tbuckley/cabot-search huggingface dataset:
Abstract 199: TGF-β in exosomes facilitates HNSCC progression by accelerating tumor angiogenesis
Authors: Nils Ludwig, Saigopalakrishna S. Yerneni, Cynthia S. Hinck, Monika Pietrowska, Andrew P. Hinck, Theresa L. Whiteside
Journal: Cancer Research (2019)

Abstract TGF-β is a key regulator for tumor initiation and progression in head and neck squamous cell carcinoma (HNSCC). Tumor-derived exosomes (TEX) contain TGF-β and accumulate in the tumor microenvironment (TME). This study characterizes the TGF-β content of HNSCC-derived exosomes and evaluates in vitro and in vivo TGF-β signaling by exosomes that results in promotion of angiogenesis. TEX were isolated from supernantants of 5 different HNSCC cell lines by mini size exclusion chromatography (mini-SEC) and characterized by electron microscopy, nanoparticle tracking analysis and mass spectrometry (LC-MS/MS). TGF-β content in exosomes was evaluated by immunoblotting. Proliferation and migration of SVEC4-10 lymphendothelial cells in response to TEX were investigated in vitro and results were confirmed in vivo, using a matrigel plug model in mice. In these experiments a novel trivalent TGF-β receptor trap (mRER) was used to inhibit TGF-β signaling. TGF-β levels and activity were similarly measured in exosomes isolated from plasma of 20 HNSCC patients. TEX carried high levels of TGF-β and were found to be potent inducers of angiogenesis in vitro and in vivo through functional reprogramming and phenotypic modulation of endothelial cells. Proliferation (p&amp;lt;0.01) and migration (p&amp;lt;0.01) by SVEC4-10 were stimulated by TEX and effects were inhibited by mRER treatment of SVEC4-10 (p&amp;lt;0.05). TEX promoted formation of defined vascular structures in vivo, and increased (p&amp;lt;0.001) vascularization in matrigel plugs relative to control. Those effects were inhibited by mRER treatment (p&amp;lt;0.05). Exosomes in plasma of HNSCC patients carried varying levels of TGF-β, and patients with nodal metastases had elevated TGF-β levels (p&amp;lt;0.01) relative to patients with no meastasis.The data show that TGF-β signaling by TEX in HNSCC promotes angiogenesis and drives tumor progression. Future efforts should focus on silencing TEX, thereby adding new options to existing anti-angiogenic therapies. Citation Format: Nils Ludwig, Saigopalakrishna S. Yerneni, Cynthia S. Hinck, Monika Pietrowska, Andrew P. Hinck, Theresa L. Whiteside. TGF-β in exosomes facilitates HNSCC progression by accelerating tumor angiogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 199.
Abstract 20615: Trends in Outcomes Associated With Percutaneous Coronary Interventions on Bifurcation Lesions
Authors: Sopan Lahewala, Nirali Patel, Prashant Patel, Byomesh Tripathi, Mihir Dave, Varun Kumar, Smit Patel, Priti Malik, Harshil Shah, Shilpkumar Arora, Amer Syed, Apurva Badheka
Journal: Circulation (2017)

Introduction: Bifurcation lesions present major percutaneous coronary interventional challenge. Data on outcomes in bifurcation lesion appears sparse and hence here we seek to evalute the procedura...
Abstract 2136: Doublecortin-like Kinase 1 (DCLK1) correlates with the cell proliferation in malignant pleural mesothelioma
Authors: Akihiro Miura, Hiromasa Yamamoto, Hiroyuki Tao, Ken Suzawa, Syunsaku Miyauchi, Kota Araki, Yuta Takahashi, Eisuke Kurihara, Yusuke Ogoshi, Kazuhiko Shien, Junichi Soh, Kazunori Okabe, Shuta Tomida, Masakiyo Sakaguchi, Shinichi Toyooka
Journal: Cancer Research (2019)

Abstract Background: Malignant pleural mesothelioma (MPM) is a refractory disease with poor prognosis despite multimodality therapy. Because standard therapy is unsatisfactory, it is expected to establish a novel strategy such as molecular-targeting therapy for MPM. Doublecortin-like kinase 1 (DCLK1), a microtubule-associated protein, is one of the tumor-specific stem cell marker and is revealed that the cell survival is reduced by inhibiting this protein in pancreatic and colorectal cancers. DCLK1 is known to have several isoforms named as isoform #1-#4, although the significance of them in MPM has not been clarified. We hypothesized that DCLK1 was a potential therapeutic target for MPM.&amp;lt;Materials and Methods: Immunohistochemical staining was performed using surgically resected formalin-fixed paraffin-embedded tissue of MPM to evaluate the expression of DCLK1. Additionally, MPM cell lines were analyzed to characterize the protein and mRNA expression of DCLK1 by western blotting and RT-PCR. The expression of DCLK1 isoforms were selectively knocked down by small interfering RNA (siRNA) and cell viability was analyzed by colony formation and cell count assays. Results: Immunohistochemical staining demonstrated that the expression of DCLK1 in MPM specimens was positive in 24 out of 27 samples (89%). Western blotting and RT-PCR revealed that DCLK1 was expressed in seven out of nine MPM cell lines. The results of RT-PCR revealed that isoform #2 and isoform #4 of DCLK1 were expressed in H2052, isoform #4 was expressed in H28, and isoform #2 was expressed in YUMC44 cell lines. Expressions of DCLK1 isoforms were selectively suppressed by isoform-specific siRNAs. Colony formation and cell count assays revealed that siRNA-mediated knockdown of both isoforms #2 and #4 suppressed cell growth compared to knockdown by negative control siRNA and knockdown of only isoform #2 or #4. Conclusion: Our results demonstrate that simultaneous knockdown of both isoforms #2 and #4of DCLK1 results in the inhibition of cell growth and suggest its potential as a therapeutic target in MPM. Citation Format: Akihiro Miura, Hiromasa Yamamoto, Hiroyuki Tao, Ken Suzawa, Syunsaku Miyauchi, Kota Araki, Yuta Takahashi, Eisuke Kurihara, Yusuke Ogoshi, Kazuhiko Shien, Junichi Soh, Kazunori Okabe, Shuta Tomida, Masakiyo Sakaguchi, Shinichi Toyooka. Doublecortin-like Kinase 1 (DCLK1) correlates with the cell proliferation in malignant pleural mesothelioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2136.
Clinical, pathological, and prognostic features of rare BRAF mutations in metastatic colorectal cancer: a bi-institutional retrospective analysis (REBUS study)
Authors: M. Bensi, M. Calegari, M. Basso, A. Orlandi, A. Boccaccino, F. Lombardo, I. Zurlo, B. Di Stefano, F. Camarda, R. Vivolo, A. Cocomazzi, M. Martini, A. Auriemma, C. Pozzo, E. Bria, L. Salvatore, G. Tortora
Journal: Annals of Oncology (2019)
Abstract 4232: Spatially constrained tumor growth affects the patterns of clonal selection and neutral drift in cancer genomic data
Authors: Kate Chkhaidze, Timon Heide, Benjamin Werner, Marc J. Williams, Weini Huang, Giulio Caravagna, Ann-Marie Baker, Trevor A. Graham, Andrea Sottoriva
Journal: Cancer Research (2019)

Abstract Quantification of the effect of spatial tumor sampling on the patterns of mutations detected in next-generation sequencing data is largely lacking. Here we use a spatial stochastic cellular automaton model of tumor growth that accounts for somatic mutations, selection, drift and spatial constrains, to simulate multi-region sequencing data derived from spatial sampling of a neoplasm. We show that the spatial structure of a solid cancer has a major impact on the detection of clonal selection and genetic drift from bulk sequencing data and single-cell sequencing data. Our results indicate that spatial constrains can introduce significant sampling biases when performing multi- region bulk sampling and that such bias becomes a major confounding factor for the measurement of the evolutionary dynamics of human tumors. We present a statistical inference framework that takes into account the spatial effects of a growing tumor and allows inferring the evolutionary dynamics from patient genomic data. Our analysis shows that measuring cancer evolution using next-generation sequencing while accounting for the numerous confounding factors requires a mechanistic model-based approach that captures the sources of noise in the data. Citation Format: Kate Chkhaidze, Timon Heide, Benjamin Werner, Marc J. Williams, Weini Huang, Giulio Caravagna, Ann-Marie Baker, Trevor A. Graham, Andrea Sottoriva. Spatially constrained tumor growth affects the patterns of clonal selection and neutral drift in cancer genomic data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4232.
Abstract 2751: Development of a specific Wee-1 inhibitor
Authors: Mandy Watson, Tom Pesnot, Andrew Scott, Anthony Huxley, Gary Nelson, Montserrat Shelbourne, Jen Morton, Tilly Bingham
Journal: Cancer Research (2019)

Abstract Somatic mutations in the TP53 gene are one of the most frequent alterations in human cancers. The resulting TP53-deficient cancer cells rely on WEE1 to trigger a G2/M arrest, which allows for DNA repair and survival. Inhibition of WEE1 has therefore emerged as an attractive therapeutic strategy to selectively sensitise TP53-deficient tumours to DNA damaging agents. The WEE1 kinase inhibitor adavosertib is the only agent undergoing evaluation in a range of clinical trials to validate this hypothesis. It has also been the tool compound of choice to interrogate WEE1 biology for over a decade. However, recent reports show adavosertib has antiproliferative single agent activity, which is counter intuitive considering its postulated mode of action. Other studies suggest adavosertib exerts poor kinase selectivity, and inhibits PLK1 with similar potency as WEE1. Since PLK1 is a well-established mitotic regulator with biological functions throughout the cell cycle, its inhibition may contribute to the clinical efficacy and toxicity observed for adavosertib. Other reported WEE1 inhibitors also suffer from low selectivity and single agent toxicity, making then unsuitable tool compounds. There is a clear need to identify a selective Wee1 tool compound. Using a structure-based drug design approach, we exploited subtle active site differences to identify novel, potent WEE1 inhibitors that display high selectivity over PLK1. These compounds allowed us to demonstrate the distinct effects of WEE1 and PLK1 inhibition on cellular toxicity, and confirm that adavosertib’s single agent efficacy is unlikely to be mediated solely through the inhibition of WEE1. Our ongoing studies aim to provide a WEE1 selective tool compound that more rigorously probes WEE1 biology, and eventually leads to the development of less toxic therapeutic agents. Citation Format: Mandy Watson, Tom Pesnot, Andrew Scott, Anthony Huxley, Gary Nelson, Montserrat Shelbourne, Jen Morton, Tilly Bingham. Development of a specific Wee-1 inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2751.
Concerns About Direct-Acting Antiviral Agents for Hepatitis C—Cause for Reassurance
Authors: Lauren A. Beste
Journal: JAMA Network Open (2019)

Elizabeth A. McGlynn, PhD; John L. Adams, PhD; Jason Kramer, MS; Amandeep K. Sahota, MD; Michael J. Silverberg, PhD; Elizabeth Shenkman, MD; David R. Nelson, MD
Abstract 2058: BCL-2 selective inhibitor APG-2575 synergizes with BTK inhibitor in preclinical xenograft models of follicular lymphoma and diffuse large B-cell lymphoma
Authors: Douglas D. Fang, Guoqin Zhai, Shoulai Gu, Ran Tao, Qiuqiong Tang, Ping Min, Qixin Wang, Dongmei Yang, Jiaxing Gu, Yinfeng Li, Dingxiong Chen, Jiajun Li, Guangfeng Wang, Dajun Yang, Yifan Zhai
Journal: Cancer Research (2019)

Abstract Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are among the most prevalent B-lymphocyte neoplasms with Bruton’s tyrosine kinase (BTK) often found abnormally activated in these patients. BTK inhibitor ibrutinib has showed proven efficacy in both indications, but its clinical application is limited to gradually acquired resistance. Recent studies reported that ibrutinib-resistant cells exhibited higher BCL-2 expression and therefore increase their sensitivity to BCL-2 inhibitors. In this study, using a BCL-2 selective inhibitor APG-2575, we asked whether its combination with ibrutinib enhanced antitumor activity in FL and DLBCL in preclinical studies. Indeed, the combination treatment with APG-2575 and ibrutinib synergistically enhanced antitumor activity in DOHH2 cell-derived FL xenograft models. Similarly, enhanced activity was achieved in DLBCL xenograft models derived from OCI-LY1 cells. Interestingly, in OCI-LY1 xenografts, the combination treatment achieved a 100 % response rate, which include partially (PR) and complete tumor regression (CR), with ~80 % of CR and ~20 % of PR recorded. Durable response was continuously observed till the end of the study after dose suspension. Pharmacokinetic studies revealed that there were no significant changes in drug concentrations between single agents and the combination treatment, suggesting there was no drug-drug interaction between these two agents. On-target pharmacodynamic (PD) modulations of BTK and apoptosis pathways were observed in corresponding tumor tissues co-treated with ibrutinib and APG-2575. An increase in the levels of cleaved PARP-1 protein was observed under the combination treatment suggesting enhanced induction of apoptosis occurred, which may be the biological event contributing to the synergistic effect of the combination treatment. In summary, our study suggests that APG-2575 may be applied to the combination therapy with ibrutinib in the treatment of FL and DLBCL. Citation Format: Douglas D. Fang, Guoqin Zhai, Shoulai Gu, Ran Tao, Qiuqiong Tang, Ping Min, Qixin Wang, Dongmei Yang, Jiaxing Gu, Yinfeng Li, Dingxiong Chen, Jiajun Li, Guangfeng Wang, Dajun Yang, Yifan Zhai. BCL-2 selective inhibitor APG-2575 synergizes with BTK inhibitor in preclinical xenograft models of follicular lymphoma and diffuse large B-cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2058.
A traditional hip implant is as effective as newer types for people over 65
Authors: Rob Cook, Tara Lamont, Rosie Martin
Journal: BMJ (2019)

The study Fawsitt C, Thom H, Hunt L. Choice of prosthetic implant combinations in total hip replacement: cost-effectiveness analysis using UK and Swedish hip joint registries data. Value Health 2019;22:303-12. This study was funded by the NIHR Research for Patient Benefit Programme (project number PB-PG-0613-31032). To read the full NIHR Signal, go to https://discover.dc.nihr.ac.uk/content/signal-000771/a-traditional-hip-implant-is-as-effective-as-more-expensive-newer-types-for-older-people
Abstract 13907: Effects of Simvastatin on Arterial Stiffness are Transient: A Randomized Controlled Trial
Authors: Adam D Gepner, Karen Lazar, Claudia Korcarz, Sanjay Asthana, James H Stein, Cynthia Carlsson
Journal: Circulation (2017)

Background: Although statins improve endothelial function, their effects on arterial stiffness and aortic blood pressure in middle-aged adults are inconsistent. Methods: This was a prospective, ran...
Abstract 2141: Mechanistic studies of altertoxin II: A fungal metabolite with selective activity against Ewing sarcoma
Authors: Andrew J. Robles, Wentao Dai, Robert H. Cichewicz, Susan L. Mooberry, Peter J. Houghton
Journal: Cancer Research (2019)

Abstract Ewing sarcomas (ES) are bone and soft tissue tumors that affect children and adolescents. These cancers are driven by chromosomal translocations that most frequently result in expression of the abnormal EWSR1-FLI1 fusion protein, a transcriptional activator and modulator of RNA splicing, or similar fusion proteins. Despite significant advances in therapies for pediatric hematological malignancies over the past 30 years, there has been less progress in the development of curative therapies for advanced or metastatic pediatric solid tumors. Approximately 35% of ES are resistant to standard-of-care chemotherapeutic agents, and nearly 70% of ES patients with metastatic disease at the time of diagnosis die within 5 years. Therefore, there is a need to develop new, targeted therapies for ES that improve patient survival and decrease toxicity. We performed high-content phenotypic screens of natural product libraries to identify compounds with selective actions against pediatric solid tumor types and found that the fungal metabolite altertoxin II (ATXII) has highly selective cytotoxic activity against 6 ES cells lines compared to a panel of other pediatric and adult cancer cell lines. On average, the IC50 of ATXII is 94-fold higher (range 16- to 400-fold) in rhabdomyosarcoma (RMS) cells than in ES cells, indicating high selectivity for ES. Mechanistic studies were conducted to determine this compound’s mechanisms of actions in ES cells, with the goal of identifying new molecular targets for the treatment of ES. We found that 100 nM ATXII, a concentration that has no effect on RMS cell viability, induces cell cycle accumulation in ES cells in the S and G2/M phases, and rapid phosphorylation of histone H2A.X (gamma-H2A.X) and checkpoint kinase 1, suggesting ATXII selectively induces cell cycle arrest and DNA damage in ES cells. To determine if ES sensitivity to ATXII is a dominant or recessive phenotype, we hybridized sensitive EW8 cells (ES) with resistant Rh30 cells (RMS) and determined the sensitivity of these hybrids to ATXII. Five single-cell subclones derived from these hybrids were resistant to ATXII, suggesting that sensitivity to ATXII is a recessive phenotype in ES cells. Ongoing studies are aimed at determining the cellular uptake and binding kinetics of radiolabeled ATXII and identifying genes that mediate sensitivity and resistance to this compound by performing a genome-wide CRISPR/Cas9 knockout screen. Citation Format: Andrew J. Robles, Wentao Dai, Robert H. Cichewicz, Susan L. Mooberry, Peter J. Houghton. Mechanistic studies of altertoxin II: A fungal metabolite with selective activity against Ewing sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2141.
Abstract 2935: Novel combination of repurposed drugs induces complete cell invasion arrest of glioblastoma in vitro
Authors: Liliana Oancea-Castillo, Kerstin Bahr, Anne Régnier-Vigouroux, Maximilian Ackermann, Isaac R. Gabriel, Samuel T. Pereles, Madeleine M. Li, Dana W. Lowitt, William W. Li, Vincent W. Li
Journal: Cancer Research (2019)

Abstract Introduction: Glioblastoma multiforme (GBM) is an aggressive and lethal cancer with a poor prognosis even after conventional treatment (surgery, radiation, chemotherapy). Temozolomide (TMZ) is a standard cyotoxic agent used, despite resistance leading to recurrence. Therefore, additional strategies for targeting the tumor environment are needed. We demonstrate a combination of approved drugs (CAD) repurposed to target GBM leads to complete arrest of GBM cell invasion. Each drug in the combination individually targets diverse tumor pathways: 1) invasion via MMP2 (doxycycline); 2) angiogenesis, inflammation, and proliferation via p53-dependent G1 cell-cycle arrest (celecoxib); 3) autophagy (tamoxifen); 4) tumor metabolism and angiogenesis (metformin). Material and Methods: Multicellular Tumor Cell Spheroids (MTCS) were generated from two GBM cell lines (LN18, U87MG) and embedded in collagen (three-dimensional in vitro assay) and mixed with the drug combination at 2 doses + TMZ. GBM cell invasion was monitored and quantified over 96h. Flow cytometry analysis using Propidium-Iodine was performed (24h, 48h, 7h2 and 96h) to quantify the effect of the drug cocktail. Scanning Electron Microscopy (SEM) of MTCS was used to evaluate cell death at the ultrastructural level (96h after treatment). Results: The CAD induced complete cell invasion arrest in both U87MG and LN18 MTCS regardless of drug dose or presence of TMZ. GBM cell death was observed after 96h. TMZ in combination with CAD showed a significant increase in cell death, suggesting synergism. SEM images demonstrated large-scale changes in the tumor spheroid morphology showing GBM cell death. Conclusions: The combination of approved drugs (CAD) with TMZ can effectively halt GBM cell invasion and induce cell death in vitro. These results suggest a sensitizing effect of CAD to potentiate TMZ’s effects. Because CAD components have well established safety profiles, further investigation to define the anti-GBM mechanisms and effects on the tumor microenvironment are warranted. This CAD has potential for future therapeutic approaches. The generic nature of the drugs makes CAD an intriguing cost-effective GBM adjunctive therapy. Citation Format: Liliana Oancea-Castillo, Kerstin Bahr, Anne Régnier-Vigouroux, Maximilian Ackermann, Isaac R. Gabriel, Samuel T. Pereles, Madeleine M. Li, Dana W. Lowitt, William W. Li, Vincent W. Li. Novel combination of repurposed drugs induces complete cell invasion arrest of glioblastoma in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2935.
Phase 3 randomized study of daratumumab (DARA) + bortezomib/thalidomide/dexamethasone (D-VTd) vs VTd in transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM): CASSIOPEIA Part 1 results.
Authors: Philippe Moreau, Michel Attal, Cyrille Hulin, Marie-Christine Béné, Annemiek Broijl, Denis Caillot, Michel Delforge, Thomas Dejoie, Thierry Facon, Jérôme Lambert, Xavier Leleu, Margaret Macro, Aurore Perrot, Sonja Zweegman, Tahamtan Ahmadi, Christopher Chiu, Lixia Pei, Jessica Vermeulen, Herve Avet-Loiseau, Pieter Sonneveld
Journal: Journal of Clinical Oncology (2019)

8003 Background: VTd is a standard of care (SoC) for TE NDMM. CD38 mAb DARA significantly reduced the risk of progression/death and improved CR and MRD-negative rates in relapsed refractory MM or transplant-ineligible NDMM in phase 3 studies. We report the primary and final analysis of Part 1 of CASSIOPEIA. Methods: In Part 1, TE NDMM pts 18-65 y were randomized 1:1 to VTd (6 28-day cycles [C; 4 pre-ASCT induction, 2 post-ASCT consolidation] of V 1.3 mg/m 2 SC BIW Week [W] 1-2; T 100 mg PO QD; d 40-80 mg/week PO or IV W 1-4 C 1-2, W 1-3 C 3-6) ± DARA (16 mg/kg IV QW C 1-2, Q2W C 3-6). Melphalan 200 mg/m 2 was pre-ASCT HDT. The primary endpoint, post-consolidation sCR rate, was assessed at Day [D] 100 post-ASCT. Part 2 (maintenance) is ongoing. Results: A cohort of 1085 pts (D-VTd, 543; VTd, 542) was randomized. The D 100 post-ASCT sCR rate was significantly higher for D-VTd vs VTd (28.9% vs 20.3%; P = 0.0010; Table). At 18.8-mo median follow-up, PFS from first randomization favored D-VTd with HR 0.47 (95% CI, 0.33-0.67; P &lt;0.0001). With median PFS NR in either arm, 18-mo PFS rates were 92.7% vs 84.6% for D-VTd vs VTd. Rates of ≥CR, ≥VGPR, and MRD negativity supported sCR results (Table). OS is immature with 46 deaths on study (D-VTd, 14; VTd, 32; HR, 0.43; 95% CI, 0.23-0.80). The most common (≥10%) grade 3/4 TEAEs (D-VTd/VTd) were neutropenia (27.6%/14.7%), lymphopenia (17.0%/9.7%), stomatitis (12.7%/16.4%), and thrombocytopenia (11.0%/7.4%). In the D-VTd arm, infusion-related reactions occurred in 35.4% of pts. Conclusions: D-VTd in induction prior to and consolidation after ASCT improved depth of response (sCR, ≥CR, and MRD negativity) and PFS with acceptable safety. The favorable benefit-risk profile supports the use of D-VTd in TE NDMM. CASSIOPEIA is the first study to demonstrate clinical benefit of DARA + SoC in TE NDMM. Clinical trial information: NCT02541383. [Table: see text]