Ixazomib, daratumumab and low-dose dexamethasone in intermediate-fit patients with newly diagnosed multiple myeloma:an open-label phase 2 trial

Background: The outcome of non-transplant eligible newly diagnosed multiple myeloma (NDMM) patients is heterogeneous, partly depending on frailty level. The aim of this study was to prospectively investigate the efficacy and safety of Ixazomib-Daratumumab-low-dose dexamethasone (Ixa-Dara-dex) in NDMM intermediate-fit patients. Methods: In this phase II multicenter HOVON-143 study, IMWG Frailty index based intermediate-fit patients, were treated with 9 induction cycles of Ixa-Dara-dex, followed by maintenance with ID for a maximum of 2 years. The primary endpoint was overall response rate on induction treatment. Patients were included from October 2017 until May 2019. Trial Registration Number: NTR6297. Findings: Sixty-five patients were included. Induction therapy resulted in an overall response rate of 71%. Early mortality was 1.5%. At a median follow-up of 41.0 months, median progression-free survival (PFS) was 18.2 months and 3-year overall survival 83%. Discontinuation of therapy occurred in 77% of patients, 49% due to progression, 9% due to toxicity, 8% due to incompliance, 3% due to sudden death and 8% due to other reasons. Dose modifications of ixazomib were required frequently (37% and 53% of patients during induction and maintenance, respectively), mainly due to, often low grade, polyneuropathy. During maintenance 23% of patients received daratumumab alone. Global quality of life (QoL) improved significantly and was clinically relevant, which persisted during maintenance treatment. Interpretation: Ixazomib-Daratumumab-low-dose dexamethasone as first line treatment in intermediate-fit NDMM patients is safe and improves global QoL. However, efficacy was limited, partly explained by ixazomib-induced toxicity, hampering long term tolerability of this 3-drug regimen. This highlights the need for more efficacious and tolerable regimens improving the outcome in vulnerable intermediate-fit patients. Funding: Janssen Pharmaceuticals, Takeda Pharmaceutical Company Limited.</p

Living (World) Heritage Cities: An Introduction

Cities are in a constant process of change, which is ignited by the renegotiation of spaces, uses, needs, and values among their inhabitants, and by challenges brought by an increasingly globalized and complex world, such as multidiversity, inequality, pandemics, conflicts, and climate change, among others. Inevitably, these processes pose challenges to sustainable urban development and heritage conservation in Living (World) Heritage Cities. In the past three decades, the emergence of a living heritage approach to management and conservation promoted the empowerment of core communities in decision-making over the management of these changes and the preservation of their continuous relationship with their heritage for the mutual benefit of cities, heritage, and society. While research worldwide offers examples of best practices, the implementation of these approaches still faces many barriers and new challenges. This book aims to explore how (World) Heritage Cities are dealing with the preservation of their living heritage, what is needed for its effective management, what approaches are adopted, and what challenges and opportunities are encountered. Results offer an overview of current practices, which also include some of the first testimonies of their evolution in the time of a global pandemic, that can inform future research and urban strategies

Exploring Transformations in Caribbean Indigenous Social Networks through Visibility Studies : the Case of Late Pre-Colonial Landscapes in East-Guadeloupe (French West Indies)

This paper presents a study of the visual properties of natural and Amerindian cultural landscapes in late pre-colonial East-Guadeloupe and of how these visual properties affected social interactions. Through a review of descriptive and formal visibility studies in Caribbean archaeology, it reveals that the ability of visual properties to affect past human behaviour is frequently evoked but the more complex of these hypotheses are rarely studied formally. To explore such complex hypotheses, the current study applies a range of techniques: total viewsheds, cumulative viewsheds, visual neighbourhood configurations and visibility networks. Experiments were performed to explore the control of seascapes, the functioning of hypothetical smoke signalling networks, the correlation of these visual properties with stylistic similarities of material culture found at sites and the change of visual properties over time. The results of these experiments suggest that only few sites in Eastern Guadeloupe are located in areas that are particularly suitable to visually control possible sea routes for short- and long-distance exchange; that visual control over sea areas was not a factor of importance for the existence of micro-style areas; that during the early phase of the Late Ceramic Age networks per landmass are connected and dense and that they incorporate all sites, a structure that would allow hypothetical smoke signalling networks; and that the visual properties of locations of the late sites Morne Souffleur and Morne Cybèle-1 were not ideal for defensive purposes. These results led us to propose a multi-scalar hypothesis for how lines of sight between settlements in the Lesser Antilles could have structured past human behaviour: short-distance visibility networks represent the structuring of navigation and communication within landmasses, whereas the landmasses themselves served as focal points for regional navigation and interaction. We conclude by emphasising that since our archaeological theories about visual properties usually take a multi-scalar landscape perspective, there is a need for this perspective to be reflected in our formal visibility methods as is made possible by the methods used in this paper.publishe

Exploring Transformations in Caribbean Indigenous Social Networks through Visibility Studies: the Case of Late Pre-Colonial Landscapes in East-Guadeloupe (French West Indies)

This paper presents a study of the visual properties of natural and Amerindian cultural landscapes in late pre-colonial East-Guadeloupe and of how these visual properties affected social interactions. Through a review of descriptive and formal visibility studies in Caribbean archaeology, it reveals that the ability of visual properties to affect past human behaviour is frequently evoked but the more complex of these hypotheses are rarely studied formally. To explore such complex hypotheses, the current study applies a range of techniques: total viewsheds, cumulative viewsheds, visual neighbourhood configurations and visibility networks. Experiments were performed to explore the control of seascapes, the functioning of hypothetical smoke signalling networks, the correlation of these visual properties with stylistic similarities of material culture found at sites and the change of visual properties over time. The results of these experiments suggest that only few sites in Eastern Guadeloupe are located in areas that are particularly suitable to visually control possible sea routes for short- and long-distance exchange; that visual control over sea areas was not a factor of importance for the existence of micro-style areas; that during the early phase of the Late Ceramic Age networks per landmass are connected and dense and that they incorporate all sites, a structure that would allow hypothetical smoke signalling networks; and that the visual properties of locations of the late sites Morne Souffleur and Morne Cybèle-1 were not ideal for defensive purposes. These results led us to propose a multi-scalar hypothesis for how lines of sight between settlements in the Lesser Antilles could have structured past human behaviour: short-distance visibility networks represent the structuring of navigation and communication within landmasses, whereas the landmasses themselves served as focal points for regional navigation and interaction. We conclude by emphasising that since our archaeological theories about visual properties usually take a multi-scalar landscape perspective, there is a need for this perspective to be reflected in our formal visibility methods as is made possible by the methods used in this paper.Digital ArchaeologyArchaeology of the America