tbuckley/cabot-search huggingface dataset:
Real Time Pathological and Molecular Characterization of Aggressive B-Cell Lymphomas Based on a National Network. a Lysa Project
Authors: Christiane Copie Bergman, Elodie Bohers, Peggy Dartigues-Cuillères, Pierre-Julien Viailly, Philippe Ruminy, Vinciane Marchand, Marie-Helene Delfau-Larue, Corinne Haioun, Cyrielle Robe, Elsa Poullot, Steven Le Gouill, Yannick Le Bris, Céline Bossard, Anne Moreau, Vincent Ribrag, Valérie Camara-clayette, Cyril Quivoron, Gilles Salles, Sophie Cotteret, Pierre Sujobert, Alexandra Traverse-Glehen, Claire Mauduit, Pascaline Etancelin, Sarah Huet, Liana Veresezan, Krimo Bouabdallah, Marie Parrens, Audrey Gros, Samuel Amintas, David Sibon, Ludovic Lhermitte, Thomas Steimle, Sophie Kaltenbach, Bettina Fabiani, Camille Laurent, Barbara Burroni, Laurent Martin, Thierry Jo Molina, Lysa LYSARC study group, Fabrice Jardin
Journal: Blood (2020)
Combined Inhibition of CXCR4 Signaling and System xc- Transporter Activity Induces Synthetic Lethality in T-ALL Cells By Suppressing Gsh and Inducing Ferroptosis
Authors: Jun Xia, Stephanie Sun, Matthew RM Jotte, Geoffrey L Uy, Ella Sorani, Abi Vainstein, Liron Shemesh Davish, Katherine E Caldwell, William G Hawkins, Daniel C. Link
Journal: Blood (2020)
Stromal Precursors in the Bone Marrow of Untreated Patients with Severe and Non-Severe Aplastic Anemia Differ in the Proliferative Potential
Authors: Irina N. Shipounova, Alyona I. Dorofeeva, Nikolay M. Kapranov, Anton V. Luchkin, Zalina T. Fidarova, Elena A Mikhailova, Valeriy G. Savchenko
Journal: Blood (2020)
Impaired Sars-Cov-2 Specific Antibody Responses in Patients Treated with Anti-CD20 Antibodies
Authors: Alessandra Sottini, Luisa Imberti, Simone Paghera, Vanessa Previcini, Chiara Cattaneo, Eugenia Quiros-Roldan, Ruggero Capra, Giuseppe Rossi, Kerry Dobbs, Elana Shaw, Luigi D. Notarangelo, Peter Burbelo, Jeffrey Cohen
Journal: Blood (2020)
Angiosarcoma of the Abdominal Aorta After Endovascular Aneurysm Repair
Authors: Kadeem Walker, Neiladri Khan, Philip Scherer
Journal: Clinical Nuclear Medicine (2020)

Primary angiosarcomas of the aorta are rare, highly aggressive malignant tumors for which there have been limited documented cases in the medical literature. Diagnosis is challenging due to nonspecific symptomatology and imitation of common aortic pathologies. A subset of these primary aortic angiosarcoma cases is seen in association with endovascular aneurysm repair, or EVAR; however, the connection between the 2 entities is not completely understood. Here, we present 18F-FDG PET/CT imaging findings of an angiosarcoma of the aorta in a 69-year-old man status post EVAR.
Long-Term Efficacy and Safety (27 months) of the Biosimilar CT-P10 in Patients with Low Tumor Burden Follicular Lymphoma
Authors: Larry W Kwak, Juan Manuel Sancho, Seok-Goo Cho, Hideyuki Nakazawa, Junji Suzumiya, Gayane Tumyan, Jin Seok Kim, Tobias F Menne, Jose Mario Mariz, Nikolai Ilyin, Wojciech Jurczak, Aurelio Lopez Martínez, Olga Samoilova, Edvard Zhavrid, Eduardo Yanez Ruiz, Marek Trneny, Leslie L. Popplewell, Michinori Ogura, Won Seog Kim, Sang Joon Lee, Sung Hyun Kim, Keum Young Ahn, Christian Buske
Journal: Blood (2020)
Biomarker Analysis in Patients (pts) with Steroid-Refractory Acute Graft-Vs-Host Disease (aGVHD) Treated with Ruxolitinib (RUX) or Best Available Therapy (BAT) in the Randomized, Phase 3 REACH2 Study
Authors: Gérard Socié, Dietger Niederwieser, Nikolas Von Bubnoff, Mohamad Mohty, Jeffrey Szer, Reuven Or, Jason P Butler, Eva Maria Wagner, Edouard Forcade, Jaime Sanz Caballer, Domenico Russo, Giovanni Grillo, Tsila Zuckerman, Sinem Civriz Bozdag, David Ritchie, Shalini Chaturvedi, Anirudh Prahallad, Karen Sinclair, Celine Wilke, Robert Zeiser
Journal: Blood (2020)
Efficient Enucleation and In Vivo Circulation of Differentiated Human Erythroblasts Derived from Peripheral Blood Mononuclear Cells after Extensive Expansion
Authors: Senquan Liu, Mengyao Wu, Yongxing Gao, Jiusheng Deng, John D Roback, Tong Chen, Linzhao Cheng
Journal: Blood (2020)
Prognostic Impact of Metabolic Tumor Burden in Large B-Cell Lymphoma Patients Receiving CAR T-Cell Therapy
Authors: Gloria Iacoboni, Marc Simo, Guillermo Villacampa, Eva Catala, Cecilia Carpio, Candido Diaz-Lagares, Angela Vidal-Jordana, Sabela Bobillo, Ana Marin-Niebla, Ana Perez, Moraima Jiménez, Pau Abrisqueta, David Valcárcel, Francesc Bosch, Pere Barba
Journal: Blood (2020)
A Novel Next-Generation FVIII Mimetic, Mim8, Has a Favourable Safety Profile. Results from a 26-Week Safety Study in Cynomolgus Monkeys
Authors: Brian Lauritzen, Mads Bjelke, Marie Rossen, Mikala Skydsgaard, Marianne Kjalke, Olle Björkdahl, Stine L Kjellev
Journal: Blood (2020)
A subset of pediatric-type thalamic gliomas share a distinct DNA methylation profile, H3K27me3 loss and frequent alteration of <i>EGFR</i>
Authors: Philipp Sievers, Martin Sill, Daniel Schrimpf, Damian Stichel, David E Reuss, Dominik Sturm, Jürgen Hench, Stephan Frank, Lenka Krskova, Ales Vicha, Michal Zapotocky, Brigitte Bison, David Castel, Jacques Grill, Marie-Anne Debily, Patrick N Harter, Matija Snuderl, Christof M Kramm, Guido Reifenberger, Andrey Korshunov, Nada Jabado, Pieter Wesseling, Wolfgang Wick, David A Solomon, Arie Perry, Thomas S Jacques, Chris Jones, Olaf Witt, Stefan M Pfister, Andreas von Deimling, David T W Jones, Felix Sahm
Journal: Neuro-Oncology (2020)

Abstract Background Malignant astrocytic gliomas in children show a remarkable biological and clinical diversity. Small in-frame insertions or missense mutations in the epidermal growth factor receptor gene (EGFR) have recently been identified in a distinct subset of pediatric-type bithalamic gliomas with a unique DNA methylation pattern. Methods Here, we investigated an epigenetically homogeneous cohort of malignant gliomas (n = 58) distinct from other subtypes and enriched for pediatric cases and thalamic location, in comparison with this recently identified subtype of pediatric bithalamic gliomas. Results EGFR gene amplification was detected in 16/58 (27%) tumors, and missense mutations or small in-frame insertions in EGFR were found in 20/30 tumors with available sequencing data (67%; 5 of them co-occurring with EGFR amplification). Additionally, 8 of the 30 tumors (27%) harbored an H3.1 or H3.3 K27M mutation (6 of them with a concomitant EGFR alteration). All tumors tested showed loss of H3K27me3 staining, with evidence of overexpression of the EZH inhibitory protein (EZHIP) in the H3 wildtype cases. Although some tumors indeed showed a bithalamic growth pattern, a significant proportion of tumors occurred in the unilateral thalamus or in other (predominantly midline) locations. Conclusions Our findings present a distinct molecular class of pediatric-type malignant gliomas largely overlapping with the recently reported bithalamic gliomas characterized by EGFR alteration, but additionally showing a broader spectrum of EGFR alterations and tumor localization. Global H3K27me3 loss in this group appears to be mediated by either H3 K27 mutation or EZHIP overexpression. EGFR inhibition may represent a potential therapeutic strategy in these highly aggressive gliomas.
Regional differences in the incidence and outcome of acute ischemic heart failure after ST-elevation myocardial infarction in Sweden
Authors: B. Björn Redfors, S. Volz, O. Angeras, D. Ioanes, J. Odenstedt, C. Ljungman, C. Dworeck, T. Jernberg, J. Jensen, T. Ramunddal, P. Petursson, Ole Fröbert, S. James, D. Erlinge, E. Omerovic
Journal: European Journal of Heart Failure (2019)
Consensus statement on concussion in sport: the 4th International Conference on Concussion in Sport held in Zurich, November 2012
Authors: Paul McCrory, Willem H Meeuwisse, Mark Aubry, Bob Cantu, Jiří Dvořák, Ruben J Echemendia, Lars Engebretsen, Karen Johnston, Jeffrey S Kutcher, Martin Raftery, Allen Sills, Brian W Benson, Gavin A Davis, Richard G Ellenbogen, Kevin Guskiewicz, Stanley A Herring, Grant L Iverson, Barry D Jordan, James Kissick, Michael McCrea, Andrew S McIntosh, David Maddocks, Michael Makdissi, Laura Purcell, Margot Putukian, Kathryn Schneider, Charles H Tator, Michael Turner
Journal: British Journal of Sports Medicine (2013)

The new 2012 Zurich Consensus statement is designed to build on the principles outlined in the previous documents and to develop further conceptual understanding of this problem using a formal consensus-based approach. A detailed description of the consensus process is outlined at the end of this document under the Background section. This document is developed primarily for use by physicians and healthcare professionals who are involved in the care of injured athletes, whether at the recreational, elite or professional level.
The T cell CD6 receptor operates a multitask signalosome with opposite functions in T cell activation
Authors: Daiki Mori, Claude Grégoire, Guillaume Voisinne, Javier Celis-Gutierrez, Rudy Aussel, Laura Girard, Mylène Camus, Marlène Marcellin, Jérémy Argenty, Odile Burlet-Schiltz, Frédéric Fiore, Anne Gonzalez de Peredo, Marie Malissen, Romain Roncagalli, Bernard Malissen
Journal: The Journal of Experimental Medicine (2020)

To determine the respective contribution of the LAT transmembrane adaptor and CD5 and CD6 transmembrane receptors to early TCR signal propagation, diversification, and termination, we describe a CRISPR/Cas9–based platform that uses primary mouse T cells and permits establishment of the composition of their LAT, CD5, and CD6 signalosomes in only 4 mo using quantitative mass spectrometry. We confirmed that positive and negative functions can be solely assigned to the LAT and CD5 signalosomes, respectively. In contrast, the TCR-inducible CD6 signalosome comprised both positive (SLP-76, ZAP70, VAV1) and negative (UBASH3A/STS-2) regulators of T cell activation. Moreover, CD6 associated independently of TCR engagement to proteins that support its implication in inflammatory pathologies necessitating T cell transendothelial migration. The multifaceted role of CD6 unveiled here accounts for past difficulties in classifying it as a coinhibitor or costimulator. Congruent with our identification of UBASH3A within the CD6 signalosome and the view that CD6 constitutes a promising target for autoimmune disease treatment, single-nucleotide polymorphisms associated with human autoimmune diseases have been found in the Cd6 and Ubash3a genes.
Abstract 547: Hur Dependent Regulation of Inflammatory Remodeling Following Myocardial Ischemia/reperfusion Injury
Authors: Samuel F Slone, Salma Fleifil, Perwez Alam, Sarah Anthony, Michelle L Nieman, John Lorenz, Michael Tranter
Journal: Circulation Research (2020)

Myocardial infarction (MI), resulting from ischemia/reperfusion (I/R) injury due to the obstruction of coronary blood flow, affects an estimated 800,000 Americans annually resulting in a cost of nearly 12 billion dollars to the health care system. Recent medical advances have led to improved survival following acute MI, but unfortunately, the post-MI inflammatory and fibrotic remodeling of the heart is driving an increase in the prevalence of heart failure. Preliminary data from our lab shows that the RNA binding protein Human antigen R (HuR) undergoes nuclear-to-cytoplasmic translocation within 30 minutes and is increased in expression at both 2 hours and 7 days post-I/R. The objective of this work is to determine the mechanistic role of HuR on the regulation of cardiac cytokine/chemokine expression and the functional effect of HuR on macrophage infiltration and polarization post-I/R. Wild-type mice were subjected to 30 minutes of LAD (left anterior descending) coronary artery ligation (ischemia) followed by reperfusion with HuR inhibitor or vehicle control administered at the start of reperfusion. Our results show that inhibition of HuR reduces cardiac mRNA expression of IL-6, TNF-alpha, and ICAM-1 at 2 hours post-reperfusion, but does not affect initial (24 hour) infarct size. In addition, HuR inhibition reduces macrophage infiltration at 7 days post-I/R, as well as cardiac fibrosis and ventricular dilation while preserving cardiac function at 14 days post-I/R. Furthermore, H9c2s treated with HuR inhibitor blunts the mRNA expression of CCL2 after acute stimulation of lipopolysaccharide. In conclusion, we show that HuR inhibition at the time of reperfusion is protective against post-MI inflammatory and fibrotic remodeling through a reduction in inflammatory gene expression and macrophage infiltration. Previous work by the lab has demonstrated a direct role for HuR in cardiac myocytes, but these results also suggest that HuR-mediated gene expression in macrophages may play a role in post-MI inflammatory and fibrotic remodeling.
Bipotent Lymphoid Progenitors Independently Maintain Long-Term Genetically Engineered T and NK Cell Production in Humans
Authors: Natalia Izotova, Christine Rivat, Cristina Baricordi, Elena Blanco-Alvarez, Danilo Pellin, Eleanor Watt, Soragia Athina Gkazi, Stuart Adams, Kimberly Gilmour, Jinhua Xu Bayford, Claire Booth, Bobby H Gaspar, Adrian J. Thrasher, Luca Biasco
Journal: Blood (2020)
A phase III study of comparing FOLFOX+/-bevacizumab with FOLFOX+/-bevacizumab+ high-dose intravenous vitamin C as first-line therapy in patients with advanced colorectal cancer.
Authors: Feng Wang, Jian Xiao, Yan-Qiao Zhang, Xianglin Yuan, Weijia Fang, Wei Wang, Xiaohua HU, Zhixiang Zhuang, Fuxiang Zhou, Jieer Ying, Ying Yuan, Zeng-qing Guo, XiangYuan Wu, Qing-Feng Zou, Ming-ming He, Ying Guo, Shuang-Zhen Chen, Rui-hua Xu
Journal: Journal of Clinical Oncology (2020)

TPS4115 Background: Previous studies showed that high dose vitamin C especially when administered intravenously might have anti-cancer effect. A recent preclinical study found that human colorectal cancer cells harboring KRAS or BRAF mutations are selectively killed by high dose vitamin C. Our phase I dose-escalation and expansion study has shown that high dose (up to 1.5g/kg) intravenous vitamin C with FOLFOX or FOLFIRI is well tolerated in patients with colorectal or gastric cancer. This trial is a randomized, multicenter, phase Ⅲ study of high dose vitamin C infusion combined with FOLFOX +/- bevacizumab versus FOLFOX +/- bevacizumab as first-line therapy in patients with advanced colorectal cancer. Methods: This study has enrolled patients with histologically confirmed metastatic adenocarcinoma of colorectum, normal G6PD status and no prior treatment for metastatic disease. 432 patients are randomized 1:1 into one of two groups. Patients in the control group are treated with mFOLFOX6 (oxaliplatin 85 mg/m² d1 concurrent with leucovorin 400 mg/m², followed by bolus 5FU 400 mg/m² d1, followed by infusional 5FU 2400 mg/m² over 46 hours) with or without bevacizumab (5mg/kg, d1) every 2 weeks. Patients in the experimental group are treated with vitamin C intravenously (1.5g/kg/day, d1-3) in combination with mFOLFOX6 with or without bevacizumab every 2 weeks. Randomization is stratified by the location of primary site (left-sided or right-sided) and treatment with bevacizumab (with or without). The primary endpoint is progression free survival (assessed by investigator per RECIST v1.1). Secondary endpoints are overall survival, response rate, assessment of treatment-related adverse events, progression free survival and overall survival in RAS or BRAF mutant patients. Genome, microbiome and metabolome are also assessed. Clinical trial information: NCT02969681 .
The Addition of Carfilzomib to a Lenalidomide-Based Triplet Improves Outcomes in Newly Diagnosed Transplant Eligible Myeloma Patients with Renal Impairment: A Subgroup Analysis of the Myeloma XI Trial
Authors: Charlotte Pawlyn, Tom Menzies, Faith E. Davies, Ritika Rana, Jennifer Pinney, Gordon Cook, Walter Martin Gregory, Matthew W Jenner, John R Jones, Martin F. Kaiser, Roger G Owen, Gareth Morgan, Graham H Jackson, David Cairns, Mark T Drayson
Journal: Blood (2020)
Loss of ARID1A Promotes Epithelial–Mesenchymal Transition and Sensitizes Pancreatic Tumors to Proteotoxic Stress
Authors: Hideo Tomihara, Federica Carbone, Luigi Perelli, Justin K. Huang, Melinda Soeung, Johnathon L. Rose, Frederick S. Robinson, Yonathan Lissanu Deribe, Ningping Feng, Mitsunobu Takeda, Akira Inoue, Edoardo Del Poggetto, Angela K. Deem, Anirban Maitra, Pavlos Msaouel, Nizar M. Tannir, Giulio F. Draetta, Andrea Viale, Timothy P. Heffernan, Christopher A. Bristow, Alessandro Carugo, Giannicola Genovese
Journal: Cancer Research (2020)

Cellular dedifferentiation is a key mechanism driving cancer progression. Acquisition of mesenchymal features has been associated with drug resistance, poor prognosis, and disease relapse in many tumor types. Therefore, successful targeting of tumors harboring these characteristics is a priority in oncology practice. The SWItch/Sucrose non-fermentable (SWI/SNF) chromatin remodeling complex has also emerged as a critical player in tumor progression, leading to the identification of several SWI/SNF complex genes as potential disease biomarkers and targets of anticancer therapies. AT-rich interaction domain-containing protein 1A (ARID1A) is a component of SWI/SNF, and mutations in ARID1A represent one of the most frequent molecular alterations in human cancers. ARID1A mutations occur in approximately 10% of pancreatic ductal adenocarcinomas (PDAC), but whether these mutations confer a therapeutic opportunity remains unclear. Here, we demonstrate that loss of ARID1A promotes an epithelial-mesenchymal transition (EMT) phenotype and sensitizes PDAC cells to a clinical inhibitor of HSP90, NVP-AUY922, both in vitro and in vivo. Although loss of ARID1A alone did not significantly affect proliferative potential or rate of apoptosis, ARID1A-deficient cells were sensitized to HSP90 inhibition, potentially by promoting the degradation of intermediate filaments driving EMT, resulting in cell death. Our results describe a mechanistic link between ARID1A defects and a quasi-mesenchymal phenotype, suggesting that deleterious mutations in ARID1A associated with protein loss exhibit potential as a biomarker for patients with PDAC who may benefit by HSP90-targeting drugs treatment. SIGNIFICANCE: This study identifies ARID1A loss as a promising biomarker for the identification of PDAC tumors that are potentially responsive to treatment with proteotoxic agents.
Differential Acetone Extraction of Total and Hemoprotein-Unbound Heme to Quantify Heme Binding Capacity of Plasma in Patients with Sickle Cell Disease: The Role of Heme Scavengers
Authors: Madhav Vissa, Eric Soupene, Sandra K. Larkin, Lynne D. Neumayr, Elliott P. Vichinsky, Frans A. Kuypers
Journal: Blood (2020)
Exosomal MiR-107 As Novel Biomarker and Tumor Suppressor By Targeting Ywhah in Diffuse Large B-Cell Lymphoma
Authors: Jiarui Liu, Yang Han, Shunfeng Hu, Linquan Zhan, Xinting Hu, Juan Yang, Shuai Ren, Yiqing Cai, Xin Wang, Xiangxiang Zhou
Journal: Blood (2020)
Heterogeneity of Hematopoietic Stem and Progenitor Cell (HSPC) Composition in Αβ T-Cell/CD19 B-Cell Depleted Peripheral Blood Cell Stem Cell (PBSC) Transplant Grafts and Correlation with Immune and Hematopoietic Recovery
Authors: Giulia Barbarito, Beruch Dejene, David C Shyr, Gopin Saini, Linda Oppizzi, Sruthi Mantri, Hye-Sook Kwon, Matthew H. Porteus, Kenneth I. Weinberg, Alice Bertaina
Journal: Blood (2020)
Abstract 246: YAP1 Activation Suppresses Heart Failure Through Regulation of DNA Repair
Authors: Jianming Jiang, Chia Yee Tan
Journal: Circulation Research (2020)

Introduction: The mammalian hearts including humans have a limited regenerative capacity. Activation of proliferation or related signaling pathways has been shown to reinstate cell renewal capacity of cardiomyocytes (CM) which is believed to ameliorate heart failure (HF). However, whether new CM are generated underlying cardiac regeneration in adult mammalian hearts upon damage is elusive. It is also unknown whether and by what mechanisms activation of CM proliferation benefits HF besides cardiac regeneration. Hypothesis: The protective role of cardiac cell cycle activation for damaged hearts could be independent of heart regeneration. Methods and Results: We show that cardiac specific activation of YAP1 , the terminal effector of the Hippo signaling pathway, suppressed HF and cardiac fibrosis induced by Lmna insufficiency ( Lmna HF). Although activation of YAP1 promoted G1 and S phase of cardiac cell cycle in disease hearts, CM did not undergo mitotic phase, a critical step for heart regeneration. RNAseq followed by signaling pathway analysis and validation showed that Fanconi anemia (FA) DNA repair pathway was activated by YAP1 . Cardiac DNA damage in Lmna HF was suppressed by YAP1 activation. Importantly, reduction of Fancd2 compromised the suppressive role of YAP1 in Lmna HF. Mechanistically, YAP1 promoted mono-ubiquitination of FANCD2 (ub-FANCD2) through promoting cell cycle. Conclusions: Our findings demonstrate that promoting cardiac DNA repair becomes a new therapeutic strategy against HF.
c-Rel orchestrates energy-dependent epithelial and macrophage reprogramming in fibrosis
Authors: Jack Leslie, Marina García Macia, Saimir Luli, Julie C. Worrell, William J. Reilly, Hannah L. Paish, Amber Knox, Ben S. Barksby, Lucy M. Gee, Marco Y. W. Zaki, Amy L. Collins, Rachel A. Burgoyne, Rainie Cameron, Charlotte Bragg, Xin Xu, Git W. Chung, Colin D. A. Brown, Andrew D. Blanchard, Carmel B. Nanthakumar, Morten Karsdal, Stuart M. Robinson, Derek M. Manas, Gourab Sen, Jeremy French, Steven A. White, Sandra Murphy, Matthias Trost, Johannes L. Zakrzewski, Ulf Klein, Robert F. Schwabe, Ingmar Mederacke, Colin Nixon, Tom Bird, Laure-Anne Teuwen, Luc Schoonjans, Peter Carmeliet, Jelena Mann, Andrew J. Fisher, Neil S. Sheerin, Lee A. Borthwick, Derek A. Mann, Fiona Oakley
Journal: Nature Metabolism (2020)
A phase 1b study of once‐weekly carfilzomib combined with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma
Authors: Melissa Alsina, Ola Landgren, Noopur Raje, Ruben Niesvizky, William I. Bensinger, Jesus G. Berdeja, Tibor Kovacsovics, David H. Vesole, Belle Fang, Amy S. Kimball, David S. Siegel
Journal: American Journal of Hematology (2020)

Twice-weekly carfilzomib with lenalidomide-dexamethasone (Rd) is an effective regimen for newly diagnosed multiple myeloma (NDMM). Here we evaluated once-weekly carfilzomib with Rd (once-weekly KRd) in NDMM patients. The NDMM patients were enrolled regardless of transplant eligibility. Patients received carfilzomib on days 1, 8, and 15; lenalidomide 25 mg on days 1-21; and dexamethasone 40 mg on carfilzomib days (also day 22 for cycles 1-8) for ≤18, 28-day cycles. Enrollment initiated in a carfilzomib 20/70 mg/m2 (20 mg/m2 on cycle one, day 1; 70 mg/m2 thereafter) NDMM dose-expansion arm, which was suspended because of serious adverse events. After evaluation of dose-limiting toxicities in a two-step-up dose-evaluation cohort, an NDMM dose-expansion arm (carfilzomib 20/56 mg/m2 ) was opened. Fifty-one NDMM patients were enrolled in dose-finding and dose-expansion cohorts. Results are presented for the carfilzomib 56 mg/m2 NDMM dose-expansion arm (n = 33). The grade ≥ 3 treatment-emergent AE (TEAE) rate was 63.6%. Twenty-five patients underwent stem cell collection; 18 proceeded to auto stem cell transplant, and five resumed KRd on study after autoSCT. The overall response rate (ORR) based on best overall response by cycle four was 97.0% (≥very good partial response [VGPR], 69.7%) in the NDMM 20/56 mg/m2 cohort. In patients who did not receive autoSCT (n = 15), the median number of cycles was 16.0; ORR was 93.3% (≥VGPR, 80.0%). At a median follow-up of 8.1 months, median progression-free survival was not reached. Once-weekly KRd (carfilzomib 56 mg/m2 ) had a favorable safety profile and promising activity in NDMM, supporting the use of this regimen in this setting.