Real-world study of the efficacy and safety of belantamab mafodotin (GSK2857916) in relapsed or refractory multiple myeloma based on data from the nominative ATU in France: the IFM 2020-04 study

Belantamab mafodotin (BM) is an anti-BCMA antibody-drug conjugate (GSK2857916) that represents an alternative option in multiple myeloma. We sought to assess the efficacy and safety of BM in a real-world setting in patients who benefited from an early access program. We conducted an observational, retrospective, multicenter study. Eligibility criteria were treatment of relapsed or refractory multiple myeloma (RRMM) in monotherapy in adult patients who have received at least three lines of therapy previously, including at least one immunomodulatory agent (IMiD), a proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody, and whose disease progressed during the last treatment period. The primary endpoint of the study is to assess the overall survival (OS). Between November 2019 and December 2020, 106 patients were treated with BM; 97 were eligible for the efficacy evaluation and 104 for safety. The median age was 66 (range, 37–82) years. High-risk cytogenetics were identified in 40.9% of patients. Fifty-five (56.7%) patients were triple-class refractory and 11 (11.3%) were penta-class refractory. The median number of prior lines of treatment was five (range, 3–12). The median number of BM cycles administered was three (range, 1–22). The overall response rate at best response was 38.1% (37/97). The median OS was 9.3 months (95% confidence interval [CI]: 5.9-15.3), and median progression-free survival was 3.5 months (95% CI: 1.9-4.7). The median duration of response was 9 months (range, 4.65-10.4). Treatment was delayed for 55 (52.9%) patients including 36.5% for treatment-related toxicity. Ophthalmic adverse events, mainly grade ≤2, were the most common toxicity (48%). The occurrence of keratopathy was 37.5%. Overall, our data are concordant with the results from DREAMM-2 in terms of efficacy and safety on a non-biased population

Complexes de Ruthénium Bis-Terdentates pour la réalisation d'assemblages photoactivables

Ce mémoire est consacré à la synthèse et la caractérisation de complexes bis-terdentates de ruthénium pour leur potentielle utilisation dans des triades photosensibles, ou pour la fabrication de dispositifs photosensibles. La première partie se concentre sur les propriétés photophysiques de deux complexes de RuII bis-terdentates. Le premier est un complexe homoleptique, formé de ligands tridentates comprenant deux sous-unités carbène (CNC), le second est un complexe hétéroleptique composé d'un ligand CNC et d'une terpyridine. Ce complexe hétéroleptique est luminescent à température ambiante, contrairement à ses deux complexes parents homoleptiques. Les propriétés électrochimiques et photoélectrochimiques de complexes de type [M(tpy)2]2+ (M=FeII ou RuII), dont les ligands terpyridine sont substitués par des groupements thiols, sont étudiées dans une seconde partie. Ces complexes électropolymérisent de manière organisée sur des électrodes d'or, par oxydation des thiols en disulfures. Ces propriétés ont été utilisées pour construire des diades [RuII]-[FeII] sur des électrodes d'or, dont le photocourant a pu être mesuré. Dans le dernier chapitre, les propriétés photophysiques et d'électropolymérisation du complexe de ruthénium décrit dans le chapitre 2 sont utilisées pour tenter de fabriquer un transistor pho-toactivable.This thesis deals with the synthesis and characterization of several bis-terdentate complexes, and their potential use for the construction of photoactive molecular triads, or the fabrication of photoactive devices. The first chapter focuses on the photophysical properties of two new bis-terdentate RuII com-plexes. The first one is a homoleptic complex containing two N-heterocyclic carbene-based ligands (CNC) allowing close-to-perfect octahedral coordination geometry. The second one is a heteroleptic complex bearing a CNC ligand and an ancillary terpyridine ligand. This second complex displays room temperature luminescence whereas both homoleptic terpyridine-based and CNC-based RuII complexes are only luminescent at 77 K. The second chapter describes the electrochemical properties of a [M(tpy)2]2+-type (M = RuII or FeII) complex bearing thiol groups on both of the terpyridines are described. These complexes display electropolymerization properties through oxidation of thiols into disulfides. This phenomenon happens only on gold, suggesting that the polymer chains organize on the surface of the electrodes. Moreover, self-assembled monolayers of the RuII complexes were formed on gold, and their ability to exchange charges with the electrode upon irradiation was studied. Finally, self-organisation and electropolymerization properties were used to form [RuII]-[FeII] diads on a gold surface, and their photoresponse was recorded. The last chapter describes the attempts to construct a molecular photosensitive device by electropolymerizing the RuII complexes depicted in the second chapter in nanogaps between gold electrodes.SAVOIE-SCD - Bib.électronique (730659901) / SudocGRENOBLE1/INP-Bib.électronique (384210012) / SudocGRENOBLE2/3-Bib.électronique (384219901) / SudocSudocFranceF

Gestion des écosystèmes pâturés en situations extensives : apports de l'écologie fonctionnelle et perspectives de recherches appliquées en moyenne montagne humide

International audienc

Photochemical Tuning of Tris-Bidentate Acridine- and Phenazine-Based Ir(III) Complexes

International audienc

Light‐Induced Ejection of a Tridentate Ligand from a Ruthenium(II) Complex

International audienc

Synthesis of an Electrodeficient Dipyridylbenzene-like Terdentate Ligand: Cyclometallating Ligand for Highly Emitting Iridium(III) and Platinum(II) Complexes

Cyclometallated iridium(III) and platinum(II) complexes are intensely used in optoelectronics for their photophysical properties and ability to convert excitons from singlet to triplet state, thus improving the device efficiency. In this contribution, we report the multi-steps synthesis of an electrodeficient dipyridylbenzene-like terdentate ligand [N^C^N], namely 2′,6′-dimethyl-2,3′:5′,2″-terpyridine (6), with 18% overall yield. Compound 6 has been employed to synthesize two phosphorescent complexes of platinum(II) and iridium(III), namely compounds 7 and 8, respectively. Both complexes have been characterized by NMR and high resolution mass spectrometry, and demonstrate high luminescence quantum yields in a deaerated solution at room temperature, with 18% and 61% for 7 and 8, respectively. If the iridium(III) complex displays similar emission properties to [Ir(dpyx)(ppy)Cl] (dpyx = 3,5-dimethyl-2,6-dipyridylbenzene and ppy = 2- phenylpyridine), the platinum(II) derivative, with λem = 470 nm, is a rare example of a fluorine atom-free blue emitting [N^C^N]PtCl complex

Towards mismatched DNA photoprobes and photoreagents: “elbow-shaped” Ru(ii) complexes

info:eu-repo/semantics/publishe

Photochromic and Redox Properties of Bisterpyridine Ruthenium Complexes Based on Dimethyldihydropyrene Units as Bridging Ligands

International audienc

Does extensification of rich grasslands alter the C and N cycles, directly or via species composition?

International audienceExtensification modify the C and N cycles in grassland ecosystems, but it is not clear whether reduced exploitation increases or decreases soil nitrogen availability, and whether these changes result from a direct effect of the treatment or from an indirect treatment effect through a change in plant species composition. A formerly intensively exploited grassland was submitted to the following treatments: (i) control with one mowing and four grazing periods per year (4G+M), (ii) cessation of mowing (4G), (iii) cessation of mowing and suppression of three grazing periods (1G). During the 13th year of the experiment, the species composition and key indicators of the C and N cycles were measured, using 20 samples per treatment. Lolium perenne and Trifolium repens disappeared in favor of tall caespitose grasses in 4G, and of rhizomatous species in 1G. The species composition and the nitrate concentration of the soil solution suggested an increase in nutrient availability under reduced exploitation, whereas the nitrification and denitrification potentials decreased. More particulate organic matter accumulated in proportion to the below-ground phyto-mass, whereas the C:N ratio remained constant. Testing treatment effect at similar species composition and plant community effect within the same treatment showed that: (1) the increase in POM residence time was mainly due to the changes in species composition, (2) the decrease in nitrification activity resulted mainly from a direct effect of the treatment, and (3) a compensation between a direct positive and an indirect negative effect of the treatment resulted in no change in extractable N. All results suggested that soil N availability was not decreased, although litter degradability decreased. (c) 2004 Elsevier GmbH. All rights reserved