Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma : Long-Term Results of the PRIMA Study

PURPOSE The PRIMA study (ClinicalTrials.gov identifier: NCT00140582) established that 2 years of rituximab maintenance after first-line immunochemotherapy significantly improved progression-free survival (PFS) in patients with follicular lymphoma compared with observation. Here, we report the final PFS and overall survival (OS) results from the PRIMA study after 9 years of follow-up and provide a final overview of safety. METHODS Patients (> 18 years of age) with previously untreated high-tumor-burden follicular lymphoma were nonrandomly assigned to receive one of three immunochemotherapy induction regimens. Responding patients were randomly assigned (stratified by induction regimen, response to induction treatment, treatment center, and geographic region) 1:1 to receive 2 years of rituximab maintenance (375 mg/m(2), once every 8 weeks), starting 8 weeks after the last induction treatment, or observation (no additional treatment). All patients in the extended follow-up provided their written informed consent (data cutoff: December 31, 2016). RESULTS In total, 1,018 patients completed induction treatment and were randomly assigned to rituximab maintenance (n = 505) or observation (n = 513). Consent for the extended follow-up was provided by 607 patients (59.6%) of 1,018 (rituximab maintenance, n = 309; observation, n = 298). After data cutoff, median PFS was 10.5 years in the rituximab maintenance arm compared with 4.1 years in the observation arm (hazard ratio, 0.61; 95% CI, 0.52 to 0.73; P <.001). No OS difference was seen in patients randomly assigned to rituximab maintenance or observation (hazard ratio, 1.04; 95% CI, 0.77 to 1.40; P = .7948); 10-year OS estimates were approximately 80% in both study arms. No new safety signals were observed. CONCLUSION Rituximab maintenance after induction immunochemotherapy provides a significant long-term PFS, but not OS, benefit over observation.Peer reviewe

Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma

[Excerpt] Multiple myeloma (MM) is the third most common hematological malignancy, after Non-Hodgkin Lymphoma and Leukemia. MM is generally preceded by Monoclonal Gammopathy of Undetermined Significance (MGUS) [1], and epidemiological studies have identified older age, male gender, family history, and MGUS as risk factors for developing MM [2]. The somatic mutational landscape of sporadic MM has been increasingly investigated, aiming to identify recurrent genetic events involved in myelomagenesis. Whole exome and whole genome sequencing studies have shown that MM is a genetically heterogeneous disease that evolves through accumulation of both clonal and subclonal driver mutations [3] and identified recurrently somatically mutated genes, including KRAS, NRAS, FAM46C, TP53, DIS3, BRAF, TRAF3, CYLD, RB1 and PRDM1 [3,4,5]. Despite the fact that family-based studies have provided data consistent with an inherited genetic susceptibility to MM compatible with Mendelian transmission [6], the molecular basis of inherited MM predisposition is only partly understood. Genome-Wide Association (GWAS) studies have identified and validated 23 loci significantly associated with an increased risk of developing MM that explain ~16% of heritability [7] and only a subset of familial cases are thought to have a polygenic background [8]. Recent studies have identified rare germline variants predisposing to MM in KDM1A [9], ARID1A and USP45 [10], and the implementation of next-generation sequencing technology will allow the characterization of more such rare variants. [...]French National Cancer Institute (INCA) and the Fondation Française pour la Recherche contre le Myélome et les Gammapathies (FFMRG), the Intergroupe Francophone du Myélome (IFM), NCI R01 NCI CA167824 and a generous donation from Matthew Bell. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD018522. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank the Association des Malades du Myélome Multiple (AF3M) for their continued support and participation. Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organizatio

Sur la route de l îlot de stabilité superlourd (Spectroscopie prompte des noyaux 246Fm et 256Rf)

La région des noyaux transfermium (Z = 100 à 104) est la dernière région de la charte nucléaire accessible en spectroscopie. Elle donne ainsi les ultimes points d'ancrage pour les modèles. Elle se situe en outre sur les chaînes de décroissance a des noyaux superlourds. Cette région se situe à la limite des capacité de mesures spectroscopiques actuelles. Elle demande donc des développements technologiques pour passer ces limites. Ma thèse porte sur différents aspects de la spectroscopie des noyaux de la région transfermium. J'ai participé au développement des cartes d'acquisition numériques TNT2D pour détecteurs germanium. J'ai validé leur utilisation sur le spectromètre gamma JUROGAM et quantifié le gain apporté par rapport à un système d'acquisition analogique. Ces tests entraient dans la préparation de l'expérience visant l'étude spectroscopique prompte du noyau 256Rf. Cela m'a également amené à travailler au développement d'un faisceau de 5ari isotopique. Dans cette optique, j'ai étudié et testé l'utilisation de composés organométalliques du titane compatible avec la technique MIVOC. J'ai en parallèle étudié l'utilisation de pastilles de titane métallique ou de dioxyde de titane au moyen d'un four à induction nouvellement développé à l'Université de Jyvaskylà Ces développements nous permettront prochainement d'effectuer l'étude en spectroscopie prompte du 256Rf. En parallèle à ces développement, j'ai eu la chance d'étudier en spectroscopie prompte le noyau 246Fm à l'Université de Jyvaskyla. Les mesures ont permis de mettre en évidence la bande rotationnelle basée sur le niveau fondamental du 246Fm. Cette bande a été observée jusqu'au niveau 16+ et présente un comportement assez similaire aux isotopes pair-pairs voisins hormis le haut de la bande pour lequel une statistique plus forte serait nécessaire pour conclure.The region of transfermium nuclei (Z = 100 to 104) is the last region of the nuclides chart to be accessible to spectroscopie measurements. It therefore provides the ultimate anchor points for nuclear models. This region also lies on the path of the alpha-decay chains of the super- heavy elements. This region represents the limit of today's spectroscopie capabilities. It therefore requires technological developments in order to overcome these limits. My thesis focuses on various aspects of the spectroscopy of transfermium nuclei. 1 took part in the development of the TNT2D digital acquisition cards for germanium detectors. 1 validated their use on the gamma-ray spectrometer JUROGAM during an in-beam experiment and demonstrated the gain compared to an analogue acquisition system . These tests were part of the developments needed to secure a study of the prompt spectroscopy of 2s6Rf. The preparation of this experiment also lead me to work on the development of a sOTi beam. For that purpose, 1 studied and tested the use of titanium organo-metallic compounds compatible with the MIVOC technique. In parallel , 1 studied the use of metallic and oxyde titanium pellets with an inductive oven newly developed at the University of Jyvaskyla. ln addition to the se developments, 1 had the opportunity to study the in- beam prompt spectroscopy of 246Fm at the University of Jyvaskyla. The measurements yielded a rotational band built on the ground state of 246Fm. This band has been observed up to the level 16+ and shows a behaviour quite similar to the neighbouring even - even isotopes, except for the top of the band for which a wider statistics is necessary in order to conclude.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Spectroscopie de noyaux très lourds en vue de l'étude des noyaux super-lourds

Grâce aux avancées techniques de ces dernières années, l'étude des orbitales nucléoniques des noyaux très lourds (VHE) est devenue aujourd'hui possible et nous permet, par le biais de la déformation, de nous renseigner sur la structure nucléaire des noyaux superlourds (SHE). Ce travail de thèse a précisément pour objectif l'étude spectroscopique des noyaux lourds et très lourds. Les difficultés expérimentales liées à ce type de mesures, nous ont amenés dans le cadre de cette thèse, à mener une étude détaillée d'optimisation et prospection dans la région VHE. Ainsi, on a cherché à optimiser l'épaisseur de cible pour une productiondétection maximale en tenant compte des différents paramètres entrant en jeu : la section efficace, l'intensité de faisceau, l'ouverture angulaire des séparateurs et le straggling angulaire dans la cible, dû à l'évaporation de neutrons et aux déflections Coulombienne du noyau de recul. Une vaste étude de prospection dans la région VHE a également été réalisée sur la base de sections efficaces publiées ou non, et de simulations effectuées à l'aide du code statistique HIVAP. En parallèle à ce travail, l'extension possible du domaine de validité d'un jeu de paramètres HIVAP a été étudiée. Ce travail nous a permis de dégager une liste d'expériences d'intérêt pour la production des noyaux VHE. On s'est notamment consacré à l'étude des noyaux 256No et 256Rf pour lesquels deux propositions d'expériences ont été acceptées. La déformation octupolaire prédite dans la région des actinides est abordée dans une autre partie de cette thèse, consacrée à la spectroscopie gamma du Protactinium 223. Les résultats de cette nouvelle expérience réalisée auprès de JUROGAM sont analysés et comparés aux résultats antérieurs confirmant ainsi la structure octupolaire de ce noyau.Within the recent years, the spectroscopic study of single particle orbitals of very heavy elements (VHE) became possible with the development of increasingly efficient experimental setups. This allow us, through nuclear deformation, to access in with these deformed nuclei to orbitals situated around the Fermi level in the spherical superheavy elements (SHE) and learn more about the nuclear structure of these nuclei. The aim of this work is the spectroscopic studies of heavy and very heavy elements. Because of the experimental difficulties associated with the fusion reactions in the VHE region, a detailed optimization studies is essential. Simulation of energy loss and angular straggling of these nuclei due to the interaction in the target and to neutron's evaporation was carried out and allowed us to optimize the angular acceptance of the separators according to the target thickness. An extensive survey and exploration in the VHE region was also conducted on the basis of cross section's systematics in the literature and simulations carried out using the statistical code HIVAP. In this framework, the possible extension of the range of validity of a set of HIVAP parameters was investigated. This work has enabled us to prepare a list of experiments of interest for the production of very heavy nuclei. In this thesis, our work was concentrated on the spectroscopy of the nuclei 256No et 256Rf for which two experimental proposals were accepted. The octupole deformations predicted in the actinides region is studied in another part of this thesis, a part witch is dedicated to the gamma spectroscopy of 223Pa. The data from a new experiment carried out using the JUROGAMRITUGREAT setup are analysed and compared to previous results. They confirm the octupole deformed shape in this nucleus.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Magnetic Field Computation for PMTs Shielding Optimization

International audienceThe Photon Array for the studies of Radioactive and Ion Stable beams (PARIS) is a multidetector of clusters. Each cluster is composed of 9 units of two-shells phoswiches of LaBr3/NaI scintillators optically coupled to one photomultiplier tube. PARIS will be used in combination with the VAMOS spectrometer at GANIL. During the experiment, PMTs will be exposed to the constant magnetic fringe fields produced by a quadrupole. Magnetic shielding is essential to efficiently lower the magnetic field inside the PMTs. The design and the optimization of this shield is presented. A comparison is done between the simulated and the experimental values

Angular correlations in the prompt neutron emission in spontaneous fission of 252Cf

An experiment aiming at the detailed investigation of angular correlations in the neutron emission from spontaneous fission of 252Cf has been performed at IPHC Strasbourg using the angle-sensitive double ionization chamber CODIS for measuring fission fragments and a set of 60 DEMON scintillator counters for neutron detection. The main aim of the experiment is to search for an anisotropy of neutron emission in the center-of-mass system of the fragments. The present status of the data analysis and the full Monte-Carlo simulation of the experiment are reported in the present paper

BAM conditioning before autologous transplantation for lymphoma: a study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)

International audienc

Carfilzomib Weekly Plus Melphalan and Prednisone in Newly Diagnosed Elderly Multiple Myeloma (IFM 2012-03) / 57th Annual Meeting of the American-Society-of-Hematology - Orlando, FL

WOS:000368020103223International audienceConference: 57th Annual Meeting of the American-Society-of-Hematology - Orlando, FL - DEC 05-08, 201