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Introduction: Bruton's tyrosine kinase (BTK) inhibition is an emerging standard of care for WM. The ASPEN trial (NCT03053440) is a randomized phase 3 study comparing zanubrutinib, a potent and selective BTK inhibitor, versus ibrutinib, a first generation BTK inhibitor, in patients with WM. Method(s): Patients with MYD88 mutation-positive (MYD88mut+) WM were randomly assigned 1:1 to receive zanubrutinib (160 mg twice daily) or ibrutinib (420 mg once daily). Patients without MYD88 mutations were assigned to a separate cohort, received zanubrutinib, and are reported separately. Randomization was stratified by CXCR4 mutational status and the number of lines of prior therapy (0 vs 1-3 vs >3). The primary end point was the proportion of patients achieving a complete response or very good partial response (CR+VGPR). Sample size was calculated to provide 81% power to detect a difference in CR+VGPR rate of 35% vs 15% in the subset of patients with relapsed or refractory WM. Primary analysis was planned to occur at ~12 months after the last patient enrolled. Result(s): In total, 201 patients were randomized from Jan 2017 to Jul 2018. The treatment groups were well balanced for important baseline factors, with the exception of more elderly patients (aged >75 years, 33.3% vs 22.2%) and more anemia (hemoglobin <=110 g/L, 65.7% vs 53.5%) in the zanubrutinib arm. At a median follow-up of 19.4 months, the rate of VGPR (no CRs were observed) was 28.4% vs 19.2% with zanubrutinib vs ibrutinib, respectively (2-sided P=0.09). Rates of atrial fibrillation, contusion, diarrhea, edema peripheral, hemorrhage, muscle spasms, pneumonia, and adverse events leading to discontinuation or death were lower with zanubrutinib. The rate of neutropenia was higher with zanubrutinib (Table), but grade >=3 infection rates were similar (17.8% vs 19.4%). Conclusion(s): ASPEN is the largest phase 3 trial of BTK inhibitors in WM and the first head-to-head comparison of BTK inhibitors in any disease. Although

Introduction: Inhibitors of Bruton's tyrosine kinase (BTK) have shown significant activity in patients with MYD88 mutation-positive (MYD-88mut+) WM. However, lower response rates and shorter progression-free survival have been reported in patients with WM who lack such mutations (N Engl J Med. 2015;372:1430). The ASPEN trial (NCT03053440) evaluated zanubrutinib, a potent and selective BTK inhibitor, in patients with MYD88WT WM. Here, we present the safety and efficacy of zanubrutinib in these patients. Method(s): At study entry, bone marrow MYD88 mutations were assessed by a central laboratory (NeoGenomics). Based on these results, patients were assigned to cohort 1 (MYD88mut+) or cohort 2 (MYD88WT or unknown mutation status). Patients received zanubrutinib 160 mg twice daily until disease progression. Result(s): In total, 28 patients were enrolled in cohort 2, of which 26 were centrally confirmed as MYD88WT. Median age of patients was 72 years; five patients were treatment-naive and 23 patients had relapsed/refractory (>=1 prior therapy) WM. Most patients had intermediate-risk (39.3%) or high-risk (42.9%) disease, as defined by the International Prognostic Scoring System for WM. At median follow-up of 17.9 months, two patients discontinued zanubrutinib due to adverse events (AEs), and six experienced disease progression; there were no cases of disease transformation. In patients with confirmed MYD88WT, the overall response rate by independent review was 80.8%, with a major response rate of 50.0%, including a very good partial response rate of 26.9%. The progression-free survival event-free rate at 12 months was 72.4%. The most frequently reported AEs were diarrhea, anemia, contusion, pyrexia, and upper respiratory tract infection. Major hemorrhage was reported in two patients, and atrial fibrillation was reported in one patient. There were no fatal AEs. Conclusion(s): Zanubrutinib showed clinically meaningful antitumor activity, including achieving major responses

Background: ZANU is a potent and selective next-generation Bruton tyrosine kinase inhibitor (BTKi) designed to have greater affinity to BTK while minimizing off-target inhibition of TEC-and EGFR-family kinases. ASPEN (NCT03053440) is a randomized, open-label, phase 3 study comparing ZANU with the first-generation BTKi IBR in pts with WM. We present data with a median follow-up of 43 months. Aim(s): To compare the efficacy and safety of ZANU vs IBR in pts with MYD88 mutant (MYD88mut) WM and ZANU in pts with wild-type MYD88 (MYD88wt) WM. Method(s): Pts with MYD88mut WM were assigned to cohort 1 and randomized 1:1 to receive ZANU 160 mg twice daily or IBR 420 mg once daily. Pts with MYD88wt were assigned to cohort 2 and received ZANU 160 mg twice daily until disease progression. Randomization was stratified by CXCR4 mutational status by Sanger sequencing and lines of prior therapy (0, 1-3, or >3). All pts gave informed consent. The primary endpoint was proportion of pts achieving very good partial response or better (VGPR + complete response [CR]). Primary analysis occurred at 19 months median follow-up, and final analysis is planned to occur ~4 years after the first pt enrolled. Result(s): A total of 201 pts (102 ZANU; 99 IBR) were enrolled in cohort 1 and 28 pts in cohort 2. Baseline characteristics in cohort 1 differed between pts treated with ZANU vs IBR in CXCR4 mutations by next-generation sequencing (32% vs 20%, or 33 of 98 vs 20 of 92 available samples, respectively) and pts aged >75 years (33% vs 22%, respectively). Median duration of treatment was 42 months (ZANU) and 41 months (IBR), with 67% and 58% remaining on treatment, respectively. The VGPR+CR rate by investigator was 36% with ZANU vs 22% with IBR (descriptive p = 0.02) in cohort 1, and 31% in cohort 2. One pt in cohort 2 obtained a CR. In pts with wild-type (65 ZANU; 72 IBR) or mutant CXCR4 (33 ZANU; 20 IBR) from cohort 1, VGPR+CR rates with ZANU vs IBR were 45% vs 28% (p = 0.04) and 21% vs 5% (p = 0.

Patients with Waldenstrom macroglobulinemia (WM) lacking activating mutations in the MYD88 gene (MYD88WT) have demonstrated relatively poor outcomes to ibrutinib monotherapy, with no major responses reported in a phase 2 pivotal study. Zanubrutinib is a novel, selective Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target activity. The ASPEN study consisted of a randomized comparison of zanubrutinib and ibrutinib efficacy and safety in patients with WM who have the MYD88 mutation, as well as a separate cohort of patients without MYD88 mutation (MYD88WT) or with unknown mutational status who received zanubrutinib. Results from the latter single-arm cohort are reported herein. Efficacy endpoints included overall, major and complete (CR) or very good partial response (VGPR) rates, progression-free survival (PFS), duration of response (DOR), and overall survival (OS). Twenty-eight patients (23 relapsed/ refractory; 5 treatment-naive) were enrolled, including 26 with centrally confirmed MYD88WT disease and 2 with unknown MYD88 mutational status. At a median follow-up of 17.9 months, 7 of 26 MYD88WT patients (27%) had achieved a VGPR and 50% a major response (partial response or better); there were no CRs. At 18 months, the estimated PFS and OS rates were 68% and 88%, respectively, while the median DOR had not been reached. Two patients discontinued zanubrutinib due to adverse events. Treatment-emergent hypertension, atrial fibrillation, and major hemorrhages were reported in 3, 1 and 2 patients (including 1 concurrent with enoxaparin therapy), respectively. Results of this substudy demonstrate that zanubrutinib monotherapy can induce high quality responses in patients with MYD88WT WM. This trial is registered on www.clinicaltrials.gov as NCT #03053440.Copyright © 2020 by The American Society of Hematology

Bruton tyrosine kinase (BTK) inhibition is an effective treatment approach for patients with Waldenstrom macroglobulinemia (WM). The phase 3 ASPEN study compared the efficacy and safety of ibrutinib, a first-generation BTK inhibitor, with zanubrutinib, a novel highly selective BTK inhibitor, in patients with WM. Patients with MYD88L265P disease were randomly assigned 1:1 to treatment with ibrutinib or zanubrutinib. The primary end point was the proportion of patients achieving a complete response (CR) or a very good partial response (VGPR) by independent review. Key secondary end points included major response rate (MRR), progression-free survival (PFS), duration of response (DOR), disease burden, and safety. A total of 201 patients were randomized, and 199 received ++1 dose of study treatment. No patient achieved a CR. Twenty-nine (28%) zanubrutinib patients and 19 (19%) ibrutinib patients achieved a VGPR, a nonstatistically significant difference (P 5 .09). MRRs were 77% and 78%, respectively. Median DOR and PFS were not reached 84% and 85% of ibrutinib and zanubrutinib patients were progression free at 18 months. Atrial fibrillation, contusion, diarrhea, peripheral edema, hemorrhage, muscle spasms, and pneumonia, as well as adverse events leading to treatment discontinuation, were less common among zanubrutinib recipients. Incidence of neutropenia was higher with zanubrutinib, although grade ++3 infection rates were similar in both arms (1.2 and 1.1 events per 100 person-months). These results demonstrate that zanubrutinib and ibrutinib are highly effective in the treatment of WM, but zanubrutinib treatment was associated with a trend toward better response quality and less toxicity, particularly cardiovascular toxicity.Copyright © 2020 American Society of Hematology. All rights reserved.

Background: Inhibitors of Bruton tyrosine kinase (BTK) have shown significant activity in patients with Waldenstrom macroglobulinemia (WM) harboring a mutation in the MYD88 gene. However, lower response rates and shorter progression-free survival have been reported in patients with WM who lack such mutations (N Engl J Med. 2015;372:1430). Zanubrutinib (BGB-3111; ZANU) is an investigational, next-generation BTK inhibitor designed to maximize BTK occupancy and minimize off-target inhibition of TEC-and EGFR-family kinases. The ASPEN trial evaluated ZANU, a potent and selective BTK inhibitor, in patients with WM. Aim(s): To evaluate the efficacy and safety of ZANU in patients who have WM with MYD88 wild-type (MYD88WT) mutation status. Method(s): In the ASPEN trial, bone marrow MYD88 mutations were assessed at study entry by a central laboratory (NeoGenomics) using a wild-type-blocking polymerase chain reaction method. This MYD88 mutation assay detects all mutations in the region encompassing amino acid Ala260-Pro278, which includes the predominant mutation in WM (MYD88L265P), with enhanced sensitivity (Int J Lab Hematol. 2016;38:133). Based on the results of the MYD88 mutation assay, patients were assigned to cohort 1 (MYD88 mutation) or cohort 2 (MYD88WT or mutation unknown). All cohort 2 patients received ZANU 160 mg twice daily until disease progression. Result(s): In total, 28 patients (n = 26 MYD88WT; n = 2 MYD88 mutation status unknown) were enrolled into cohort 2. The median age was 72 years and 42.9% were > 75 years old; 5 patients were treatment-naive (TN), and 23 patients were relapsed/refractory (R/R; >=1 prior therapy). Most patients had intermediate- (39.3%) or high-risk (42.9%) disease by International Prognostic Scoring System for WM. With a median follow- up of 17.9 months, 2 patients discontinued ZANU due to adverse events, and 6 patients experienced disease progression; there were no cases of disease transformation. In 26 confirmed MYD88WT patients, th

Background: Bruton tyrosine kinase (BTK) inhibition is an emerging standard of care for Waldenstrom macroglobulinemia (WM). Zanubrutinib (BGB-3111; ZANU) is an investigational, next-generation BTK inhibitor designed to maximize BTK occupancy and minimize off-target inhibition of TEC-and EGFR-family kinases. ASPEN is a randomized phase 3 study comparing ZANU, a potent and selective BTK inhibitor, versus ibrutinib (IBR), a first generation BTK inhibitor, in patients with WM. Aim(s): To compare the efficacy and safety of ZANU versus IBR in patients with WM and MYD88 mutation. Method(s): Patients with WM and MYD88 mutation were randomly assigned 1:1 to receive ZANU (160 mg twice daily) or IBR (420 mg once daily). Patients without MYD88 mutation were assigned to a separate cohort, received ZANU, and are reported separately. Randomization was stratified by CXCR4 mutational status and the number of lines of prior therapy (0 vs 1-3 vs >3). The primary endpoint was the proportion of patients achieving a complete response or very good partial response (CR+VGPR). Sample size was calculated to provide 81% power to detect a difference in CR+VGPR rate of 35% versus 15% in the subset of patients with relapsed or refractory (R/R) WM. Primary analysis was planned to occur at approximately 12 months after the last patient enrolled. Result(s): In total, 201 patients were randomized from January 2017 to July 2018. While the treatment groups were well balanced for important baseline factors, in the ZANU arm, there were more elderly patients (aged >75 years, 33.3% vs 22.2%) and more patients with anemia (hemoglobin <=110 g/L, 65.7% vs 53.5%). At a median follow-up of 19.4 months, the rate of CR+VGPR was 28.4% vs 19.2% with ZANU vs IBR, respectively (2-sided P = 0.09). Landmark analysis at 12 months showed a trend toward longer progression-free survival and overall survival, particularly in the R/R population. Rates of adverse events leading to dose holds, dose reductions, drug discontinu

Patients with Waldenström macroglobulinemia (WM) lacking activating mutations in the MYD88 gene (MYD88WT) have demonstrated relatively poor outcomes to ibrutinib monotherapy, with no major responses reported in a phase 2 pivotal study. Zanubrutinib is a novel, selective Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target activity. The ASPEN study consisted of a randomized comparison of zanubrutinib and ibrutinib efficacy and safety in patients with WM who have the MYD88 mutation, as well as a separate cohort of patients without MYD88 mutation (MYD88WT) or with unknown mutational status who received zanubrutinib. Results from the latter single-arm cohort are reported herein. Efficacy endpoints included overall, major and complete (CR) or very good partial response (VGPR) rates, progression-free survival (PFS), duration of response (DOR), and overall survival (OS). Twenty-eight patients (23 relapsed/refractory; 5 treatment-naïve) were enrolled, including 26 with centrally confirmed MYD88WT disease and 2 with unknown MYD88 mutational status. At a median follow-up of 17.9 months, 7 of 26 MYD88WT patients (27%) had achieved a VGPR and 50% a major response (partial response or better); there were no CRs. At 18 months, the estimated PFS and OS rates were 68% and 88%, respectively, while the median DOR had not been reached. Two patients discontinued zanubrutinib due to adverse events. Treatment-emergent hypertension, atrial fibrillation, and major hemorrhages were reported in 3, 1 and 2 patients (including 1 concurrent with enoxaparin therapy), respectively. Results of this substudy demonstrate that zanubrutinib monotherapy can induce high quality responses in patients with MYD88WT WM. This trial is registered on www.clinicaltrials.gov as NCT #03053440.

We propose an object detection method using particle filters. Our approach estimates the probability of object presence in the current image given the history of observations up to current time. To do so, object presence is modelled by a two-state Markov chain, and the problem is translated into sequential Bayesian estimation which can be solved by particle filters. The observation density, required by the particle filter is based on selected discriminative Haar-like features that were introduced by Viola and Jones (2004) for object detection in static images. We illustrate the approach on the problem of face detection. Experiments on real video sequences show the feasbility of the approach., Anglais

Video security is becoming more and more important today. CCTV (closed circuit television), after broadcast television, is currently migrating from analogue to digital. At the same time, electronics have rapidly progressed in miniaturizing components and standardization initiatives have became popular in the IT world. Due to these innovations, it is now possible to deploy easily and rapidly CCTV in site for permanent or temporary uses. Examples of challenging surveillance applications are monitoring metro stations, detection of loitering or abandoned objects, etc. This chapter describes a practical implementation of a distributed surveillance system with emphasis on video transmission issues (acquisition, visualisation) and image processing necessary for useful event detection. The requirements for these systems are to be easy to use, robust and flexible. Our goals are to obtain efficiently implemented systems that can meet these strong industrial requirements. A computer cluster based approach with network connections is the innovative solution proposed. The main advantage of this approach is its flexibility. Since mobile objects are important in videosurveillance, these systems will include image analysis tools such as segmentation and object tracking. First we present the typical requirements of such a system besides the typical robustness of the analysis (e.g. low false alarm rate and low missed detection rate). We consider issues like the facility to deploy and administer network-connected real-time multicameras, with reusable modular and generic technologies. Then we analyze how to cope with the needs to integrate a solution with state-of-the-art technologies. As an answer we then propose a global system architecture and we describe its main features to explain each underlying module. To illustrate the applicability of the proposed system architecture in real case studies, we develop some scenarios of deployment for indoors or outdoors applications.

The paper presents a particle filter for integrated detection and tracking of multiple objects in image sequences, using color as the observation feature. The color based feature has been found useful when dealing with non-rigid object deformations, partial occlusions, rapidly changing dynamics and complex backgrounds. The problem of joint detection and tracking is formulated as a hybrid valued sequential state estimation problem, incorporating a discrete variable which represents the number of existing objects. The solution is implemented in the form of a particle filter. The performance of the proposed algorithm is evaluated on various real-world video sequences with objects entering and leaving the scene., Anglais

Recent works have shown that the particle filter using color as observation feature is a powerful technique for tracking deformable objects in image sequences with complex backgrounds. This paper presents a hybrid valued sequential state estimation algorithm, and its particle filter-based solution, that extends the standard color particle filter in two ways. Firstly, track initialization is embedded in the particle filter without relying on an external target detection algorithm. Secondly, the algorithm is able to track multiple objects sharing the same color description. We evaluate the performance of the proposed filter on various real-world video sequences with appearing and disappearing targets., Anglais

When combining outputs from multiple classifiers, many combination rules are available. Although easy to implement, fixed combination rules are optimal only in restrictive conditions. We discuss and evaluate their performance when the optimality conditions are not fulfilled. Fixed combination rules are then compared with trainable combination rules on real data in the context of face-based identity verification. The face images are classified by combining the outputs of five different face verification experts. It is demonstrated that a reduction in the error rates of up to 50% over the best single expert is achieved on the XM2VTS database, using either fixed or trainable combination rules. (C) 2004 Pattern Recognition Society. Published by Elsevier Ltd. All rights reserved.

This paper details the results of a face verification competition [2] held in conjunction with the First International Conference on Biometric Authentication. The contest was held on the publically available BANCA database [1] according to a defined protocol [6]. Six different verification algorithms from 4 academic and commercial institutions submitted results. Also, a standard set of face recognition software from the internet [3] was used to provide a baseline performance measure.

In this paper we study two aspects of decision fusion for enhancing face authentication. First, sequential fusion of scores obtained on successive video frames of a user's face is used to reduce the error rate. Secondly, the opinions of several face authentication algorithms are combined so that the combined decision is more accurate than the best algorithm alone. The experiments performed on a realistic database demonstrate that the fully automatic multi-frame - multi-experts system proposed in this work allows a significant improvement over the static single-expert system.

In the year 2000 a competition was organised to collect face verification results on an identical, publicly available data set using a standard evaluation protocol. The database used was the Xm2vts database along with the Lausanne protocol [14]. Four different institutions submitted results on the database which were subsequently published in [13]. Three years later, a second contest using the same dataset and protocol was organised as part of AVBPA 2003. This time round seven seperate institutions submitted results to the competition. This paper presents the results of the competition and shows that verification results on this protocol have increased in performance by a factor of 3.

We investigate the Behavior Knowledge Space [4] and Decision Templates [7] methods of classifier fusion in the context of personal identity verification involving six intramodal experts exploiting frontal face biometrics. The results of extensive experiments on the XM2VTS database show the Behavioural Knowledge Space fusion strategy achieves consistently better results than the Decision Templates method. Most importantly, it exhibits quasi monotonic behaviour as the number of experts combined increases.