Multiple Myeloma Treatment in Real-world Clinical Practice : Results of a Prospective, Multinational, Noninterventional Study

Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: M.M. has received personal fees from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Sanofi, Novartis, and Takeda and grants from Janssen and Sanofi during the conduct of the study. E.T. has received grants from Janssen and personal fees from Janssen and Takeda during the conduct of the study, and grants from Amgen, Celgene/Genesis, personal fees from Amgen, Celgene/Genesis, Bristol-Myers Squibb, Novartis, and Glaxo-Smith Kline outside the submitted work. M.V.M. has received personal fees from Janssen, Celgene, Amgen, and Takeda outside the submitted work. M.C. reports honoraria from Janssen, outside the submitted work. M. B. reports grants from Janssen Cilag during the conduct of the study. M.D. has received honoraria for participation on advisory boards for Janssen, Celgene, Takeda, Amgen, and Novartis. H.S. has received honoraria from Janssen-Cilag, Celgene, Amgen, Bristol-Myers Squibb, Novartis, and Takeda outside the submitted work. V.P. reports personal fees from Janssen during the conduct of the study and grants, personal fees, and nonfinancial support from Amgen, grants and personal fees from Sanofi, and personal fees from Takeda outside the submitted work. W.W. has received personal fees and grants from Amgen, Celgene, Novartis, Roche, Takeda, Gilead, and Janssen and nonfinancial support from Roche outside the submitted work. J.S. reports grants and nonfinancial support from Janssen Pharmaceutical during the conduct of the study. V.L. reports funding from Janssen Global Services LLC during the conduct of the study and study support from Janssen-Cilag and Pharmion outside the submitted work. A.P. reports employment and shareholding of Janssen (Johnson & Johnson) during the conduct of the study. C.C. reports employment at Janssen-Cilag during the conduct of the study. C.F. reports employment at Janssen Research and Development during the conduct of the study. F.T.B. reports employment at Janssen-Cilag during the conduct of the study. The remaining authors have stated that they have no conflicts of interest. Publisher Copyright: © 2018 The AuthorsMultiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.publishersversionPeer reviewe

Miocene-to-Quaternary oblique rifting signature in the Western Ross Sea from fault patterns in the McMurdo Volcanic Group, north Victoria Land, Antarctica

Mt. Overlord and Mt. Melbourne are part of the fossil-to-active eruptive centre belt of the McMurdo Volcanic Group, located along the western shoulder of the West Antarctic Rift System in north Victoria Land (Antarctica). The formation and localisation of these volcanic centres are intimately connected to the regional fault patterns associated with Neogene transtensional stretching in the West Antarctic Rift System. This study reports about 900 structural data of faults and fault-related joints affecting the Miocene-Pliocene deposits of Mt. Overlord and the Plio-Quaternary deposits of Mt. Melbourne. Fault surfaces strike along three main directions (NW-SE, NE-SW, and N-S) with high (> 70\ub0) dip angles. The reconstructed fault geometries and kinematics document a NW-SE strike-slip fault system having dextral motion in the Mt. Overlord area, which evolves into a more complex structural architecture characterised by transtensional deformations in the Mt. Melbourne area, where volcanism is still active. The fault array can be reconciled with principal and subordinate deformation structures developed at the termination region of NW-SE intraplate strike-slip fault systems inducing oblique rifting in the West Antarctic Rift System. The structural dataset, integrated with available geochronological constraints, gives rise to a two-step (Miocene-to-Holocene) tectonic scenario in which the spatial migration of the volcanic activity towards the eastern boundary of the Transantarctic Mountains occurred during the evolution of the West Antarctic Rift System

Implementation of a Fuzzy Control System for a Parallel Hybrid Vehicle Powertrain on CompactRio

In the present paper it is discussed the design and the implementation of a fuzzy control system for efficient energy management of a parallel hybrid vehicle powertrain. A simple strategy, based on two control signals is adopted to realize the split of the driver request between the internal combustion engine and the electric motor during the acceleration phases. Similarly, during the deceleration phases a dedicated set of fuzzy rules is used to control the regenerative braking. The proposed strategy has been implemented in LabView in order to easily program a compact reconfigurable input/output hardware device produced by National Instruments. The powertrain controller has been developed to be installed on a high performance sport parallel hybrid electric prototype under construction in the Polo per La Mobilità Sostenibile Laboratories

A Radial Configurations Search Algorithm for joint PFC and DFR Optimization in Smart Grids

The power loss reduction is one of the main targets for any electrical energy distribution company. In this paper the problem of the joint optimization of both topology and network parameters in a real Smart Grid is faced. A portion of the Italian electric distribution network managed by the \textit{ACEA Distribuzione S.p.A.} located in Rome is considered. It includes about 1200 user loads, 70 km of MV lines, 6 feeders, a Thyristor Voltage Regulator and 6 distributed energy sources (5 generator sets and 1 photovoltaic plant). The power factor correction (PFC) is performed tuning the 5 generator sets and setting the state of the breakers in order to perform the distributed feeder reconfiguration (DFR). About the DFR, in this paper we introduce a simplified graph representation of the electrical network and we propose a new algorithm to find all the radial network configurations. The PFC and the DFR optimization is faced by defining and solving a suited multi-objective optimization p

Actvie power losses cibstrained optimization in Smart Grids by genetic algorithms

In this paper the problem of the minimization of active power losses in a real Smart Grid located in the area of Rome is faced by defining and solving a suited multi-objective optimization problem. It is consid- ered a portion of the ACEA Distribuzione S.p.A. network which presents backflow of active power for 20% of the annual operative time. The net- work taken into consideration includes about 100 nodes, 25 km of MV lines, three feeders and three distributed energy sources (two biogas gen- erators and one photovoltaic plant). The grid has been accurately mod- eled and simulated in the phasor domain by Matlab/Simulink, relying on the SimPowerSystems ToolBox, following a Multi-Level Hierarchical and Modular approach. It is faced the problem of finding the optimal network parameters that minimize the total active power losses in the network, without violating operative constraints on voltages and currents. To this aim it is adopted a genetic algorithm, defining a suited fitness function. Tests have been performed by feeding the simulation environment with real data concerning dissipated and generated active and reactive power values. First results are encouraging and show that the proposed opti- mization technique can be adopted as the core of a hierarchical Smart Grid control system

Comparison between time-constrained and time-unconstrained optimization for power losses minimization in Smart Grids using genetic algorithms

The power losses reduction is one of the main targets for any electrical energy distribution company. This paper studies the applicability of a control system based on a Genetic Algorithm (GA) on a portion of the actual Italian electric distribution network located in Rome and surroundings, managed by the ACEA Distribuzione S.p.A. The joint optimization of both power factor correction (PFC) and distributed feeder reconfiguration (DFR) is faced. The PFC is performed tuning the phases of the distributed generators (DGs) and the output voltage of the Thyristor Voltage Regulator (TVR). The DFR is performed by opening and closing the available breakers according to a graph based algorithm that is able to find all the possible radial configurations of the network. The joint PFC and the DFR optimization problem are faced by solving a suitable optimization problem, defining the fitness function that drives the GA. In order to have the opportunity to study a realistic future scenario, the actual network has been modified by introducing a few extra distributed generators. Aiming to validate the applicability of the proposed algorithm to an operative scenario, two different tests have been performed. The first one, referred to as time-unconstrained optimization, represents an ideal scenario where there are no constraints on time available for optimization. The second one, referred to as time-constrained optimization, represents a real scenario where the optimization must be completed within a time slot of one hour. Both tests have been performed by feeding the developed simulation tool with real data concerning dissipated and generated active and reactive power values. The comparison between results obtained in the two tests campaigns furnishes the opportunity to evaluate the effectiveness of the proposed control algorithm in real time, relying on the computational performances of an entry-level workstation. The obtained results encourage the use of derivative free methods in a real-time control scenario, showing that the performances achieved by the time-constrained optimization procedures are very close in terms of objective function values to the ones obtained by the time-unconstrained procedure

Miocene-to-Quaternary oblique rifting signature in the Western Ross Sea from fault patterns in the McMurdo Volcanic Group, north Victoria Land, Antarctica

Mt. Overlord and Mt. Melbourne are part of the fossil-to-active eruptive centre belt of the McMurdo Volcanic Group, located along the western shoulder of the West Antarctic Rift System in north Victoria Land (Antarctica). The formation and localisation of these volcanic centres are intimately connected to the regional fault patterns associated with Neogene transtensional stretching in the West Antarctic Rift System. This study reports about 900 structural data of faults and fault-related joints affecting the Miocene-Pliocene deposits of Mt. Overlord and the Plio-Quaternary deposits of Mt. Melbourne. Fault surfaces strike along three main directions (NW-SE, NE-SW, and N-S) with high (> 70°) dip angles. The reconstructed fault geometries and kinematics document a NW-SE strike-slip fault system having dextral motion in the Mt. Overlord area, which evolves into a more complex structural architecture characterised by transtensional deformations in the Mt. Melbourne area, where volcanism is still active. The fault array can be reconciled with principal and subordinate deformation structures developed at the termination region of NW-SE intraplate strike-slip fault systems inducing oblique rifting in the West Antarctic Rift System. The structural dataset, integrated with available geochronological constraints, gives rise to a two-step (Miocene-to-Holocene) tectonic scenario in which the spatial migration of the volcanic activity towards the eastern boundary of the Transantarctic Mountains occurred during the evolution of the West Antarctic Rift System

Two evolutionary computational approaches for active power losses minimization in Smart Grids

In this paper the problem of the minimization of active power losses in a real Smart Grid located in the area of Rome is faced by defining and solving a suited multi-objective optimization problem. It is considered a portion of the Italian electric distribution network managed by the ACEA Distribuzione S.p.A. which presents backflow of active power for 20% of the annual operative time. The network taken into consideration includes about 1200 user loads, 70 km of MV lines, 6 feeders, a thyristor voltage regulator (TVR) and 6 distributed energy sources (5 generator sets and 1 photovoltaic plant). The grid has been accurately modeled and simulated in the phasor domain by Matlab/Simulink, relying on the SimPowerSystems ToolBox, following a Multi-Level Hierarchical and Modular approach. It is faced the problem of finding the optimal network parameters that minimize the total active power losses in the network, without violating operative constraints on voltages and currents. To this aim, a

Optimal distribution feeders configuration for active power losses minimization by genetic algorithms

In this paper we face the problem of the joint optimization of both topology and network parameters in order to minimize the total active power losses in a real Smart Grid. It is considered a portion of the Italian electric distribution network managed by the ACEA Distribuzione S.p.A. located in Rome which presents back-flows of active power for 20% of the annual operative time. It includes about 1200 user loads, 70 km of MV lines, 6 feeders, a thyristor voltage regulator (TVR) and 6 distributed energy sources (5 generator sets and 1 photovoltaic plant). Network topology can be changed by 106 breakers. The grid has been accurately modelled and simulated in the phasor domain by Matlab/Simulink, relying on the SimPowerSystems ToolBox, following a Multi-Level Hierarchical and Modular approach. Network optimization is faced by defining and solving a suited multi-objective optimization problem, considering suited constraints on nominal operative ranges on voltages and currents, as well as

Active Power Losses Constrained Optimization in Smart Grids by Genetic Algorithms

In this paper the problem of the minimization of active power losses in a real Smart Grid located in the area of Rome is faced by defining and solving a suited multi-objective optimization problem. It is considered a portion of the ACEA Distribuzione S.p.A. network which presents backflow of active power for 20% of the annual operative time. The network taken into consideration includes about 100 nodes, 25 km of MV lines, three feeders and three distributed energy sources (two biogas generators and one photovoltaic plant). The grid has been accurately modeled and simulated in the phasor domain by Matlab/Simulink, relying on the SimPowerSystems ToolBox, following a Multi-Level Hierarchical and Modular approach. It is faced the problem of finding the optimal network parameters that minimize the total active power losses in the network, without violating operative constraints on voltages and currents. To this aim it is adopted a genetic algorithm, defining a suited fitness function. Tests have been performed by feeding the simulation environment with real data concerning dissipated and generated active and reactive power values. First results are encouraging and show that the proposed optimization technique can be adopted as the core of a hierarchical Smart Grid control system. © Springer-Verlag Berlin Heidelberg 2013