Restoring Prosperity: The State Role in Revitalizing America's Older Industrial Cities

Presents a five-part agenda and organizing plan to reinvigorate the nation's older industrial cities, and aims to mobilize governors, legislative leaders, and local constituencies toward advancing urban reform

Making local economies prosperous and resilient: The case for a modern Economic Development Administration

Congress has recently shown serious interest in reauthorizing the Economic Development Administration (EDA), a Department of Commerce agency last authorized in 2004. Congressional appropriators will also have their turn in adequately resourcing the agency, following the extraordinary demands of the pandemic and other impacts to local economies over the past two years. The urgency and importance of congressional attention cannot be overstated. America's global economic standing is under threat as digital disruption, the race for talent, and widening inequality both within and across regions challenge the nation's competitiveness. Meanwhile, the U.S. economy regularly confronts recessions, extreme weather events, supply chain breakdowns, and other shocks that disproportionately impact some local economies and further test the nation's collective ability to adapt and maintain economic resilience over the long run. In response, the country needs to marshal the economic assets that cluster in specialized ways across the regions that make up the U.S. economy--be they leading industries, research universities, entrepreneurs, or workers. These assets are critical if the nation hopes to, for instance, reduce its reliance on imports and boost supply chain resilience with greater homegrown capabilities in computer chip, renewable energy, and medical equipment design and production. Furthermore, regions with strong innovation, economic diversification, and civic capacities are more able to adapt and bounce back from economic disruptions. For these reasons, the federal government has a vested interest in spurring place-based regional economic development. To do that, it has the EDA--the one federal agency whose sole charge is to promote economic revitalization in communities of any scale, rural or urban, across the country. In short, the EDA's role is essential if the U.S. is to compete globally and prosper locally. The concern is that the EDA is not properly resourced or equipped to meet its vital mission and nationwide mandate. The agency is tasked to do too much with too little—its chronically small annual budget, combined with unpredictable special appropriations, positions the agency as marginal when, in fact, the opposite is true. The EDA is the nation's indispensable agency for supporting economic growth and resilience for communities large and small, as their leaders respond regularly to new opportunities and threats. But the policy and budget process does not yet treat it accordingly.  Congress can do its part. It can use reauthorization, now decades overdue, to elevate and modernize the EDA. It can give the agency the tools and resources to match its mandate, so it can successfully help communities and the nation adapt and rise to the immense challenges of the 21st century economy, including the range of economic disruptions today and those to come. EDA reauthorization deserves bipartisan attention and action. To inform this process, this brief provides a rationale and framework for EDA reauthorization. It is organized in three sections. First, it expands on the case for a federal role in regional economic development. It then shows why only the legislative process can better equip the EDA to improve America's capacity to innovate, compete, and expand economic opportunity for more people in more places. The brief closes with how: We recommend that the EDA become a $4 billion agency with a sharper purpose and set of roles and capabilities that match that mission. We believe this framework for EDA reauthorization and future appropriations would set the agency and its community partners up for success in today's--and tomorrow's--economy.  The authors of this brief have worked for decades with local, state, tribal, and national leaders on economic development planning, strategies, and execution. We are attuned to the demands placed on economic development actors across urban and rural communities, small and large regions, tribal nations, and downtowns and Main Streets. We are familiar with the complexity of implementation in areas such as innovation, talent development, finance, community economic development, placemaking, infrastructure, and regional and environmental planning. We came together to test a simple proposition: That despite our diverse backgrounds and experiences in economic development, we could agree on the importance of making the EDA a high-performing federal partner in spurring innovation and economic renewal for every region of the country and a policy framework for how to make that happen.

Prophylactic Ruxolitinib for Cytokine Release Syndrome in Relapse/Refractory AML Patients Treated with Flotetuzumab.

2817 Prophylactic Ruxolitinib for Cytokine Release Syndrome (CRS) in Relapse/Refractory (R/R) AML Patients Treated with Flotetuzumab Program: Oral and Poster AbstractsSession: 613. Acute Myeloid Leukemia: Clinical Studies: Poster IIIHematology Disease Topics & Pathways:AML, antibodies, Biological, CRS, Adult, Diseases, Therapies, Adverse Events, Biological Processes, Study Population, Myeloid Malignancies, Clinically relevant, TKI Monday, December 7, 2020, 7:00 AM-3:30 PM Geoffrey L Uy, MD1, Michael P. Rettig, PhD2, Stephanie Christ, MS3*, Ibrahim Aldoss, MD4, Michael T. Byrne, DO5, Harry P. Erba, MD, PhD6, Martha L. Arellano, MD7, Matthew C Foster, MD8, John E. Godwin, MD9, Farhad Ravandi, MBBS10, Peter H. Sayre, MD, PhD11, Anjali S Advani, MD12, Matthew J. Wieduwilt, MD, PhD13, Ashkan Emadi, M.D., Ph.D.14, Laura C. Michaelis, MD15, Patrick J. Stiff, MD16, Martin Wermke17*, Norbert Vey, MD18, Patrice Chevalier, MD, PhD19*, Emmanuel Gyan, MD, PhD20, Christian Recher, MD, PhD21, Fabio Ciceri, MD22*, Matteo Giovanni Carrabba, MD23*, Antonio Curti, MD PhD24, Geert Huls, MD, PhD25, Max S. Topp, MD26, Mojca Jongen-Lavrencic, MD, PhD27, John Muth, MS28*, Teia Curtis29*, Mary Beth Collins30*, Erin Timmeny31*, Kuo Guo, MSc32*, Jian Zhao, PhD32*, Kathy Tran28*, Patrick Kaminker, PhD33*, Priyanka Patel, PharmD30*, Ouiam Bakkacha, MD34*, Kenneth Jacobs, MD35*, Maya Kostova, PhD32*, Jennifer Seiler, PhD, RAC30*, Bob Lowenberg, MD, PhD36, Sergio Rutella, MD, PhD, FRCPath37, Roland B. Walter, MD, PhD, MS38, Ezio Bonvini, MD33, Jan K Davidson-Moncada, MD, PhD39 and John F. DiPersio, MD1 1Washington University School of Medicine, Saint Louis, MO2Department of Internal Medicine, Division of Oncology, Washington Univ. School of Med., Saint Louis, MO3Department of Medicine, Division of Oncology, Washington University School of Medicine, Saint Louis, MO4Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA5Department of Medicine, Division of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, TN6University of Alabama at Birmingham, Birmingham, AL7Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA8Lineberger Comprehensive Cancer Center, UNC, Chapel Hill, Chapel Hill, NC9Providence Portland Medical Center, Portland, OR10Department of Leukemia, University of Texas- MD Anderson Cancer Center, Houston, TX11University of California, San Francisco, San Francisco, CA12Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH13Moores Cancer Center, University of California, San Diego, La Jolla, CA14University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD15Division of Hematology/Oncology, Department of Medicine, The Medical College of Wisconsin Inc., Milwaukee, WI16Loyola University Chicago Stritch School of Medicine, Maywood, IL17NCT/UCC Early Clinical Trial Unit, University Hospital Carl Gustav Carus, Dresden, Germany18Hematologie clinique, Institut Paoli Clamettes, Marseille, France19Department of Hematology and Cell Therapy, CHU Nantes, Nantes, France20CHU de Tours - Hôpital Bretonneau, Tours, France21Service d\u27Hématologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France22Haematology and BMT Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy23Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy24Hematology/Oncology L. e A. Seràgnoli , Sant’Orsola-Malpighi University Hospital, Bologna, Bologna, Italy25Department of Hematology, University Medical Center Groningen, Groningen, GZ, Netherlands26Medizinische Klinik Und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany27Erasmus University Medical Center, Rotterdam, Netherlands28MacroGenics, Inc., Rockville, MD29MacroGenics, Inc., Frederick, MD30MacroGenics, Rockville31MacroGenics, Inc., ROCKVILLE, MD32MacroGenics, Rockville, MD33Macrogenics, Rockville, MD34Macrogenics,Inc, ROCKVILLE, MD35MacroGenics, Inc, Rockville, MD36Department of Hematology, Erasmus University Medical Center, Rotterdam, Netherlands37John van Geest Cancer Centre School of Science and Technology, Nottingham Trent University, Nottingham, ENG, United Kingdom38Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA39MacroGenics, Inc., Washington, DC Introduction: CRS is a potentially life-threatening toxicity observed following T cell-redirecting therapies. CRS is associated with elevated cytokines, including IL6, IFNγ, TNFα, IL2 and GM-CSF. Glucocorticosteroids (GC) and the IL6 receptor blocking antibody tocilizumab (TCZ) can reduce CRS severity; however, CRS may still occur and limit the therapeutic window of novel immunotherapeutic agents. Disruption of cytokine signaling via Janus kinase (JAK) pathway interference may represent a complementary approach to blocking CRS. Ruxolitinib (RUX), an oral JAK1/2 inhibitor approved for the treatment of myelofibrosis and polycythemia vera, interferes with signaling of several cytokines, including IFNγ and IL6, via blockade of the JAK/STAT pathway. We hypothesized that RUX may reduce the frequency and severity of CRS in R/R AML patients (pts) undergoing treatment with flotetuzumab (FLZ), an investigational CD123 x CD3 bispecific DART® molecule. Methods: Relapse/refractory (including primary induction failure, early relapse and late relapse) AML pts were included in this study. RUX pts were treated at a single site, Washington University, St. Louis, MO. RUX was dosed at 10 mg or 20mg BID days -1 through 14. Comparator (non-RUX) pts (n=23) were treated at other clinical sites. FLZ was administered at 500 ng/kg/day continuously in 28-day cycles following multi-step lead-in dosing in week 1 of cycle 1. CRS was graded per Lee criteria1. Results: As of July 1st, 2020, 10 R/R AML pts, median age 65 (range 40-82) years, have been enrolled and treated in the RUX cohort (6 at 10mg, 4 at 20 mg of RUX). All pts had non-favorable risk by ELN 2017 criteria (8 adverse and 2 intermediate); 1 (10.0%) pt had secondary AML; pt characteristics in the RUX and non-RUX cohorts were balanced, except for median baseline BM blasts which was higher in non-RUX pts: 15% (range 5-72) vs (40% (range 7-84), RUX and non-RUX pts respectively. Cytokine analysis showed statistically significant (p\u3c0.05) lower levels of IL4, IL12p70, IL13, IL15, IL17A, IFNα2, but higher levels of GM-CSF were measured in RUX vs non-RUX pts, specifically during co-administration with FLZ (Fig. 1). However, incidence and severity of CRS events were similar. In the RUX cohort, 9 (90%) pts experienced mild to moderate (grade ≤ 2; 48.6% of events were grade 1) CRS events whereas no grade ≥ 3 CRS were reported; in the non-RUX cohort, 23 (100%) pts experienced mild to moderate (grade ≤ 2; 73.1% of events were grade 1) CRS events, 1 (4.3%) grade ≥ 3 CRS was reported. Most CRS events occurred in the first 2 weeks of FLZ administration (75% and 92%, respectively). No differences in duration of CRS events were noted. However, more CRS-directed treatment was used in the RUX cohort. Five (50%) pts received a total of 12 doses of TCZ, 1 (10%) pt received GC and 1 (10%) pts received vasopressors in the RUX cohort. In the non-RUX cohort, 5 (21.7%) pts received 8 doses of TCZ, 3 (13.0%) pts received GC and 1 (3.7%) pt received vasopressors. Dose intensity (DI) at FLZ dose of 500 ng/kg/day was comparable, with median DI of 97.6% and 98.0% in RUX and non-RUX cohorts, respectively. Time to first response (TTFR; BM \u3c 5% blasts) and time on treatment (ToT) were similar between both groups. Median TTFR was 1 cycle for both groups (range 1-2 cycles), and median ToT was 1.4 (range 0.9-5.1) and 1.8 (range 1.3-5.1) months, for RUX and non-RUX pts, respectively. Complete response rate (BM \u3c 5% blasts) was similar: 4 (40%) in RUX pts, and 8 (34.8%) in non-RUX pts; 2 RUX (50%) and 5 non-RUX (62.5%) responders transitioned to stem cell transplant. Conclusion: Prophylactic RUX produced a clear difference in cytokine profiles but no discernable improvement in clinical CRS or response rates in FLZ treated patients. A larger study may be required to determine the prophylactic role of RUX in CRS