapeutics: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genmab: Consultancy, Honoraria; Epizyme: Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; ADC Therapeutics: Consultancy, Honoraria; Adaptive Biotech: Consultancy, Honoraria; AbbVie: Honoraria, Speakers Bureau; Karyopharma: Consultancy, Honoraria; Genentech: Research Funding. Chen: Actinium Pharmaceuticals: Other: Principal Investigator, SIERRA Trial, Actinium. Hernandez-Ilizaliturri: AbbVie: Other: Advisory Boards; Incyte: Other: Advisory Boards; Celgene: Other: Advisory Boards; BMS: Other: Advisory Boards; Pharmacyclics: Other: Advisory Boards; Amgen: Other: Advisory Boards; Kite: Other: Advisory Boards; Gilead: Other: Advisory Boards; Epyzime: Other: Advisory Boards. Shah: Lily: Consultancy, Honoraria, Research Funding; Miltenyi Biotec: Consultancy, Honoraria, Research Funding; Kite: Consultancy; Epizyme: Consultancy; Legend: Consultancy; Incyte: Consultancy; Umoja: Consultancy. Stephens: Epizyme: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Innate Pharma: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Adaptive: Membership on an entity's Board of Directors or advisory committees; JUNO: Research Funding; Novartis: Research Funding; Abbvie: Consultancy; AstraZeneca: Consultancy; CSL Behring: Consultancy; Celgene: Consultancy; Mingsight: Research Funding; Arqule: Research Funding. Patel: Janssen: Consultancy; Kite Pharma: Consultancy, Speakers Bureau; TG Therapeutics: Consultancy, Speakers Bureau; MEI Pharma: Consultancy; Abbvie: Consultancy; Genentech: Consultancy; Bristol Myers Squibb: Consultancy, Speakers Bureau; BeiGene: Consultancy; Morphosys: Consultancy; Pharmacyclics: Consultancy; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; ADC Therapeutics: Consultancy; Lilly: Consultancy. Pagel: Gilead: Consultancy; Actinium Pharmaceuticals: Consultancy; Kite, a Gilead Company: Consultancy; Incyte/MorphoSys: Consultancy; AstraZeneca: Consultancy; Pharmacyclics/AbbVie: Consultancy; Epizyme: Consultancy; BeiGene: Consultancy; MEI Pharma: Consultancy. Hsi: AbbVie Inc, Eli Lilly: Research Funding. Goy: Genentech/Hoffman la Roche: Research Funding; AbbVie/Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta: Consultancy, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Medscape: Consultancy; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Physicians' Education Resource: Consultancy, Other: Meeting/travel support; Xcenda: Consultancy, Honoraria; Genomic Testing Cooperative: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Leadership role; LLC(Targeted Oncology): Consultancy; Hoffman la Roche: Consultancy; Vincerx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Rosewell Park: Consultancy; Infinity/Verastem: Research Funding; MorphoSys: Honoraria, Other; Elsevier PracticeUpdate: Oncology: Consultancy, Honoraria; Xcenda: Consultancy; Bristol Meyers Squibb: Membership on an entity's Board of Directors or advisory committees; Vincerx pharma: Membership on an entity's Board of Directors or advisory committees; OncLive Peer Exchange: Honoraria; COTA (Cancer Outcome Tracking Analysis): Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Leadership role; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Elsevier's Practice Update Oncology, Intellisphere, LLC(Targeted Oncology): Consultancy; Incyte: Honoraria; AbbVie/Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Michael J Hennessey Associates INC: Consultancy; Novartis: Consultancy, Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Karyopharm: Research Funding; Bristol Meyers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Phamacyclics: Research Funding; Constellation: Research Funding; Hackensack Meridian Health, Regional Cancer Care Associates/OMI: Current Employment. Ohgami: Stemline Therapeutics: Research Funding. Andreadis: CRISPR Therapeutics: Research Funding; GenMAB: Research Funding; Novartis: Research Funding; Roche: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Epizyme: Honoraria; Incyte: Honoraria; TG Therapeutics: Honoraria; Kite: Honoraria; Karyopharm: Honoraria; Atara: Consultancy, Honoraria; BMS: Research Funding; Merck: Research Funding. Thacker: Data Driven Bioscience: Current Employment. Rozzi: Data Driven Bioscience: Current Employment. Parker: Data Driven Bioscience: Current Employment. Happ: Data Driven Bioscience: Current Employment. Dave: Data Driven Bioscience: Current equity holder in publicly-traded company.

In a survey of SAF-accredited natural resources schools, 36 of 40 educators said natural resource professionals need more training in public involvement and dispute resolution, and 96 percent of respondents said such training was important" or "essential." Despite budgetary and staff constraints, the number of SAF-accredited schools offering specific courses in these topics has grown dramatically, from a reported three in 1992 to 15 in 1997. At most schools, these topics also have been incorporated into already-required courses on policy, planning, and management. The authors describe a model course in public involvement and conflict resolution and list resources for educators.

Public involvement in water resources planning is traditionally limited. While decision makers may solicit public input, affected parties rarely have the opportunity to participate directly in the decision-making process. In recent years, this lack of meaningful public participation has been exacerbated by an increase in the number of individuals and groups interested in water management. In light of these limitations in and new demands on water resource planning, there has been a loud call for the development of new mechanisms to enhance public involvement and conflict management. The state of Montana has responded to this call by developing a state water plan through a collaborative, consensus-building process that directly involves the public in water policy decisions. In general, the process is based on the principles of environmental dispute resolution. After reviewing these principles, the design and implementation of Montana's state water plan is examined. The advantages and limitations of this collaborative, consensus-building process are outlined, along with the conditions necessary for successful implementation.

The article focuses on the new tools used by the Endangered Species Act (ESA) for the conservation of endangered and threatened species. It states that some tools such as recovery credits and conservation banks create economic incentives for landowners to get involve with the stewardship of endangered and threatened species. It mentions that the conservation planning, investments, and cross-agency coordination are supported by federal, state, and nonprofit programs.

Burnett: Molecular Templates, Inc.: Employment. Strack:Molecular Templates, Inc.: Employment. Lehner:Molecular Templates, Inc.: Employment. Higgins:Molecular Templates, Inc.: Employment, Equity Ownership. Katz:Dova: Consultancy; Stemline: Speakers Bureau.

Erba: Amgen, Celgene, Daiichi Sankyo, ImmunoGen, Incyte, Jazz Pharmaceuticals, Millennium, Novartis, Ono, Pfizer, Seattle Genetics, Sunesis: Consultancy; Celgene, Incyte, Novartis: Speakers Bureau; Agios, Amgen, Astellas Pharma, Daiichi Sankyo, ImmunoGen, Janssen, Jazz Pharmaceuticals, Juno, Millennium, Seattle Genetics: Research Funding.

Koff: Burroughs Wellcome Fund: Research Funding; V Foundation: Research Funding; Lymphoma Research Foundation: Research Funding; American Association for Cancer Research: Research Funding. Leppä:Roche: Honoraria, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees. Gang:ROCHE: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Hsi:Abbvie: Research Funding; Eli Lilly: Research Funding; Cleveland Clinic&Abbvie Biotherapeutics Inc: Patents & Royalties: US8,603,477 B2; Jazz: Consultancy. Flowers:AbbVie: Consultancy, Research Funding; Denovo Biopharma: Consultancy; BeiGene: Consultancy, Research Funding; Burroughs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; V Foundation: Research Funding; Optimum Rx: Consultancy; Millenium/Takeda: Research Funding; TG Therapeutics: Research Funding; Gilead: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Karyopharm: Consultancy; AstraZeneca: Consultancy; Pharmacyclics/Janssen: Consultancy, Research Funding; Spectrum: Consultancy; Bayer: Consultancy; Acerta: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding. Neff:Enzyvant: Consultancy; EUSA Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fedoriw:Alexion Pharmaceuticals: Other: Consultant and Speaker. Reddy:Genentech: Research Funding; BMS: Consultancy, Research Funding; Celgene: Consultancy; KITE Pharma: Consultancy; Abbvie: Consultancy. Mason:Sysmex: Honoraria. Behdad:Loxo-Bayer: Membership on an entity's Board of Directors or advisory committees; Thermo Fisher: Membership on an entity's Board of Directors or advisory committees; Pfizer: Other: Speaker. Burton:Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dave:Data Driven Bioscience: Equity Ownership.

Munoz: Pharmacyclics /Janssen: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy; Fosunkite: Speakers Bureau; AstraZeneca: Speakers Bureau; Kyowa: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene/Juno: Consultancy, Research Funding; Genentech: Consultancy, Research Funding, Speakers Bureau; Kite/Gilead: Consultancy, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy; Alexion: Consultancy; Portola: Research Funding; Incyte: Research Funding; Bayer: Consultancy, Speakers Bureau; Merck: Consultancy. Jaglowski:Kite: Consultancy, Other: advisory board, Research Funding; Novartis: Consultancy, Other: advisory board, Research Funding; Unum Therapeutics Inc.: Research Funding; Juno: Consultancy, Other: advisory board. Isufi:Celgene: Consultancy; Novartis: Consultancy; Astra Zeneca: Consultancy. Stiff:Gamida-Cell: Research Funding; Incyte: Research Funding; Cellectar: Research Funding; Unum: Research Funding; Gilead/Kite Pharma: Consultancy, Honoraria, Research Funding; Amgen: Research Funding. Sachs:Unum Therapeutics Inc.: Employment. Ranger:Unum Therapeutics Inc.: Employment. Harris:Unum Therapeutics Inc.: Employment. Payumo:Unum Therapeutics Inc.: Employment. Akard:Bristol-Myers Squibb: Speakers Bureau; Gilead: Speakers Bureau; Takeda: Speakers Bureau; Novartis: Speakers Bureau; Celgene: Speakers Bureau.

Background:The Antibody-Coupled T-cell Receptor (ACTR) platform is an autologous engineered T-cell therapy that combines the cell-killing ability of T cells and the tumor-targeting ability of co-administered antibodies to exert potent antitumor immune responses. ACTR087 comprises the extracellular domain of CD16 linked to a CD3ζ-signaling domain and a 4-1BB co-stimulatory domain.

Introduction:

Background

Follicular Lymphoma (FL) is the most common indolent lymphoma derived from light zone germinal center B cells and characterized by a t(14;18) translocation resulting in upregulation of BCL2in over 80% of cases. This translocation alone is not sufficient for tumorogenesis, and must be combined with additional genetic mutations to transform B cells. FL is incurable and the disease course can be highly varied, with survival ranging from a few months to decades following diagnosis and treatment with standard chemoimmunotherapy. The heterogeneity of FL poses major challenges to identifying the association of genetic alterations and clinical outcome.

This article focuses on the Klamath Project, which aims at resolving the water problems in the Klamath Basin in Oregon. As with most lakes in the Klamath basin, Upper Klamath Lake has shrunk about 30 per cent since the late 1800s due to diking and draining to create more arable land. Wetlands in the basin are now 20 per cent of their historical size. Through a network of headgates, canals, and ditches, the U.S. Bureau of Reclamation manages the Klamath Project in the upper basin, providing irrigation water to about 1,400 farms. Annual on-farm crop revenues exceed $100 million. Competition is perhaps fiercest for the basin's water supply--a limited resource stretched to meet a diversifying and growing demand. Even with the dams and natural lakes and wetlands, the basin has little capacity to store surplus water in wet years for later use. The water that comes in is used, evaporates, or flows out. There is little margin for thought, and great potential for conflict among those who claim a stake in Klamath waters. While basin irrigators now work to protect their water right claims in the Oregon adjudication process, a few have considered selling out.

No relevant conflicts of interest to declare.

Introduction: