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1. Multi-objective Group Decision and Cooperative Planning Based on Preference and Fuzzy Measure

Author

Ma, Xiwen, Xie, Wei, Yang, Jingsong, Zhang, Weidong, Lu, Jinhui, Angrisani, Leopoldo, Series Editor, Arteaga, Marco, Series Editor, Chakraborty, Samarjit, Series Editor, Chen, Shanben, Series Editor, Chen, Tan Kay, Series Editor, Dillmann, Rüdiger, Series Editor, Duan, Haibin, Series Editor, Ferrari, Gianluigi, Series Editor, Ferre, Manuel, Series Editor, Hirche, Sandra, Series Editor, Jabbari, Faryar, Series Editor, Jia, Limin, Series Editor, Kacprzyk, Janusz, Series Editor, Khamis, Alaa, Series Editor, Kroeger, Torsten, Series Editor, Li, Yong, Series Editor, Liang, Qilian, Series Editor, Martín, Ferran, Series Editor, Ming, Tan Cher, Series Editor, Minker, Wolfgang, Series Editor, Misra, Pradeep, Series Editor, Mukhopadhyay, Subhas, Series Editor, Ning, Cun-Zheng, Series Editor, Nishida, Toyoaki, Series Editor, Oneto, Luca, Series Editor, Panigrahi, Bijaya Ketan, Series Editor, Pascucci, Federica, Series Editor, Qin, Yong, Series Editor, Seng, Gan Woon, Series Editor, Speidel, Joachim, Series Editor, Veiga, Germano, Series Editor, Wu, Haitao, Series Editor, Zamboni, Walter, Series Editor, Tan, Kay Chen, Series Editor, Yu, Jianglong, editor, Liu, Yumeng, editor, and Li, Qingdong, editor

Published
2024
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2. ESCCAL-1 promotes cell-cycle progression by interacting with and stabilizing galectin-1 in esophageal squamous cell carcinoma.

Author

Cui, Yuanbo, Yan, Ming, Wu, Wei, Lv, Pengju, Wang, Jinwu, Huo, Yanping, Lou, Yanan, Ma, Xiwen, Chang, Jing, Guan, Fangxia, and Cao, Wei

Abstract

Long non-coding RNAs (LncRNAs) play important roles in the development of human esophageal squamous cell carcinoma (ESCC). Our previous studies have shown that knockdown of LncRNA ESCCAL-1 expression inhibits the growth of ESCC cells, but the mechanisms remain largely unknown. In this study, we show that over-expression of ESCCAL-1 promotes ESCC cell proliferation and cell-cycle progression by blocking ubiquitin-mediated degradation of an oncoprotein galectin-1 (Gal-1). Multiple LncRNA expression datasets as well as our own data together reveal that ESCCAL-1 is evidently up-regulated in ESCC tissues and exhibits promising diagnostic value. Over-expression of ESCCAL-1 augmented ESCC cell proliferation and cell-cycle progression, whereas down-regulation of ESCCAL-1 resulted in the opposite effects. Mechanistically, LncRNA ESCCAL-1 directly binds to Gal-1 and positively regulates its protein level without affecting its mRNA level. Up-regulation of Gal-1 facilitated ESCC cell proliferation and cell-cycle progress. Knockdown of Gal-1 mitigated the effects of ESCCAL-1-mediated high cellular proliferation, NF-κB signaling activation and tumorigenicity of ESCC cells. Thus, our findings provide novel insight into the mechanism by which ESCCAL-1 facilitates ESCC tumorigenesis and cell-cycle progression by interacting with and stabilizing Gal-1 protein, suggesting a potential therapeutic target for ESCC.

Published
2022

6. Effect of Prior Therapy and Disease Refractoriness on the Efficacy and Safety of Oral Selinexor in Patients with Diffuse Large B-cell Lymphoma (DLBCL): A Post-hoc Analysis of the SADAL Study

Author

Schuster, Michael, Zijlstra, Josée, Casasnovas, Rene-Olivier, Vermaat, Joost S.P, Kalakonda, Nagesh, Goy, Andre, Choquet, Sylvain, Neste, Eric Van Den, Hill, Brian, Thieblemont, Catherine, Cavallo, Federica, De la Cruz, Fatima, Kuruvilla, John, Hamad, Nada, Jaeger, Ulrich, Caimi, Paolo, Gurion, Ronit, Warzocha, Krzysztof, Bakhshi, Sameer, Sancho, Juan-Manuel, Follows, George, Egyed, Miklos, Offner, Fritz, Vassilakopoulos, Theodoros, Samal, Priyanka, Ku, Matthew, Ma, Xiwen, Corona, Kelly, Chamoun, Kamal, Shah, Jatin, Shacham, Sharon, Kauffman, Michael G., Canales, Miguel, and Maerevoet, Marie

Published
2022
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9. Comparison of the Effectiveness and Safety of the Oral Selective Inhibitor of Nuclear Export, Selinexor, in Diffuse Large B Cell Lymphoma Subtypes

Author

Casasnovas, Rene-Olivier, Follows, George, Zijlstra, Josee M., Vermaat, Joost S.P., Kalakonda, Nagesh, Choquet, Sylvain, Neste, Eric Van Den, Hill, Brian, Thieblemont, Catherine, Cavallo, Federica, la Cruz, Fatima De, Kuruvilla, John, Hamad, Nada, Jaeger, Ulrich, Caimi, Paolo F., Gurion, Ronit, Warzocha, Krzysztof, Bakhshi, Sameer, Sancho, Juan-Manuel, Schuster, Michael, Egyed, Miklos, Offner, Fritz, Vassilakopoulos, Theodoros P., Samal, Priyanka, Ku, Matthew, Ma, Xiwen, Chamoun, Kamal, Shah, Jatin, Canales, Miguel, Maerevoet, Marie, Shacham, Sharon, Kauffman, Michael G., and Goy, Andre

Published
2022
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11. Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial

Author

Kalakonda, Nagesh, Maerevoet, Marie, Cavallo, Federica, Follows, George, Goy, Andre, Vermaat, Joost S P, Casasnovas, Olivier, Hamad, Nada, Zijlstra, Josée M, Bakhshi, Sameer, Bouabdallah, Reda, Choquet, Sylvain, Gurion, Ronit, Hill, Brian, Jaeger, Ulrich, Sancho, Juan Manuel, Schuster, Michael, Thieblemont, Catherine, De la Cruz, Fátima, Egyed, Miklos, Mishra, Sourav, Offner, Fritz, Vassilakopoulos, Theodoros P, Warzocha, Krzysztof, McCarthy, Daniel, Ma, Xiwen, Corona, Kelly, Saint-Martin, Jean-Richard, Chang, Hua, Landesman, Yosef, Joshi, Anita, Wang, Hongwei, Shah, Jatin, Shacham, Sharon, Kauffman, Michael, Van Den Neste, Eric, and Canales, Miguel A

Published
2020
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13. Survival among patients with relapsed/refractory diffuse large B cell lymphoma treated with single-agent selinexor in the SADAL study

Author

Maerevoet, Marie, Zijlstra, Josee M., Follows, George, Casasnovas, Rene-Olivier, Vermaat, J. S. P., Kalakonda, Nagesh, Goy, Andre, Choquet, Sylvain, Van Den Neste, Eric, Hill, Brian, Thieblemont, Catherine, Cavallo, Federica, De la Cruz, Fatima, Kuruvilla, John, Hamad, Nada, Jaeger, Ulrich, Caimi, Paolo, Gurion, Ronit, Warzocha, Krzysztof, Bakhshi, Sameer, Sancho, Juan-Manuel, Schuster, Michael, Egyed, Miklos, Offner, Fritz, Vassilakopoulos, Theodoros P., Samal, Priyanka, Ku, Matthew, Ma, Xiwen, Corona, Kelly, Chamoun, Kamal, Shah, Jatin, Shacham, Sharon, Kauffman, Michael G., and Canales, Miguel

Published
2021
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15. Penalized Likelihood Regression in Reproducing Kernel Hilbert Spaces with Randomized Covariate Data

Author

Ma, Xiwen, Dai, Bin, Klein, Ronald, Klein, Barbara E. K., Lee, Kristine E., and Wahba, Grace

Subjects
Statistics - Methodology, Statistics - Applications
Abstract

Classical penalized likelihood regression problems deal with the case that the independent variables data are known exactly. In practice, however, it is common to observe data with incomplete covariate information. We are concerned with a fundamentally important case where some of the observations do not represent the exact covariate information, but only a probability distribution. In this case, the maximum penalized likelihood method can be still applied to estimating the regression function. We first show that the maximum penalized likelihood estimate exists under a mild condition. In the computation, we propose a dimension reduction technique to minimize the penalized likelihood and derive a GACV (Generalized Approximate Cross Validation) to choose the smoothing parameter. Our methods are extended to handle more complicated incomplete data problems, such as, covariate measurement error and partially missing covariates., Comment: 46 pages Missing data is a special case of the general theory here

Published
2010

20. A population-adjusted indirect treatment comparison of efficacy and safety of aumolertinib vs osimertinib in EGFR-mutated non-small cell lung cancer

Author

King, Sarah, primary, Stergiopoulos, Stella, additional, Curtis, Melissa, additional, Dillon, Andrew, additional, Akehurst, Ron, additional, Lee, Dawn, additional, Guelfucci, Florent, additional, Ngami, Armel, additional, Bianic, Florence, additional, Li, You, additional, Ma, Xiwen, additional, Ali, Siraj, additional, Miller, Vincent, additional, and Popat, Sanjay, additional

Published
2023
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21. Supplementary Tables S1-S7 from Whole-Genome Sequencing of Asian Lung Cancers: Second-Hand Smoke Unlikely to Be Responsible for Higher Incidence of Lung Cancer among Asian Never-Smokers

Author

Krishnan, Vidhya G., primary, Ebert, Philip J., primary, Ting, Jason C., primary, Lim, Elaine, primary, Wong, Swee-Seong, primary, Teo, Audrey S.M., primary, Yue, Yong G., primary, Chua, Hui-Hoon, primary, Ma, Xiwen, primary, Loh, Gary S.L., primary, Lin, Yuhao, primary, Tan, Joanna H.J., primary, Yu, Kun, primary, Zhang, Shenli, primary, Reinhard, Christoph, primary, Tan, Daniel S.W., primary, Peters, Brock A., primary, Lincoln, Stephen E., primary, Ballinger, Dennis G., primary, Laramie, Jason M., primary, Nilsen, Geoffrey B., primary, Barber, Thomas D., primary, Tan, Patrick, primary, Hillmer, Axel M., primary, and Ng, Pauline C., primary

Published
2023
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22. Supplementary Figure Legends from Whole-Genome Sequencing of Asian Lung Cancers: Second-Hand Smoke Unlikely to Be Responsible for Higher Incidence of Lung Cancer among Asian Never-Smokers

Author

Krishnan, Vidhya G., primary, Ebert, Philip J., primary, Ting, Jason C., primary, Lim, Elaine, primary, Wong, Swee-Seong, primary, Teo, Audrey S.M., primary, Yue, Yong G., primary, Chua, Hui-Hoon, primary, Ma, Xiwen, primary, Loh, Gary S.L., primary, Lin, Yuhao, primary, Tan, Joanna H.J., primary, Yu, Kun, primary, Zhang, Shenli, primary, Reinhard, Christoph, primary, Tan, Daniel S.W., primary, Peters, Brock A., primary, Lincoln, Stephen E., primary, Ballinger, Dennis G., primary, Laramie, Jason M., primary, Nilsen, Geoffrey B., primary, Barber, Thomas D., primary, Tan, Patrick, primary, Hillmer, Axel M., primary, and Ng, Pauline C., primary

Published
2023
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23. Supplementary Figure S2 from Whole-Genome Sequencing of Asian Lung Cancers: Second-Hand Smoke Unlikely to Be Responsible for Higher Incidence of Lung Cancer among Asian Never-Smokers

Author

Krishnan, Vidhya G., primary, Ebert, Philip J., primary, Ting, Jason C., primary, Lim, Elaine, primary, Wong, Swee-Seong, primary, Teo, Audrey S.M., primary, Yue, Yong G., primary, Chua, Hui-Hoon, primary, Ma, Xiwen, primary, Loh, Gary S.L., primary, Lin, Yuhao, primary, Tan, Joanna H.J., primary, Yu, Kun, primary, Zhang, Shenli, primary, Reinhard, Christoph, primary, Tan, Daniel S.W., primary, Peters, Brock A., primary, Lincoln, Stephen E., primary, Ballinger, Dennis G., primary, Laramie, Jason M., primary, Nilsen, Geoffrey B., primary, Barber, Thomas D., primary, Tan, Patrick, primary, Hillmer, Axel M., primary, and Ng, Pauline C., primary

Published
2023
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24. Data from Whole-Genome Sequencing of Asian Lung Cancers: Second-Hand Smoke Unlikely to Be Responsible for Higher Incidence of Lung Cancer among Asian Never-Smokers

Author

Krishnan, Vidhya G., primary, Ebert, Philip J., primary, Ting, Jason C., primary, Lim, Elaine, primary, Wong, Swee-Seong, primary, Teo, Audrey S.M., primary, Yue, Yong G., primary, Chua, Hui-Hoon, primary, Ma, Xiwen, primary, Loh, Gary S.L., primary, Lin, Yuhao, primary, Tan, Joanna H.J., primary, Yu, Kun, primary, Zhang, Shenli, primary, Reinhard, Christoph, primary, Tan, Daniel S.W., primary, Peters, Brock A., primary, Lincoln, Stephen E., primary, Ballinger, Dennis G., primary, Laramie, Jason M., primary, Nilsen, Geoffrey B., primary, Barber, Thomas D., primary, Tan, Patrick, primary, Hillmer, Axel M., primary, and Ng, Pauline C., primary

Published
2023
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26. LSR-YOLO: A High-Precision, Lightweight Model for Sheep Face Recognition on the Mobile End

Author

Ma, Xiwen Zhang, Chuanzhong Xuan, Jing Xue, Boyuan Chen, and Yanhua

Subjects
sheep identity recognition, deep learning, YOLOv5, lightweight improvement, mobile terminal recognition
Abstract

The accurate identification of sheep is crucial for breeding, behavioral research, food quality tracking, and disease prevention on modern farms. As a result of the time-consuming, expensive, and unreliable problems of traditional sheep-identification methods, relevant studies have built sheep face recognition models to recognize sheep through facial images. However, the existing sheep face recognition models face problems such as high computational costs, large model sizes, and weak practicality. In response to the above issues, this study proposes a lightweight sheep face recognition model named LSR-YOLO. Specifically, the ShuffleNetv2 module and Ghost module were used to replace the feature extraction module in the backbone and neck of YOLOv5s to reduce floating-point operations per second (FLOPs) and parameters. In addition, the coordinated attention (CA) module was introduced into the backbone to suppress non-critical information and improve the feature extraction ability of the recognition model. We collected facial images of 63 small-tailed Han sheep to construct a sheep face dataset and further evaluate the proposed method. Compared to YOLOv5s, the FLOPs and parameters of LSR-YOLO decreased by 25.5% and 33.4%, respectively. LSR-YOLO achieved the best performance on the sheep face dataset, and the mAP@0.5 reached 97.8% when the model size was only 9.5 MB. The experimental results show that LSR-YOLO has significant advantages in recognition accuracy and model size. Finally, we integrated LSR-YOLO into mobile devices and further developed a recognition system to achieve real-time recognition. The results show that LSR-YOLO is an effective method for identifying sheep. The method has high recognition accuracy and fast recognition speed, which gives it a high application value in mobile recognition and welfare breeding.

Published
2023
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27. Multiagent Multiobjective Decision Making and Game for Saving Public Resources

Author

Ma, Xiwen, Zhang, Yibo, Xie, Wei, Yang, Jingsong, and Zhang, Weidong

Abstract

Uncertain environments and inefficient decision analysis restrict the efficient utilization of depletable public resources by multiagents, especially for the scenario involved with multiobjective game dilemmas and weak scalability of decision making. To address the above conundrums, this article proposes a multilayer games framework that integrates cognition, decision making, and countermeasures (CDCs). Through the transformation of agent preference to alliance communication structure, a cooperation-competition topology network (CCTN) model is constructed, which improves the convergence and solution efficiency of the game model. In view of the Gaussian kernel ascending dimension mapping, a game equilibrium particle swarm optimization (GEPSO) algorithm is designed to improve the efficiency of finding equilibrium solutions and solve the nondeterministic polynomial (NP) problem of multiobjective games. To validate the effectiveness and performance of the proposed methodology, a case study of collaborative detection of multivehicle is conducted using the proposed framework and model.

Published
2024
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30. Comparison of the Effectiveness and Safety of the Oral Selective Inhibitor of Nuclear Export, Selinexor, in Diffuse Large B Cell Lymphoma Subtypes.

Author

UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Service de gastro-entérologie, UCL - (SLuc) Unité d'oncologie médicale, Casasnovas, Rene-Olivier, Follows, George, Zijlstra, Josee M, Vermaat, Joost S P, Kalakonda, Nagesh, Choquet, Sylvain, Neste, Eric Van Den, Hill, Brian, Thieblemont, Catherine, Cavallo, Federica, la Cruz, Fatima De, Kuruvilla, John, Hamad, Nada, Jaeger, Ulrich, Caimi, Paolo F, Gurion, Ronit, Warzocha, Krzysztof, Bakhshi, Sameer, Sancho, Juan-Manuel, Schuster, Michael, Egyed, Miklos, Offner, Fritz, Vassilakopoulos, Theodoros P, Samal, Priyanka, Ku, Matthew, Ma, Xiwen, Chamoun, Kamal, Shah, Jatin, Canales, Miguel, Maerevoet, Marie, Shacham, Sharon, Kauffman, Michael G, Goy, Andre, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Service de gastro-entérologie, UCL - (SLuc) Unité d'oncologie médicale, Casasnovas, Rene-Olivier, Follows, George, Zijlstra, Josee M, Vermaat, Joost S P, Kalakonda, Nagesh, Choquet, Sylvain, Neste, Eric Van Den, Hill, Brian, Thieblemont, Catherine, Cavallo, Federica, la Cruz, Fatima De, Kuruvilla, John, Hamad, Nada, Jaeger, Ulrich, Caimi, Paolo F, Gurion, Ronit, Warzocha, Krzysztof, Bakhshi, Sameer, Sancho, Juan-Manuel, Schuster, Michael, Egyed, Miklos, Offner, Fritz, Vassilakopoulos, Theodoros P, Samal, Priyanka, Ku, Matthew, Ma, Xiwen, Chamoun, Kamal, Shah, Jatin, Canales, Miguel, Maerevoet, Marie, Shacham, Sharon, Kauffman, Michael G, and Goy, Andre

Abstract

The SADAL study evaluated oral selinexor in patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL) after at least 2 prior lines of systemic therapy. In this post-hoc analysis, we analyzed the outcomes of the SADAL study by DLBCL subtype to determine the effects of DLBCL subtypes on efficacy and tolerability of selinexor. Data from 134 patients in SADAL were analyzed by DLBCL subtypes for overall response rate (ORR), overall survival (OS), duration of treatment response, progression-free survival, and adverse events rate. ORR in the entire cohort was 29.1%, and similar in patients with germinal center (GCB) versus non-GCB DLBCL (31.7% vs. 24.2%, P = 0.45); transformed DLBCL showed a trend towards higher ORR than de novo DLBCL: 38.7% vs. 26.2% (P = 0.23). Despite similar prior treatment regimens and baseline characteristics, patients with DLBCL and normal C-MYC/BCL-2 protein expression levels had a significantly higher ORR (46.2% vs.14.8%, P = 0.012) and significantly longer OS (medians 13.7 vs. 5.1 months, hazard ratio 0.43 [95% CI, 0.23-0.77], P = 0.004) as compared with those whose DLBCL had C-MYC and BCL-2 overexpression. Among patients who had normal expression levels of either C-MYC or BCL-2 and baseline hemoglobin levels ≥ 10g/dL, ORR was 51.5% (n = 47), with median OS of 15.5 months and median PFS of 4.6 months. Similar rates of adverse events were noted in all subgroups. Overall, single agent oral selinexor showed strong responses in patients with limited treatment alternatives regardless of germinal center B-cell type or disease origin.

Published
2022

31. Effect of Prior Therapy and Disease Refractoriness on the Efficacy and Safety of Oral Selinexor in Patients with Diffuse Large B-cell Lymphoma (DLBCL): A Post-hoc Analysis of the SADAL Study.

Author

UCL - (SLuc) Centre du cancer, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, UCL - (SLuc) Service de rhumatologie, Schuster, Michael, Zijlstra, Josée, Casasnovas, Rene-Olivier, Vermaat, Joost S P, Kalakonda, Nagesh, Goy, Andre, Choquet, Sylvain, Neste, Eric Van Den, Hill, Brian, Thieblemont, Catherine, Cavallo, Federica, De la Cruz, Fatima, Kuruvilla, John, Hamad, Nada, Jaeger, Ulrich, Caimi, Paolo, Gurion, Ronit, Warzocha, Krzysztof, Bakhshi, Sameer, Sancho, Juan-Manuel, Follows, George, Egyed, Miklos, Offner, Fritz, Vassilakopoulos, Theodoros, Samal, Priyanka, Ku, Matthew, Ma, Xiwen, Corona, Kelly, Chamoun, Kamal, Shah, Jatin, Shacham, Sharon, Kauffman, Michael G, Canales, Miguel, Maerevoet, Marie, UCL - (SLuc) Centre du cancer, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, UCL - (SLuc) Service de rhumatologie, Schuster, Michael, Zijlstra, Josée, Casasnovas, Rene-Olivier, Vermaat, Joost S P, Kalakonda, Nagesh, Goy, Andre, Choquet, Sylvain, Neste, Eric Van Den, Hill, Brian, Thieblemont, Catherine, Cavallo, Federica, De la Cruz, Fatima, Kuruvilla, John, Hamad, Nada, Jaeger, Ulrich, Caimi, Paolo, Gurion, Ronit, Warzocha, Krzysztof, Bakhshi, Sameer, Sancho, Juan-Manuel, Follows, George, Egyed, Miklos, Offner, Fritz, Vassilakopoulos, Theodoros, Samal, Priyanka, Ku, Matthew, Ma, Xiwen, Corona, Kelly, Chamoun, Kamal, Shah, Jatin, Shacham, Sharon, Kauffman, Michael G, Canales, Miguel, and Maerevoet, Marie

Abstract

Despite a number of treatment options, patients with diffuse large B-cell lymphoma (DLBCL) whose disease has become refractory to treatment have a poor prognosis. Selinexor is a novel, oral drug that is approved to treat patients with relapsed/refractory DLBCL. In this post hoc analysis of the SADAL study, a multinational, open-label study, we evaluated subpopulations to determine if response to single agent selinexor is impacted by number of lines of prior treatment, autologous stem cell transplant (ASCT), response to first and most recent therapies, and time to progressive disease. Patients (n = 134) with DLBCL after 2-5 prior therapies were enrolled in SADAL and received 60mg selinexor twice weekly. The median overall survival was 9.0 months and median progression free survival was 2.6 months. Patients who had the best overall response rate (ORR) and disease control rate were those who had prior ASCT (42.5% and 50.0%) or responded to last line of therapy (35.9% and 43.5%). Patients with primary refractory DLBCL also showed responses (ORR 21.8%). Adverse events between subgroups were similar to the overall study population, the most common being thrombocytopenia (29.1%), fatigue (7.5%), and nausea (6.0%). Regardless of prior therapy and disease refractory status, selinexor treatment demonstrated results consistent with its novel mechanism of action and lack of cross-resistance. Thus, single agent oral selinexor can induce deep, durable, and tolerable responses in patients with DLBCL who have recurrent disease after several chemoimmunotherapy combination regimens.

Published
2022

33. Multi-autonomous underwater vehicles collaboratively search for intelligent targets in an unknown environment in the presence of interception

Author

Chen Yanli, Ma Xiwen, Jun Liu, Sha Yongbai, and Guiqiang Bai

Subjects
0209 industrial biotechnology, 020901 industrial engineering & automation, Computer science, Mechanical Engineering, Real-time computing, 0202 electrical engineering, electronic engineering, information engineering, 020201 artificial intelligence & image processing, 02 engineering and technology, Interception, Underwater
Abstract

We present a bionic neural wave network that uses multiple autonomous underwater vehicles to search and acquire intelligent targets in an unknown underwater environment. The neuron pheromone content is arranged according to neural wave diffusion and layer-by-layer energy attenuation, when underwater mesh space based on neural wave diffusion theory was established that the neuron nodes in the neural network structure correspond to obstacles, autonomous underwater vehicles, and targets in the environment. In order to solve the problems of over-allocation and under-allocation of the multi-autonomous underwater vehicles system during the cooperative capture of targets, a redistribution mechanism based on the improved self-organizing map algorithm is implemented and directed to rationalize task distribution. Two different taboo search methods are employed to update the autonomous underwater vehicle path in real time, and the polynomial coefficient solution method is used to fit partial path data. So that the autonomous underwater vehicle trajectory can be obtained and an interceptor position coordinate can be predicted. An auxiliary autonomous underwater vehicle is aimed to replace the intercepted autonomous underwater vehicle and the matching capture points are tracked to ensure the completion of the task so that the full range of hunting targets is identified. In order to simulate an unknown complex underwater environment, obstacles are randomly arranged around the target, the location information of the obstacle, and the target is unknown and unpredictable. Four simulation experiments were performed to verify the accuracy and efficiency of the algorithm under unknown environment. The results show that this algorithm can improve the path update average efficiency by 66% compared with other algorithms. Obviously, this algorithm is reasonable and effective.

Published
2020

34. Multi-AUV Collaborative Operation Based on Time-Varying Navigation Map and Dynamic Grid Model

Author

Chen Yanli, Jun Liu, Ma Xiwen, and Guiqiang Bai

Subjects
multiple AUV, dynamic navigation maps, General Computer Science, Computer science, Node (networking), media_common.quotation_subject, General Engineering, Boundary (topology), Recursion (computer science), Construct (python library), Function (mathematics), Grid, Adaptability, Computer Science::Robotics, Boundary function, Path length, Control theory, space decomposition, General Materials Science, lcsh:Electrical engineering. Electronics. Nuclear engineering, lcsh:TK1-9971, dynamic grid model, media_common
Abstract

In a dynamic and complex environment, to improve the cooperative operation efficiency of multiple AUV groups, a bionic neural wave network (BNWN) algorithm, and a velocity vector synthesis (VVS) algorithm are proposed. A strategy of space decomposition and node space recursion is adopted to provide dynamic navigation maps for AUV monomers and to modularize the tasks. A closed boundary function is introduced to construct a dynamic grid model to autonomously avoid obstacles with multiple moving forms. The results of three sets of simulation experiments show that the number of changes in direction, the total path length, and the collision rate of AUV individuals are greatly reduced. These results prove that the proposed algorithm has high autonomy and strong adaptability.

Published
2020

35. Comparison of the Effectiveness and Safety of the Oral Selective Inhibitor of Nuclear Export, Selinexor, in Diffuse Large B Cell Lymphoma Subtypes

Author

Casasnovas, Rene-Olivier Follows, George Zijlstra, Josee M. and Vermaat, Joost S. P. Kalakonda, Nagesh Choquet, Sylvain Van den Neste, Eric Hill, Brian Thieblemont, Catherine Cavallo, Federica De la Cruz, Fatima Kuruvilla, John Hamad, Nada and Jaeger, Ulrich Caimi, Paolo F. Gurion, Ronit Warzocha, Krzysztof Bakhshi, Sameer Sancho, Juan-Manuel Schuster, Michael Egyed, Miklos Offner, Fritz Vassilakopoulos, Theodoros P. Samal, Priyanka Ku, Matthew Ma, Xiwen and Chamoun, Kamal Shah, Jatin Canales, Miguel Maerevoet, Marie and Shacham, Sharon Kauffman, Michael G. Goy, Andre

Subjects
immune system diseases, hemic and lymphatic diseases
Abstract

The phase 2b, open-label, multicenter SADAL study evaluated single agent oral selinexor, a selective inhibitor of nuclear export (SINE) compound, in patients with diffuse large B cell lymphoma (DLBCL) after >= 2 lines of systemic therapy. Similar activity was observed in GCB- and non-GCB DLBCL with a trend to higher response rates in DLBCL transformed from follicular lymphoma. Lower response rates were observed in double expressor DLBCL; higher response rates were observed in patients with baseline hemoglobin >= 10 g/dL and normal levels of C-MYC or BCL-2 expression (51%). Overall, strong single agent activity with selinexor were observed in patients with relapsed/refractory DLBCL. Background: The SADAL study evaluated oral selinexor in patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL) after at least 2 prior lines of systemic therapy. In this post-hoc analysis, we analyzed the outcomes of the SADAL study by DLBCL subtype to determine the effects of DLBCL subtypes on efficacy and tolerability of selinexor. Patients and Methods: Data from 134 patients in SADAL were analyzed by DLBCL subtypes for overall response rate (ORR), overall survival (OS), duration of treatment response, progression-free survival, and adverse events rate. Results: ORR in the entire cohort was 29.1%, and similar in patients with germinal center (GCB) versus non-GCB DLBCL (31.7% vs. 24.2%, P = 0.45); transformed DLBCL showed a trend towards higher ORR than de novo DLBCL: 38.7% vs. 26.2% (P = 0.23). Despite similar prior treatment regimens and baseline characteristics, patients with DLBCL and normal C-MYC/BCL-2 protein expression levels had a significantly higher ORR (46.2% vs.14.8%, P = 0.012) and significantly longer OS (medians 13.7 vs. 5.1 months, hazard ratio 0.43 [95% CI, 0.23-0.77], P = 0.004) as compared with those whose DLBCL had C-MYC and BCL-2 overexpression. Among patients who had normal expression levels of either C-MYC or BCL-2 and baseline hemoglobin levels >= 10g/dL, ORR was 51.5% (n = 47), with median OS of 15.5 months and median PFS of 4.6 months. Similar rates of adverse events were noted in all subgroups. Conclusions: Overall, single agent oral selinexor showed strong responses in patients with limited treatment alternatives regardless of germinal center B-cell type or disease origin. (C) 2021 Elsevier Inc. All rights reserved.

Published
2022

36. A phase 1 clinical trial of oral eltanexor in patients with relapsed or refractory multiple myeloma

Author

Cornell, Robert Frank, primary, Baz, Rachid, additional, Richter, Joshua R., additional, Rossi, Adriana, additional, Vogl, Dan T., additional, Chen, Christine, additional, Shustik, Chaim, additional, Alvarez, Mariano J., additional, Shen, Yao, additional, Unger, T. J., additional, Ben‐Shahar, Osnat, additional, Wang, Hongwei, additional, Baloglu, Erkan, additional, Senapedis, William, additional, Ma, Xiwen, additional, Landesman, Yosef, additional, Bai, Xiang, additional, Bader, Justin, additional, Xu, Hongmei, additional, Marshall, Tracey, additional, Chang, Hua, additional, Walker, Christopher J., additional, Shah, Jatin, additional, Shacham, Sharon, additional, Kauffman, Michael G., additional, and Hofmeister, Craig C., additional

Published
2021
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37. A Phase 2/3, Multicenter Randomized Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) with or without Selinexor in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (RR DLBCL)

Author

Lee, Seung Tae, primary, Pinto, Antonio, additional, Yimer, Habte, additional, Stevens, Don, additional, Knopinska Posluszny, Wanda, additional, Shum, Merrill Kingman, additional, Manda, Sudhir, additional, Leiba, Merav, additional, Canales, Miguel, additional, Kaźmierczak, Maciej, additional, Jurczak, Wojciech, additional, Sureda, Anna, additional, Ma, Xiwen, additional, Li, Kai, additional, Ingalls, Kimberly, additional, Arriola, Tara, additional, Arazy, Melina, additional, Shah, Jatin J., additional, Shacham, Sharon, additional, Kauffman, Michael G., additional, and Nowakowski, Grzegorz S., additional

Published
2021
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38. Health-related quality of life and pain with selinexor in patients with advanced dedifferentiated liposarcoma

Author

Gounder, Mrinal, primary, Abdul Razak, Albiruni R, additional, Gilligan, Adrienne M, additional, Leong, Hoyee, additional, Ma, Xiwen, additional, Somaiah, Neeta, additional, Chawla, Sant P, additional, Martin-Broto, Javier, additional, Grignani, Giovanni, additional, Schuetze, Scott M, additional, Vincenzi, Bruno, additional, Wagner, Andrew J, additional, Chmielowski, Bartosz, additional, Jones, Robin L, additional, Shah, Jatin, additional, Shacham, Sharon, additional, Kauffman, Michael, additional, Riedel, Richard F, additional, and Attia, Steven, additional

Published
2021
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39. Peripheral neuropathy symptoms, pain, and functioning in previously treated multiple myeloma patients treated with selinexor, bortezomib, and dexamethasone

Author

Sanchez, Larysa, primary, Leleu, Xavier, additional, Beaumont, Jennifer L., additional, Yu, Hailin, additional, Hudgens, Stacie, additional, Simonova, Maryana, additional, Auner, Holger W., additional, Quach, Hang, additional, Delimpasi, Sosana, additional, Špička, Ivan, additional, Pour, Ludĕk, additional, Kriachok, Iryna, additional, Dimopoulos, Meletios A., additional, Usenko, Ganna, additional, Hájek, Roman, additional, Benjamin, Reuben, additional, Sinha, Dinesh Kumar, additional, Venner, Christopher, additional, Illmer, Thomas, additional, Garg, Mamta Krishnan, additional, Stevens, Don Ambrose, additional, Jagannath, Sundar, additional, Levy, Moshe, additional, Anderson, Larry D., additional, Bahlis, Nizar Jacques, additional, Facon, Thierry, additional, Cavo, Michele, additional, Chai, Yi, additional, Ma, Xiwen, additional, Tang, Shijie, additional, Leong, Hoyee, additional, Shah, Jatin, additional, Shacham, Sharon, additional, Kauffman, Michael, additional, Richardson, Paul, additional, and Grosicki, Sebastian, additional

Published
2021
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40. Survival among patients with relapsed/refractory diffuse large B cell lymphoma treated with single-agent selinexor in the SADAL study

Author

Maerevoet, Marie Zijlstra, Josee M. Follows, George and Casasnovas, Rene-Olivier Vermaat, J. S. P. Kalakonda, Nagesh and Goy, Andre Choquet, Sylvain Van den Neste, Eric Hill, Brian and Thieblemont, Catherine Cavallo, Federica De la Cruz, Fatima and Kuruvilla, John Hamad, Nada Jaeger, Ulrich Caimi, Paolo and Gurion, Ronit Warzocha, Krzysztof Bakhshi, Sameer and Sancho, Juan-Manuel Schuster, Michael Egyed, Miklos Offner, Fritz Vassilakopoulos, Theodoros P. Samal, Priyanka Ku, Matthew Ma, Xiwen Corona, Kelly Chamoun, Kamal Shah, Jatin Shacham, Sharon Kauffman, Michael G. Canales, Miguel

Abstract

Patients with RR DLBCL who have received >= 2 lines of therapy have limited treatment options and an expected overall survival (OS) of < 6 months. The SADAL study evaluated single-agent oral selinexor in patients with RR DLBCL and demonstrated an overall response rate (ORR) of 29.1% with median duration of response (DOR) of 9.3 months. The analyses described here evaluated a number of subpopulations in order to understand how response correlates with survival outcomes in order to identify patients who could most optimally benefit from selinexor treatment. Median age was 67 years; 44.8% of patients were >= 70 years of age. The median OS was 9.0 months (95% CI 6.2, 13.7) at a median follow-up of 14.8 months. The median OS was not reached in patients with a CR or PR, while patients who did not respond have a median OS of 4.9 months (p < 0.0001). Patients < 70 years had an OS of 11.1 months compared with 7.8 months in patients >= 70 years. Among patients with or without prior ASCT, the median OS was 10.9 and 7.8 months, respectively. Among patients with disease refractory to the most recent DLBCL treatment regimen, the median OS was 7.0 months compared with 11.1 months for disease not refractory to the most recent treatment. In a patient population in which survival is expected to be < 6 months, treatment with single-agent oral selinexor was associated with a median survival of 9 months. Increased median OS observed in patients responding to selinexor was consistent across subgroups regardless of age, prior ASCT therapy, or refractory status. Randomized studies of selinexor in combination with a variety of other anti-DLBCL agents are planned.

Published
2021

41. Peripheral neuropathy symptoms, pain, and functioning in previously treated multiple myeloma patients treated with selinexor, bortezomib, and dexamethasone

Author

Sanchez, Larysa Leleu, Xavier Beaumont, Jennifer L. Yu, Hailin Hudgens, Stacie Simonova, Maryana Auner, Holger W. and Quach, Hang Delimpasi, Sosana Spicka, Ivan Pour, Ludek and Kriachok, Iryna Dimopoulos, Meletios A. Usenko, Ganna and Hajek, Roman Benjamin, Reuben Sinha, Dinesh Kumar Venner, Christopher Illmer, Thomas Garg, Mamta Krishnan Stevens, Don Ambrose Jagannath, Sundar Levy, Moshe Anderson, Jr., Larry D. Bahlis, Nizar Jacques Facon, Thierry Cavo, Michele and Chai, Yi Ma, Xiwen Tang, Shijie Leong, Hoyee Shah, Jatin and Shacham, Sharon Kauffman, Michael Richardson, Paul and Grosicki, Sebastian

Published
2021

42. Additional file 1 of Survival among patients with relapsed/refractory diffuse large B cell lymphoma treated with single-agent selinexor in the SADAL study

Author

Maerevoet, Marie, Zijlstra, Josee M., Follows, George, Casasnovas, Rene-Olivier, Vermaat, J. S. P., Kalakonda, Nagesh, Goy, Andre, Choquet, Sylvain, Van Den Neste, Eric, Hill, Brian, Thieblemont, Catherine, Cavallo, Federica, De la Cruz, Fatima, Kuruvilla, John, Hamad, Nada, Jaeger, Ulrich, Caimi, Paolo, Gurion, Ronit, Warzocha, Krzysztof, Bakhshi, Sameer, Sancho, Juan-Manuel, Schuster, Michael, Egyed, Miklos, Offner, Fritz, Vassilakopoulos, Theodoros P., Samal, Priyanka, Ku, Matthew, Ma, Xiwen, Corona, Kelly, Chamoun, Kamal, Shah, Jatin, Shacham, Sharon, Kauffman, Michael G., and Canales, Miguel

Abstract

Additional file 1. Supplemental Material.

Published
2021
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43. Survival among patients with relapsed/refractory diffuse large B cell lymphoma treated with single-agent selinexor in the SADAL study

Author

UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Service d'hématologie, Maerevoet, Marie, Zijlstra, Josee M., Follows, George, Casasnovas, Rene-Olivier, Vermaat, J. S. P., Kalakonda, Nagesh, Goy, Andre, Choquet, Sylvain, Van Den Neste, Eric, Hill, Brian, Thieblemont, Catherine, Cavallo, Federica, De la Cruz, Fatima, Kuruvilla, John, Hamad, Nada, Jaeger, Ulrich, Caimi, Paolo, Gurion, Ronit, Warzocha, Krzysztof, Bakhshi, Sameer, Sancho, Juan-Manuel, Schuster, Michael, Egyed, Miklos, Offner, Fritz, Vassilakopoulos, Theodoros P., Samal, Priyanka, Ku, Matthew, Ma, Xiwen, Corona, Kelly, Chamoun, Kamal, Shah, Jatin, Shacham, Sharon, Kauffman, Michael G., Canales, Miguel, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Service d'hématologie, Maerevoet, Marie, Zijlstra, Josee M., Follows, George, Casasnovas, Rene-Olivier, Vermaat, J. S. P., Kalakonda, Nagesh, Goy, Andre, Choquet, Sylvain, Van Den Neste, Eric, Hill, Brian, Thieblemont, Catherine, Cavallo, Federica, De la Cruz, Fatima, Kuruvilla, John, Hamad, Nada, Jaeger, Ulrich, Caimi, Paolo, Gurion, Ronit, Warzocha, Krzysztof, Bakhshi, Sameer, Sancho, Juan-Manuel, Schuster, Michael, Egyed, Miklos, Offner, Fritz, Vassilakopoulos, Theodoros P., Samal, Priyanka, Ku, Matthew, Ma, Xiwen, Corona, Kelly, Chamoun, Kamal, Shah, Jatin, Shacham, Sharon, Kauffman, Michael G., and Canales, Miguel

Abstract

Patients with RR DLBCL who have received ≥ 2 lines of therapy have limited treatment options and an expected overall survival (OS) of < 6 months. The SADAL study evaluated single-agent oral selinexor in patients with RR DLBCL and demonstrated an overall response rate (ORR) of 29.1% with median duration of response (DOR) of 9.3 months. The analyses described here evaluated a number of subpopulations in order to understand how response correlates with survival outcomes in order to identify patients who could most optimally benefit from selinexor treatment. Median age was 67 years; 44.8% of patients were ≥ 70 years of age. The median OS was 9.0 months (95% CI 6.2, 13.7) at a median follow-up of 14.8 months. The median OS was not reached in patients with a CR or PR, while patients who did not respond have a median OS of 4.9 months (p < 0.0001). Patients < 70 years had an OS of 11.1 months compared with 7.8 months in patients ≥ 70 years. Among patients with or without prior ASCT, the median OS was 10.9 and 7.8 months, respectively. Among patients with disease refractory to the most recent DLBCL treatment regimen, the median OS was 7.0 months compared with 11.1 months for disease not refractory to the most recent treatment. In a patient population in which survival is expected to be < 6 months, treatment with single-agent oral selinexor was associated with a median survival of 9 months. Increased median OS observed in patients responding to selinexor was consistent across subgroups regardless of age, prior ASCT therapy, or refractory status. Randomized studies of selinexor in combination with a variety of other anti-DLBCL agents are planned. This trial was registered at ClinicalTrials.gov (NCT02227251) on August 28, 2014.

Published
2021

44. Comparison of the Effectiveness and Safety of the Oral Selective Inhibitor of Nuclear Export, Selinexor, in Diffuse Large B Cell Lymphoma Subtypes

Author

Casasnovas, René Olivier, Follows, George, Zijlstra, Josée J.M., Vermaat, Joost J.S.P., Kalakonda, Nagesh, Choquet, Sylvain, Neste, Eric Van Den, Hill, Brian, Thieblemont, Catherine, Cavallo, Federica, La Cruz, Fátima De, Kuruvilla, John, Hamad, Nada, Jaeger, Ulrich, Caimi, Paolo, Gurion, Ronit, Warzocha, Krzysztof, Bakhshi, Sameer, Sancho, Juan Manuel, Schuster, Michael, Egyed, Miklos, Offner, Fritz, Vassilakopoulos, Theodoros, Samal, Priyanka, Ku, Matthew, Ma, Xiwen, Chamoun, Kamal, Shah, Jatin, Canales, Miguel, Maerevoet, Marie, Shacham, Sharon, Kauffman, Michael, Goy, Andre, Casasnovas, René Olivier, Follows, George, Zijlstra, Josée J.M., Vermaat, Joost J.S.P., Kalakonda, Nagesh, Choquet, Sylvain, Neste, Eric Van Den, Hill, Brian, Thieblemont, Catherine, Cavallo, Federica, La Cruz, Fátima De, Kuruvilla, John, Hamad, Nada, Jaeger, Ulrich, Caimi, Paolo, Gurion, Ronit, Warzocha, Krzysztof, Bakhshi, Sameer, Sancho, Juan Manuel, Schuster, Michael, Egyed, Miklos, Offner, Fritz, Vassilakopoulos, Theodoros, Samal, Priyanka, Ku, Matthew, Ma, Xiwen, Chamoun, Kamal, Shah, Jatin, Canales, Miguel, Maerevoet, Marie, Shacham, Sharon, Kauffman, Michael, and Goy, Andre

Abstract

Background: The SADAL study evaluated oral selinexor in patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL) after at least 2 prior lines of systemic therapy. In this post-hoc analysis, we analyzed the outcomes of the SADAL study by DLBCL subtype to determine the effects of DLBCL subtypes on efficacy and tolerability of selinexor. Patients and Methods: Data from 134 patients in SADAL were analyzed by DLBCL subtypes for overall response rate (ORR), overall survival (OS), duration of treatment response, progression-free survival, and adverse events rate. Results: ORR in the entire cohort was 29.1%, and similar in patients with germinal center (GCB) versus non-GCB DLBCL (31.7% vs. 24.2%, P = 0.45); transformed DLBCL showed a trend towards higher ORR than de novo DLBCL: 38.7% vs. 26.2% (P = 0.23). Despite similar prior treatment regimens and baseline characteristics, patients with DLBCL and normal C-MYC/BCL-2 protein expression levels had a significantly higher ORR (46.2% vs.14.8%, P = 0.012) and significantly longer OS (medians 13.7 vs. 5.1 months, hazard ratio 0.43 [95% CI, 0.23-0.77], P = 0.004) as compared with those whose DLBCL had C-MYC and BCL-2 overexpression. Among patients who had normal expression levels of either C-MYC or BCL-2 and baseline hemoglobin levels ≥ 10g/dL, ORR was 51.5% (n = 47), with median OS of 15.5 months and median PFS of 4.6 months. Similar rates of adverse events were noted in all subgroups. Conclusions: Overall, single agent oral selinexor showed strong responses in patients with limited treatment alternatives regardless of germinal center B-cell type or disease origin., SCOPUS: ar.j, DecretOANoAutActif, info:eu-repo/semantics/published

Published
2021

45. Health-related quality of life and pain with selinexor in patients with advanced dedifferentiated liposarcoma

Author

Karyopharm Therapeutics, Daiichi-Sankyo, Amgen, Bayer, National Cancer Institute (US), National Institutes of Health (US), Merck & Co, AstraZeneca, Eli Lilly and Company, Roche, GlaxoSmithKline, Janssen Biotech, Gounder, Mrinal, Abdul Razak, Albiruni R., Gilligan, Adrienne M., Leong, Hoyee, Ma, Xiwen, Somaiah, Neeta, Chawla, Sant P., Martín-Broto, Javier, Grignani, Giovanni, Schuetze, Scott M., Vincenzi, Bruno, Wagner, Andrew J., Chmielowski, Bartosz, Jones, Robin L., Shah, Jatin, Shacham, Sharon, Kauffman, Michael, Riedel, Richard F., Attia, Steven, Karyopharm Therapeutics, Daiichi-Sankyo, Amgen, Bayer, National Cancer Institute (US), National Institutes of Health (US), Merck & Co, AstraZeneca, Eli Lilly and Company, Roche, GlaxoSmithKline, Janssen Biotech, Gounder, Mrinal, Abdul Razak, Albiruni R., Gilligan, Adrienne M., Leong, Hoyee, Ma, Xiwen, Somaiah, Neeta, Chawla, Sant P., Martín-Broto, Javier, Grignani, Giovanni, Schuetze, Scott M., Vincenzi, Bruno, Wagner, Andrew J., Chmielowski, Bartosz, Jones, Robin L., Shah, Jatin, Shacham, Sharon, Kauffman, Michael, Riedel, Richard F., and Attia, Steven

Abstract

[Objective] Compare health-related quality of life (HRQoL) of selinexor versus placebo in patients with dedifferentiated liposarcoma., [Materials & methods] HRQoL was assessed at baseline and day 1 of each cycle using the European Organization for Research and Treatment of Cancer 30-item core quality of life questionnaire. Results were reported from baseline to day 169 (where exposure to treatment was maximized while maintaining adequate sample size)., [Results] Pain scores worsened for placebo versus selinexor across all postbaseline visits, although differences in HRQoL at some visits were not significant. Other domains did not exhibit significant differences between arms; however, scores in both arms deteriorated over time., [Conclusion] Patients treated with selinexor reported lower rates and slower worsening of pain compared with patients who received placebo.

Published
2021

46. Peripheral Neuropathy Symptoms, Pain and Functioning in Relapsed or Refractory Multiple Myeloma Patients Treated with Selinexor, Bortezomib, and Dexamethasone

Author

Sanchez, Larysa, Leleu, Xavier, Beaumont, Jennifer, Yu, Hailin, Hudgens, Stacie, Auner, Holger W, Quach, Hang, Delimpasi, Sosana, Spicka, Ivan, Pour, Luděk, Dimopoulos, Meletios A, Pylypenko, Halyna, Doronin, Vadim A, Usenko, Ganna, Hajek, Roman, Benjamin, Reuben, Venner, Christopher P., Garg, Mamta, Stevens, Don A., Jagannath, Sundar, Moreau, Philippe, Levy, Moshe, Bahlis, Nizar J., Facon, Thierry, Chai, Yi, Ma, Xiwen, Tang, Shijie, Leong, Hoyee, Shah, Jatin J., Shacham, Sharon, Kauffman, Michael G, Richardson, Paul G., and Grosicki, Sebastian

Published
2020
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48. Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial.

Author

UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, UCL - (SLuc) Service d'hématologie, Kalakonda, Nagesh, Maerevoet, Marie, Cavallo, Federica, Follows, George, Goy, Andre, Vermaat, Joost S P, Casasnovas, Olivier, Hamad, Nada, Zijlstra, Josée M, Bakhshi, Sameer, Bouabdallah, Reda, Choquet, Sylvain, Gurion, Ronit, Hill, Brian, Jaeger, Ulrich, Sancho, Juan Manuel, Schuster, Michael, Thieblemont, Catherine, De la Cruz, Fátima, Egyed, Miklos, Mishra, Sourav, Offner, Fritz, Vassilakopoulos, Theodoros P, Warzocha, Krzysztof, McCarthy, Daniel, Ma, Xiwen, Corona, Kelly, Saint-Martin, Jean-Richard, Chang, Hua, Landesman, Yosef, Joshi, Anita, Wang, Hongwei, Shah, Jatin, Shacham, Sharon, Kauffman, Michael, Van Den Neste, Eric, Canales, Miguel A, UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, UCL - (SLuc) Service d'hématologie, Kalakonda, Nagesh, Maerevoet, Marie, Cavallo, Federica, Follows, George, Goy, Andre, Vermaat, Joost S P, Casasnovas, Olivier, Hamad, Nada, Zijlstra, Josée M, Bakhshi, Sameer, Bouabdallah, Reda, Choquet, Sylvain, Gurion, Ronit, Hill, Brian, Jaeger, Ulrich, Sancho, Juan Manuel, Schuster, Michael, Thieblemont, Catherine, De la Cruz, Fátima, Egyed, Miklos, Mishra, Sourav, Offner, Fritz, Vassilakopoulos, Theodoros P, Warzocha, Krzysztof, McCarthy, Daniel, Ma, Xiwen, Corona, Kelly, Saint-Martin, Jean-Richard, Chang, Hua, Landesman, Yosef, Joshi, Anita, Wang, Hongwei, Shah, Jatin, Shacham, Sharon, Kauffman, Michael, Van Den Neste, Eric, and Canales, Miguel A

Abstract

BACKGROUND: Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer with a median overall survival of less than 6 months. We aimed to assess the response to single-agent selinexor, an oral selective inhibitor of nuclear export, in patients with relapsed or refractory DLBCL who had no therapeutic options of potential clinical benefit. METHODS: SADAL was a multicentre, multinational, open-label, phase 2b study done in 59 sites in 19 countries. Patients aged 18 years or older with pathologically confirmed diffuse large B-cell lymphoma, an Eastern Cooperative Oncology Group performance status of 2 or less, who had received two to five lines of previous therapies, and progressed after or were not candidates for autologous stem-cell transplantation were enrolled. Germinal centre B-cell or non-germinal centre B-cell tumour subtype and double or triple expressor status were determined by immunohistochemistry and double or triple hit status was determined by cytogenetics. Patients received 60 mg selinexor orally on days 1 and 3 weekly until disease progression or unacceptable toxicity. The study was initially designed to evaluate both 60 mg and 100 mg twice-weekly doses of selinexor; however, the 100 mg dose was discontinued in the protocol (version 7.0) on March 29, 2017, when an improved therapeutic window was observed at 60 mg. Primary outcome was overall response rate. The primary outcome and safety were assessed in all patients who received 60 mg selinexor under protocol version 6.0, or enrolled under protocol versions 7.0 or higher and received at least one dose of selinexor. This trial is registered at ClinicalTrials.gov, NCT02227251 (active but not enrolling). FINDINGS: Between Oct 21, 2015, and Nov 2, 2019, 267 patients were randomly assigned, with 175 allocated to the 60 mg group and 92 to the discontinued 100 mg group. 48 patients assigned to the 60 mg group were excluded due to enrolment before version 6.0 of the protocol; the remaini

Published
2020

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