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The purpose of this article is to examine the influence of professionalization and mediatization of rugby on the representations of masculinity in this sport over the last quarter century. Data used for both statistical analysis (using chi-square tests of independence and Multiple Correspondence Analysis) and qualitative content analysis were collected in France through a corpus of 799 rugby-related advertisements mainly dating from 1987 to 2015. The authors demonstrate that, alongside the hegemonic masculinity produced by the socialization of rugby players until the 1980s (the ``Beast''), the marketization of elite rugby that began in the 1990s has led to the emergence of an alternative figure of masculinity that values aesthetics over physical strength (the ``Beefcake''). The authors theorize this hybridization as a way for rugby players, who follow the lead of advertisers and communications agencies, to distance themselves from the increasingly stigmatized figure of masculinity embodied by their sport in order to entice new audiences. Simultaneously, while allowing them to seize the financial manna of advertising, this rebranding reveals the plasticity of the hegemonic masculinity conveyed by rugby, which is able to regenerate itself by evolving with the times. Based on this case, the authors then discuss the dialectic relationship between the hegemonic model and hybrid masculinities in both a synchronic and a diachronic perspective.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma most reported in Asia. We performed a comprehensive clinical, pathological and genomic study of 71 European MEITL patients (36 males, 35 females, median age 67 years). The majority presented with gastrointestinal involvement and had emergency surgery, and 40% had stage IV disease. The tumors were morphologically classified into two groups: typical (58%) and atypical (i.e., non-monomorphic or with necrosis, angiotropism or starry-sky pattern) (42%), sharing a homogeneous immunophenotypic profile (CD3+ [98%] CD4- [94%] CD5- [97%] CD7+ [97%] CD8+ [90%] CD56+ [86%] CD103+ [80%] cytotoxic marker+ [98%]) with more frequent expression of TCRgd (50%) than TCRab (32%). MYC expression (30% of cases) partly reflecting MYC gene locus alterations, correlated with non-monomorphic cytology. Almost all cases (97%) harbored deleterious mutation(s) and/or deletion of the SETD2 gene and 90% had defective H3K36 trimethylation. Other frequently mutated genes were STAT5B (57%), JAK3 (50%), TP53 (35%), JAK1 (12.5%), BCOR and ATM (11%). Both TP53 mutations and MYC expression correlated with atypical morphology. The median overall survival (OS) of 63 patients (43/63 only received chemotherapy after initial surgery) was 7.8 months. Multivariate analysis found a strong negative impact on outcome of MYC expression, TP53 mutation, STAT5B mutation and poor performance status while aberrant B-cell marker expression (20% of cases) correlated with better survival. In conclusion, MEITL is an aggressive disease with resistance to conventional therapy, predominantly characterized by driver gene alterations deregulating histone methylation and JAK/STAT signaling and encompasses genetic and morphologic variants associated with very high clinical risk.

PURPOSE The AHL2011 study (ClinicalTrials.gov identifier: NCT01358747 ) demonstrated that a positron emission tomography (PET)-driven de-escalation strategy after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) provides similar progression-free survival (PFS) and overall survival (OS) and reduces early toxicity compared with a nonmonitored standard treatment. Here, we report, with a prolonged follow-up, the final study results. METHODS Patients with advanced Hodgkin lymphoma (stage III, IV, or IIB with mediastinum/thorax ratio > 0.33 or extranodal involvement) age 16-60 years were prospectively randomly assigned between 6 × BEACOPP and a PET-driven arm after 2 × BEACOPP delivering 4 × ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in PET2– and 4 × BEACOPP in PET2+ patients. PET performed after four cycles of chemotherapy had to be negative to complete the planned treatment. RESULTS In total, 823 patients were enrolled including 413 in the standard arm and 410 in the PET-driven arm. With a 67.2-month median follow-up, 5-year PFS (87.5% v 86.7%; hazard ratio [HR] = 1.07; 95% CI, 0.74 to 1.57; P = .67) and OS (97.7% in both arms; HR = 1.012; 95% CI, 0.50 to 2.10; P = .53) were similar in both randomization arms. In the whole cohort, full interim PET assessment predicted patients' 5-year PFS (92.3% in PET2–/PET4–, 75.4% [HR = 3.26; 95% CI, 18.3 to 5.77] in PET2+/PET4– and 46.5% [HR = 12.4; 95% CI, 7.31 to 19.51] in PET4+ patients, respectively; P < .0001) independent of international prognosis score. Five-year OS was also affected by interim PET results, and PET2+/PET4– patients (93.5%; HR = 3.3; 95% CI, 1.07 to 10.1; P = .036) and PET4+ patients (91.9%; HR = 3.756; 95% CI, 1.07 to 13.18; P = .038) had a significant lower OS than PET2–/PET4– patients (98.2%). Twenty-two patients (2.7%) developed a second primary malignancy, 13 (3.2%) and 9 (2.2%) in the standard and experimental arms, respectively. CONCLUSION The extended follow-up confirms the continued efficacy and favorable safety of AHL2011 PET-driven strategy, which is noninferior to standard six cycles of BEACOPP. PET4 provides additional prognostic information to PET2 and allows identifying patients with particularly poor prognosis.

Purpose: Patients with Relapsed or Refractory (R/R) Peripheral T cell Lymphomas (PTCL) have a poor prognosis. Bendamustine (B) and Brentuximab Vedotin (Bv) have shown interesting results in this setting. However, little information is available about their efficacy in combination. Patients and Methods: This multicenter and retrospective study aimed to evaluate the efficacy and safety of the combination of BBv in patients with non-cutaneous R/R PTCL among 21 LYSA centers in France and Belgium. The primary objective was the overall response rate. Results: Eighty-two patients with R/R PTCL were included. The best ORR was 68%, with 49% of patients in CR. In multivariable analysis, only the relapse status after the last regimen (relapse vs refractory) was associated with the response with an ORR of 83% vs 57% (OR=3.70 (95%CI:1.3-10.5); p=0.014). Median DoR was 15.4 (0.6-50.2) months for patients in CR. With a median follow-up of 22 (0-52) months, the median PFS and OS were 8.3 and 26.3 months respectively. Moreover, patients in CR, who underwent an allogeneic transplant, had a better outcome than patients who did not with a median PFS and OS of 19.3 versus 4.8 months (p=0.0005) and NR versus 12.4 months (p=0.0013) respectively. Fifty-nine percent of patients experienced grade 3/4 adverse events which were mainly hematologic. Conclusion: BBv is highly active in patients with R/R PTCL and should be considered as a one of the best option of immunochemotherapy salvage combination in this setting and particularly as a bridge to allogeneic transplant for eligible patients.

Les auteurs proposent une analyse de l’implication des sociétés de capital-investissement (SCI) dans la croissance organisationnelle de leurs participations en étudiant les mécanismes de gouvernance mis en œuvre dans les opérations d’acquisition à effet de levier dans lesquelles une stratégie de consolidation sectorielle (build-up) est déployée. À l’aide d’une revue de la littérature sur la gouvernance des build-up et d’une étude de cas approfondie, ils identifient les variables clés de la gouvernance de ces opérations.

Rituximab plus polychemotherapy is the standard of care in diffuse large B-cell lymphoma (DLBCL). GAINED, a randomized phase 3 trial, compared obinutuzumab to rituximab. Transplant-eligible patients (18-60 years) with an untreated age-adjusted International Prognostic Index (aaIPI) score ≥1 DLBCL were randomized (1:1) between obinutuzumab or rituximab and stratified by aaIPI (1; 2-3) and chemotherapy regimen (doxorubicin, cyclophosphamide, prednisone plus vindesine, bleomycin [ACVBP] or vincristine [CHOP]). Consolidation treatment was determined according to response to interim positron emission tomography (PET). Responders after cycle 2 and 4 (PET2−/PET4−) received immunochemotherapy. Responders after only cycle 4 (PET2+/4−) received transplantation. The primary objective was an 8% improvement (hazard ratio [HR] = 0.73; 80% power; α risk, 2.5%; 1-sided) in 2-year event-free survival (EFS) in the obinutuzumab arm. From September 2012, 670 patients were enrolled (obinutuzumab, n = 336; rituximab, n = 334). A total of 383 (57.2%) were aaIPI 2-3, 339 (50.6%) received CHOP. Median follow-up was 38.7 months. The 2-year EFS was similar in both groups (59.8% vs 56.6%; P = .123; HR = 0.88). The 2-year PFS in the whole cohort was 83.1% (95% confidence interval, 80% to 85.8%). PET2−/4− and PET2+/4− had similar 2-year progression-free survival (PFS) and overall survival (OS): 89.9% vs 83.9% and 94.8% vs 92.8%. The 2-year PFS and OS for PET4+ patients were 62% and 83.1%. Grade 3-5 infections were more frequent in the obinutuzumab arm (21% vs 12%). Obinutuzumab is not superior to rituximab in aaIPI ≥1 DLBCL transplant-eligible patients. This trial was registered at www.clinicaltrials.gov as #NCT01659099.

Nous mettons en evidence un accroissement des liquidites moyennes detenues par les societes cotees de l’Eurozone entre 1986 et 2015. Cet accroissement est principalement du a un saut significatif a la fin des annees 1990 lie a une modification soudaine de la population des societes cotees (effet de selection). Nous observons notamment une augmentation de la proportion de firmes intensives en R&D, dotees de fortes perspectives de croissance et fortement detentrices de liquidites. La plupart de ces entreprises appartiennent aux secteurs de la sante et de la technologie et semblent avoir beneficie de conditions favorables d’introduction en bourse durant cette periode. Ni les changements des caracteristiques des entreprises, ni ceux de leurs politiques de tresorerie, n’expliquent de facon significative la tendance observee (absence d’effet intra-population). Les differences de niveaux de liquidites moyens entre pays de l’Eurozone sont principalement expliquees par les differences de proportions de firmes intensives en R&D, et non par les differences d’environnements juridiques ou financiers.

International audience; Simple Summary Patients with relapsing/refractory B-cell lymphoma who respond to a platinum salt-based salvage regimen can be cured after therapy intensification followed by autologous stem cell transplantation. The Bruton tyrosine kinase inhibitor ibrutinib, given alone or in association with other molecules, has proven effective in numerous B-cell lymphomas. The aim of the current study was to evaluate the safety of the combination of ibrutinib, rituximab, dexamethasone, and cytarabine with either cisplatin (R-DHAP) or oxaliplatin (R-DHAOx), with ibrutinib given based on a prespecified dose-escalation design. The concomitant combination of ibrutinib and R-DHAP resulted in limiting hematological, infectious, and renal toxicities. As a result, the maximum ibrutinib dose could not be administered. On the other hand, when the ibrutinib administration schedule was combined with R-DHAOx, ibrutinib dosing could be increased up to the maximum prespecified dose but with relevant toxicities. Despite a strong rationale for combining ibrutinib with either R-DHAP or R-DHAP/Ox, this approach was limited by significant toxicities. In the post-rituximab era, patients with relapsed/refractory non-Hodgkin B-cell lymphoma (R/R B-NHL) responding to a platinum salt-based salvage regimen can potentially be cured after intensification followed by autologous stem cell transplantation, with the quality of the response to salvage predicting survival. The Bruton tyrosine kinase inhibitor ibrutinib, given as monotherapy or combined with other molecules, has proven effective in numerous B-cell lymphomas. To evaluate the safety of the combination of ibrutinib, rituximab, dexamethasone, and cytarabine with either cisplatin (R-DHAP) or oxaliplatin (R-DHAOx), we conducted a multicenter Phase 1b-II study in transplant-eligible R/R B-NHL patients, with ibrutinib given using a 3-by-3 dose-escalation design. The combination of R-DHAP and ibrutinib (given from Day 1 to Day 21 of each cycle) was associated with dose-limiting hematological, infectious, and renal toxicities, while we were unable to reach a dose to recommend for Phase II. R-DHAOx could only be combined with a daily dosage of 280 mg ibrutinib when administered continuously. R-DHAP combined with intermittent ibrutinib administration (from Day 5 to Day 18) was found to be highly toxic. On the other hand, when this administration schedule was combined with R-DHAOx, ibrutinib dosing could be increased up to 560 mg but with relevant toxicities. Despite a strong rationale for combining ibrutinib and R-DHAP/R-DHAOx, as both target lymphoma B-cells by different mechanisms, this approach was limited by significant toxicities.

International audience; For the understanding of severe accidents in sodium cooled fast reactors (SFR), it is necessary to understand two prototypic accident scenarios such as ULOF (Unprotected Loss of Flow Accident) and UTOP (Unprotected Transient OverPower). As the base knowledge, it is also important to understand high temperature chemical interaction among major core materials such as MOx fuel (MOx: mixed oxide of uranium and plutonium), steel cladding and B4C neutron absorber have to be investigated. This study aims at providing experimental data on phase formation and phase-stability at various temperature and pressure conditions. A first series of samples containing a mixture of B4C and steel were prepared to obtain a homogenous metallic solid. In a second step, these metallic samples were mixed and melted with small UO2 pieces by arc melting. Then these samples underwent a heat treatment at 1900 °C for 1 hour. EDS, EBSD and EPMA analyses were performed to identify the phases formed during the solidification. In addition, thermodynamic calculations were performed for the interpretation of the results, revealing that a carbo-reduction reaction occurs: UO2 + 2 C = 2 CO + U. A significant amount of uranium from the fuel is dissolved in the metallic liquid phase, leading to the formation of mixed borides (UM3B2, UMB4, UM4B, M=Fe,Cr,Ni). In comparison with the UO2/steel interaction, the present results show that the presence of B and C in the melt improves the wetting behaviour of the metallic liquid towards UO2.

Primary mediastinal B-cell lymphoma (PMBL) is a rare type of aggressive lymphoma typically affecting young female patients. The first-line standard of care remains debated. We performed a large multicenter retrospective study in 25 centers in France and Belgium to describe PMBL patient outcomes after first-line treatment in real-life settings. A total of 313 patients were enrolled and received rituximab (R) plus ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone) (n = 180) or CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) delivered every 14 days (R-CHOP14, n = 76) or 21 days (R-CHOP21, n = 57) and consolidation strategies in modalities that varied according to time and institution, mainly guided by positron emission tomography. Consolidation autologous stem cell transplantation was performed for 46 (25.6%), 24 (31.6%), and 1 (1.8%) patient in the R-ACVBP, R-CHOP14, and R-CHOP21 groups, respectively (P < .001); only 17 (5.4%) patients received mediastinal radiotherapy. The end-of-treatment complete metabolic response rates were 86.3%, 86.8%, and 76.6% (P = .23) in the R-ACVBP, R-CHOP14, and R-CHOP21 groups. The median follow-up was 44 months, and the R-ACVBP, R-CHOP14, and R-CHOP21 three-year progression-free survival probabilities were 89.4% (95% confidence interval [CI], 84.8-94.2), 89.4% (95% CI, 82.7-96.6), and 74.7% (95% CI, 64-87.1) (P = .018). A baseline total metabolic tumor volume (TMTV) ≥360 cm3 was associated with a lower progression-free survival (hazard ratio, 2.18; 95% CI, 1.05-4.53). Excess febrile neutropenia (24.4% vs 5.3% vs 5.3%; P < .001) and mucositis (22.8% vs 3.9% vs 1.8%; P < .001) were observed with R-ACVBP compared with the R-CHOP regimens. Patients with PMBL treated with dose-dense immunochemotherapy without radiotherapy have excellent outcomes. R-ACVBP acute toxicity was higher than that of R-CHOP14. Our data confirmed the prognostic importance of baseline TMTV.

Nodal peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) with cytotoxic phenotype is overall rare, with most reports coming from Asia. Given its elusive pathobiology, we undertook a clinicopathological and molecular study of 54 Western patients diagnosed with PTCL, NOS expressing cytotoxic molecules, within a lymph node. More commonly males (M/F-2,6/1) with median age of 60 years were affected. Besides lymphadenopathy, 87% of patients had ≥1 involved extranodal site. High-stage disease (III-IV), International Prognostic Index2, B symptoms, LDH level, and cytopenia(s) were observed in 92, 63, 67, 78, and 66% of cases, respectively. Ten patients had a history of B-cell malignancies, one each of myeloid neoplasm, breast or prostate cancer, and 4 others had underlying immune disorders. Most patients (70%) died, mostly of disease, with a median overall survival of 12.7 months. Immunophenotypically, the neoplastic lymphocytes were T-cell receptor (TCR) αβ + (47%), TCR-silent (44%) or TCRγδ+ (10%), commonly CD8 + (45%) or CD4-CD8- (32%). All except one had an activated cytotoxic profile, and 95% were subclassified into PTCL-TBX21 subtype based on CXCR3, TBX21, and GATA3 expression pattern. Seven patients (13%) disclosed EBER + tumor cells. Targeted DNA deep-sequencing (33 cases) and multiplex ligation-dependent reverse transcription-polymerase chain reaction assay (43 cases) identified frequent mutations in epigenetic modifiers (73%), including TET2 (61%) and DNMT3A (39%), recurrent alterations affecting the TCR (36%) and JAK/STAT (24%) signaling pathways and TP53 mutations (18%). Fusion transcripts involving VAV1 were identified in 6/43 patients (14%). Patients with nodal cytotoxic PTCL, NOS have an aggressive behavior and frequently present in a background of impaired immunity, although the association with Epstein-Barr virus is rare. The recurrent alterations in genes involved in DNA methylation together with genes related to cytokine or TCR signaling, suggest that co-operation of epigenetic modulation with cell-signaling pathways plays a critical role in the pathogeny of these lymphomas.

Summary Background Lenalidomide plus rituximab is approved to treat patients with relapsed or refractory follicular lymphoma. Obinutuzumab has been shown to enhance antibody-dependent cellular cytotoxicity, phagocytosis, and direct B-cell killing better than rituximab. Our aim was to determine the activity and safety of lenalidomide plus obinutuzumab in previously treated patients with relapsed or refractory follicular lymphoma. Methods In this multicentre, single-arm, phase 2 study, patients were enrolled from 24 Lymphoma Academic Research Organisation centres in France. Eligible patients (age ≥18 years) had histologically confirmed CD20-positive relapsed or refractory follicular lymphoma of WHO grade 1, 2, or 3a; an ECOG performance status of 0–2; and received at least one previous rituximab-containing therapy. Patients received oral lenalidomide (20 mg) plus intravenously infused obinutuzumab as induction therapy (1000 mg; six 28-day cycles), 1-year maintenance with lenalidomide (10 mg; 12 28-day cycles; days 2–22) plus obinutuzumab (1000 mg; alternate cycles), and 1-year maintenance with obinutuzumab (1000 mg; six 56-day cycles; day 1). The primary endpoint was the proportion of patients who achieved an overall response at induction end as per investigator assessment using the 1999 international working group criteria. The secondary endpoints were event-free survival, progression-free survival, overall survival, and safety. Analyses were per-protocol; the efficacy population included all patients who received at least one dose of both obinutuzumab and lenalidomide, and the safety population included all patients who received one dose of either investigational drug. The study is registered with ClinicalTrials.gov , number NCT01582776 , and is ongoing but closed to accrual. Findings Between June 11, 2014, and Dec 18, 2015, 89 patients were recruited and 86 patients were evaluable for efficacy and 88 for safety. Median follow-up was 2·6 years (IQR 2·2–2·8). 68 (79%) of 86 evaluable patients (95% CI 69–87) achieved an overall response at induction end, meeting the prespecified primary endpoint. At 2 years, event-free survival was 62% (95% CI 51–72), progression-free survival 65% (95% CI 54–74), duration of response 70% (95% CI 57–79), and overall survival 87% (95% CI 78–93). Complete response was achieved by 33 (38%, 95% CI 28–50) of 86 patients at induction end, and the proportion of patients achieving a best overall response was 70 (81%, 95% CI 72–89) and 72 (84%, 74–91) of 86 patients during induction and treatment, respectively. The most common adverse events were asthenia (n=54, 61%), neutropenia (n=38, 43%), bronchitis (n=36, 41%), diarrhoea (n=35, 40%), and muscle spasms (n=34, 39%). Neutropenia was the most common toxicity of grade 3 or more; four (5%) patients had febrile neutropenia. 57 serious adverse events were reported in 30 (34%) of 88 patients. The most common serious adverse events were basal cell carcinoma (n=5, 6%), febrile neutropenia (n=4, 5%), and infusion-related reaction (n=3, 3%). One patient died due to treatment-related febrile neutropenia. Interpretation Our data shows that lenalidomide plus obinutuzumab is active in previously treated patients with relapsed or refractory follicular lymphoma, including those with early relapse, and has a manageable safety profile. Randomised trials of new immunomodulatory regimens, such as GALEN or using GALEN as a backbone, versus lenalidomide plus rituximab, are warranted. Funding Lymphoma Academic Research Organisation, and Celgene and Roche

International audience; In most conventional optical experiments on substrate-supported nanoparticles, detectors are located in the far-field space whereas their intrinsic properties (scattering, absorption cross sections) are commonly computed in the near-field by using numerical approaches. In this respect, a connection between experiment and theory can be usefully made on the basis of the generalized optical theorem (GOT) that gives access, from the far-field expansion of the scattered wave, to the total extinction cross section as the sum of “forward” and “backward” contributions related to the power changes of the waves respectively transmitted and reflected by the substrate. The purpose of this work is to address this issue as clearly as possible by performing quantitative measurements on individual objects and on both type of waves, as far a comprehensive description of the global extinction process is intended. We show that the spatial modulation spectroscopy technique applied to a single nanoparticle is especially well suited in this context. This is illustrated by the model case of gold nanocubes supported either on a thin dielectric film or on a thick glass slide. Using the GOT in the particular case of a plane wave excitation at normal incidence, we were able to access the total extinction cross section of the supported scatterer. Moreover, we give evidence for the invariance of the extinction cross section relative to the transmitted wave, whether the nanoparticle is located in the front or behind the substrate with respect to the incoming beam. This effect can be seen as a manifestation of the optical reciprocity theorem with regard to this specific problem. We also discuss in which framework the experimental measurements can be pertinently reproduced by theoretical calculations, considering the setup geometry and the intrinsic optical response of the nanoparticle.

International audience; To be Raman-active (or, more generally, detectable using optical spectroscopy techniques), a vibrational mode of a nanosystem has to modulate its optical response. For small, isolated nanospheres, this is the case for only two categories of vibrational modes, namely, quadrupolar and radial ones. However, assembling nanospheres as dimers makes additional modes Raman-active, as previously demonstrated by the detection in the ultralow frequency range of a hybridized quasi-translation mode in previous measurements on single and ensembles of gold nanosphere dimers. In the present work, we use our recently developed single-particle Raman spectroscopy setup to compare inelastic light scattering by single isolated and dimerized gold nanospheres in an extended frequency range (0–40 GHz). The Raman spectra acquired on isolated nanoparticles present a single peak associated with their fundamental quadrupolar mode, consistently with previous ensemble measurements. In contrast, the spectra measured on dimers are richer and display a number of peaks increasing with decreasing interparticle distance, with all l = 2–8 Lamb modes detected in the quasi-contact case. These observations are rationalized using a recently developed classical model of inelastic light scattering by nanospheres. Importantly, our modeling approach takes into account the real electric field within the nanoparticles (computed using standard or generalized Mie theories) instead of relying on the frequently used Born and quasistatic approximations. This ingredient appears decisive for reaching a qualitative understanding of the measured spectra, explaining in particular the dominance of the l = 2 quadrupolar mode for isolated spheres and the increasing contribution of higher-order modes for increasing electromagnetic interactions in nanosphere dimers.

The detection rates of whole-body combined [18 F]NaF/[18 F]FDG positron emission tomography combined with computed tomography (PET/CT), CT alone, whole-body magnetic resonance imaging (WB-MRI), and X-ray were prospectively studied in patients with treatment-requiring plasma cell disorders The detection rates of imaging techniques were compared, and focal lesions were classified according to their anatomic location. Twenty-six out of 30 initially included patients were assessable. The number of focal lesions detected in newly diagnosed patients (n = 13) and in relapsed patients (n = 13) were 296 and 234, respectively. The detection rate of PET/CT was significantly higher than those of WB-MRI (P < 0.05) and CT (P < 0.0001) both in patients with newly diagnosed and in those with relapsed multiple myeloma (MM). The X-ray detection rate was significantly lower than those of all other techniques, while CT detected more lesions compared with WB-MRI at diagnosis (P = 0.025). With regard to the infiltration patters, relapsed patients presented more diffuse patterns, and more focal lesions located in the limbs compared with newly diagnosed patients. In conclusion, the detection rate of [18 F]NaF/[18 F]FDG PET/CT was significantly higher than those of CT, MRI, and X-ray, while the detection rate of X-rays was significantly lower than those of all other imaging techniques except for focal lesions located in the skull.

The low abundance of Hodgkin/Reed-Sternberg (HRS) cells in lymph node biopsies in classical Hodgkin lymphoma (cHL) complicates the analysis of somatic genetic alterations in HRS cells. As circulating cell-free DNA (cfDNA) contains circulating tumor DNA (ctDNA) from HRS cells, we prospectively collected cfDNA from 177 patients with newly diagnosed, mostly early-stage cHL in a monocentric study at Leuven, Belgium (n = 59) and the multicentric BREACH study by Lymphoma Study Association (n = 118). To catalog the patterns and frequencies of genomic copy number aberrations (CNAs), cfDNA was sequenced at low coverage (0.26×), and data were analyzed with ichorCNA to yield read depth-based copy number profiles and estimated clonal fractions in cfDNA. At diagnosis, the cfDNA concentration, estimated clonal fraction, and ctDNA concentration were significantly higher in cHL cases than controls. More than 90% of patients exhibited CNAs in cfDNA. The most frequent gains encompassed 2p16 (69%), 5p14 (50%), 12q13 (50%), 9p24 (50%), 5q (44%), 17q (43%), 2q (41%). Losses mostly affected 13q (57%), 6q25-q27 (55%), 4q35 (50%), 11q23 (44%), 8p21 (43%). In addition, we identified loss of 3p13-p26 and of 12q21-q24 and gain of 15q21-q26 as novel recurrent CNAs in cHL. At diagnosis, ctDNA concentration was associated with advanced disease, male sex, extensive nodal disease, elevated erythrocyte sedimentation rate, metabolic tumor volume, and HRS cell burden. CNAs and ctDNA rapidly diminished upon treatment initiation, and persistence of CNAs was associated with increased probability of relapse. This study endorses the development of ctDNA as gateway to the HRS genome and substrate for early disease response evaluation. ispartof: BLOOD ADVANCES vol:5 issue:7 pages:1991-2002 ispartof: location:United States status: published

This paper sheds light over the operations and internal structure of business angel groups (BAGs), a leading actor inside the informal venture capital industry, due to its capability to build cognitive resources and shared competencies that are eventually provided to funded ventures alongside equity capital. We develop a framework based on the role of business angels' decision-making style, human capital and motivation as major determinants of their active involvement in the many different activities performed by angel groups, either investment related activities or group management activities. Our empirical analysis relies on a novel survey-based dataset containing qualitative and quantitative information provided by the members of two large and rather homogeneous business angel groups located in France and in Italy. Results show that business angels with a control-oriented decision-making style tend to be more actively involved in key angel group activities. Human capital built through investment experience, retirement status, as well as initial motivation to join an angel group are also significant drivers of angel involvement in several key BAG activities.

PURPOSE: The prognosis of elderly patients with diffuse large B-cell lymphoma (DLBCL) is worse than that of young patients. An attenuated dose of chemotherapy—cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-miniCHOP)—is a good compromise between efficacy and safety in very elderly patients. In combination with R-CHOP (R2-CHOP), lenalidomide has an acceptable level of toxicity and may mitigate the negative prognosis of the non–germinal center B-cell–like phenotype. The Lymphoma Study association conducted a multicentric, phase III, open-label, randomized trial to compare R-miniCHOP and R2-miniCHOP. PATIENTS AND METHODS: Patients of age 80 years or older with untreated DLBCL were randomly assigned into the R-miniCHOP21 group or the R2-miniCHOP21 group for six cycles and stratified according to CD10 expression and age. The first cycle of rituximab was delivered by IV on D1 after a prephase and then delivered subcutaneously on D1 of cycles 2-6. Lenalidomide was delivered at a dose of 10 mg once daily on D1-D14 of each cycle. The primary end point was overall survival (OS). RESULTS: A total of 249 patients with new DLBCL were randomly assigned (127 R-miniCHOP and 122 R2-miniCHOP). The median age was 83 years (range, 80-96), and 55% of the patients were classified as non-GCB. The delivered dose for each R-miniCHOP compound was similar in both arms. Over a median follow-up of 25.1 months, the intention-to-treat analysis revealed that R2-miniCHOP did not improve OS (2-year OS 66% in R-miniCHOP and 65.7% in R2-miniCHOP arm, P = .98) in the overall population or in the non-GCB population. Grade 3-4 adverse events occurred in 53% of patients with R-miniCHOP and in 81% of patients with R2-miniCHOP. CONCLUSION: The addition of lenalidomide to R-miniCHOP does not improve OS. Rituximab delivered subcutaneously was safe in this population.

International audience; The present research sets out to reach a better understanding of the determinantsof business angels’ active involvement in making business angel groups accomplishdiverse functions and building cognitive resources and shared competencies. We developa framework where angels’ decision making style and professional experience are key inexplaining their degree and type of involvement with diverse business angel groupactivities. To test the related propositions, we conduct a questionnaire survey with themembers of one of the largest French business angel groups. Our results show thatbusiness angels with a control-oriented decision-making style, as well as angels withprevious professional experiences as a CEO and in marketing and sales, tend to be moreactively involved in key angel group activities, both with regard to investment relatedactivities and angel group management activities. While discussing the results, wepropose a tentative model of angel group cognition and outcomes for future extensions ofthe present research.; La présente recherche vise à mieux comprendre l’implication active des businessangels au sein des groupes de business angels, ainsi que la construction cognitive desressources et le partage des compétences. Nous développons un cadre conceptuel où lestyle de prise de décision des business angels et leur expérience professionnelle sont desclés pour expliquer leur degré et leur type d’implication parmi les diverses activités dugroupe de business angels. Afin de tester les propositions, nous avons mené une enquêtesous forme d’un questionnaire auprès d’un des plus grands groupes de business angelsfrançais. Nos résultats montrent que les business angels ayant un style de prise de décision« orienté-contrôle » ainsi que ceux ayant une expérience professionnelle en tant quedirecteur et en marketing et ventes sont plus impliqués dans les activités du groupe debusiness angels tant au niveau des activités d’investissement que des activités demanagement du groupe de business angels lui-même. Au titre des futures recherches quipourraient prolonger ce travail, nous proposons un modèle de groupe de business angels,en termes de cognition et de performance.

Nous expliquons la diffusion en France du mythe des 15 %, l’idée que les actionnaires attendent 15 % de ROE de leurs investissements. Nous montrons que l’existence d’une norme de 15 % de ROE est contraire à la théorie financière et à l’évidence empirique puis, par une analyse de la presse économique, comment le mythe des 15 % s’est diffusé dans les années 1990 sous l’influence de leaders d’opinion et avec le soutien de médias influents. Nous expliquons le succès de ce mythe par le contexte économique et institutionnel des années 1990, la présence d’un terreau favorable en France, et certains biais cognitifs. Nous contribuons à la compréhension des mythes financiers en développant un modèle d’analyse et en montrant que leur diffusion dépend de conditions historiques et culturelles spécifiques. We explain the diffusion and persistence of the 15 % myth in France, the idea that shareholders expect a 15 % ROE. We show that the existence of a 15 % ROE norm is not supported by financial theory nor by empirical evidence. By analyzing the economic press, we show how the 15 % myth has spread during the 1990’s under the influence of opinion leaders and with the support of major media. We explain the success of the 15 % myth by the economic and institutional context of the 1990’s, favorable cultural conditions in France and cognitive biases. We contribute to the understanding of financial myths by developing an analytical framework and by showing that their diffusion depends of specific historical and cultural conditions.

The French society of clinical biology "Biochemical markers of COVID-19" has set up a working group with the primary aim of reviewing, analyzing and monitoring the evolution of biological prescriptions according to the patient's care path and to look for markers of progression and severity of the disease. This study covers all public and private sectors of medical biology located in metropolitan and overseas France and also extends to the French-speaking world. This article presents the testimonies and data obtained for the "Overseas and French-speaking countries" sub-working group made up of 45 volunteer correspondents, located in 20 regions of the world. In view of the delayed spread of the SARS-CoV-2 virus, the overseas regions and the French-speaking regions have benefited from feedback from the first territories confronted with COVID-19. Thus, the entry of the virus or its spread in epidemic form could be avoided, thanks to the rapid closure of borders. The overseas territories depend very strongly on air and/or sea links with the metropolis or with the neighboring continent. The isolation of these countries is responsible for reagent supply difficulties and has necessitated emergency orders and the establishment of stocks lasting several months, in order to avoid shortages and maintain adequate patient care. In addition, in countries located in tropical or intertropical zones, the diagnosis of COVID-19 is complicated by the presence of various zoonoses (dengue, Zika, malaria, leptospirosis, etc.).

Background: Patients with cancer are more susceptible to infection because of immunosuppressive treatment given to cure cancer Several guidelines published at the beginning of the COVID-19 pandemic recommend delaying systemic anticancer treatment until complete resolution of COVID-19 symptoms In addition, it is important to segregate patients with cancer from patients with COVID-19 to avoid transmission Nevertheless, some patients will present both diseases, and the duration of eviction from cancer units and delay of cancer treatment after COVID-19 remains unclear Notably the duration of viral excretion after COVID-19 is a concern in immunosuppressed patients Methods: We tested all patients with a confirmed initial diagnosis of COVID-19 who needed to receive cancer or immunosuppressive treatment for a solid tumour, haematological or inflammatory disease in our centre from April 1st to May 15th 2020 We have repeated SARS-COV2 RT-PCR until negative viral shedding Results: We tested 49 consecutive patients: 53% had solid tumours, 37% haematological disease and 10% inflammatory disease 59% were under 65 years Overall, 82% of patients had a positive RT-PCR from day 14 to 20 after the initial diagnosis of COVID-19 infection, 60% from day 21 to 27 and 30% from day 28 to 34 Only 4/37 patients evaluated remained with a positive RT-PCR after day 35 No predictive factors were associated with a positive RT-PCR but our results suggest that patients treated for inflammatory disease had a shorter duration of positive RT-PCR 18 patients had their treatment delayed according to guideline recommendations and 17 patients received their treatment in a dedicated COVID-19 outpatient unit No symptomatic COVID-19 recurrence was observed during follow-up in patients who had received chemotherapy despite persistent positive RT-PCR Conclusions: We report here the first assessment of SARS-CoV2 RT-PCR kinetic in cancer patients A prolonged viral excretion is observed in patients treated for cancer A systematic retest is needed after day 14 if RT-PCR remains positive A specific unit dedicated to outpatients with persistent positive RT-PCR allows urgent anticancer treatment and avoids the risk of viral exposure for other immunodepressed patients Legal entity responsible for the study: The authors Funding: Has not received any funding Disclosure: All authors have declared no conflicts of interest

International audience; Tantôt associés aux festivités et aux célébrations, tantôt relevant du pathologique, l’alcool et ses usages apparaissent comme une évidence, un acte social faussement banal qui mérite pourtant d’être interrogé et analysé. Cet ouvrage collectif a justement vocation à mettre en lumière la singularité du regard des sciences sociales, mais aussi sa diversité, pour questionner cet objet aux facettes multiples et complexes mais relativement peu questionné dans ce cadre.Les neuf chapitres permettent tour à tour d’objectiver les politiques publiques à différentes échelles, mais aussi les trajectoires scientifiques de et autour de l’alcool ; de tordre des représentations, d’en suivre le fil historique, ou bien encore de rendre compte de pratiques de consommations. Subdivisé en trois axes, ce travail collectif investigue la manière dont l’alcool est traité – et partiellement façonné – par la science et le politique, questionne les usages de l’alcool et leurs significations, en particulier celles des populations largement médiatisées, et enfin offre comme perspective de décloisonner l’objet de ces espaces traditionnels en vue d’ouvrir de nouveaux espaces de recherche.Sommaire : IntroductionPenser l’alcool par les sciences sociales : un objet à tiroirsYannick Le Hénaff, Christophe Bonnet, François Feliu, Miléna SpachL’alcool, un objet politique et scientifiqueQuand l’alcoolisme est devenu une addiction : retour sur la construction d’une politique publique controverséeNicolas FortanéQui va gérer l’alcoolisation des jeunes lillois ? La régulation de la nuit festive comme transaction entre pouvoirs publics et acteurs privésCollectif CandelaÉvaluer la prévention du Syndrome d’Alcoolisation materno-Foetale (SAF)Louise Lartigot-HervierDes publics à la loupe : les jeunes et les femmesL’alcool et les jeunes, genèse télévisuelle d’un problème de santé publique (1978-1986)Sébastien Le PajolecLes régulations du boire adolescent au prisme du genre. Gestions parentales et juvéniles des contextes festifsNicolas Palierne et Ludovic GaussotGenre et alcool : quand les « filles aussi » s’enivrentMarie-Laure DéroffAux frontières de l’objet, des territoires à explorerAlcool et addiction dans le sport : des relations troublesCatherine PalmerLa nuit : verso du monde diurne, berceau des conduites d’excès. « Ethno-phénoménologie » des sorties juvénilesVéronique Nahoum-GrappeConclusionYannick Le Hénaff, Christophe Bonnet, François Feliu et Miléna Spach

Background: Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is a rare form of T-cell lymphoma arising adjacent to a breast implant, recently recognized as a provisional entity in the 2017 revised World Health Organization (WHO) lymphoma classification. The pathogenesis of this entity remains elusive even if gene alterations in epigenetic modifiers and JAK-STAT signaling are frequent. ECHELON 2 trial (Horwitz S et al. The Lancet 2019) has set BV-CHP as a new standard of treatment for CD30-positive peripheral T-cell lymphoma, mainly in systemic ALCL patients (pts) but not in BIA-ALCL. Our objective is to describe a series of pts with BIA-ALCL included in the LYSA registry focusing on the use of BV CHP as front-line chemotherapy for patient requiring chemotherapy. Methods: since 2016, a national multidisciplinary meeting has been implemented by the French Cancer Agency to better define therapeutic strategies for newly diagnosed cases after histologic confirmation. Meanwhile, BIA-ALCL registry was funded by the LYSA to collect ambispectively, in France and more recently in Belgium, patient clinical data including reasons for breast implantation, implant manufacturer, treatment and outcome. Results: from 2009 to 2021 , 85 pts (73 in France and 12 in Belgium) gave their informed consent to participate to the registry. Median age was 57 years (range 29-82) at diagnosis. In 39 out of 85 pts (45.9%) the first implant followed a mastectomy for breast cancer. In this analysis, only implants in the breast(s) where the lymphoma occurred have been considered. Five pts (5.9%) had bilateral lymphoma and 80 pts had unilateral lymphoma (35 left side and 45 right side), 35 pts were implanted once (41.2%), 35 twice (41.2%) and 15 pts (17.6%) 3 times or more. The median period between first implant and BIA-ALCL diagnosis was 12.2 years (range 4.1-40.5), and 7 years (range 0.2-25.4) from last implant to diagnosis. The clinical presentation was seroma in 64 pts (75.3%), breast tumor mass with or without seroma in 18 pts (21.1%) and 3 pts were diagnosed without any mass or seroma (1 contiguous lymph node involvement, 2 in the context of systematic implant removal). The two main clinical presentation (i.e. seroma and tumor mass) were most often correlated with the two distinct histological subtypes (in "situ/mixed" (n=62) or "infiltrative" (n=21)). For 2 pts, histological subtype was not available. The majority of pts were Ann Arbor stage I-II (n=65, 76.5%), and 18 (21.2%) pts were stage IV. Stage was unknown in 2 pts. Considering available information, almost all patients had at least one silicone-filled (n=76) and at least one textured implant (n=85) with Biocell texturation (n=61, 71.8%). No patient had only smooth implant. Implant removal with total capsulectomy was performed in 66 patients and 25 underwent chemotherapy based on CHOP or CHOP-like (4 to 6 cycles) chemotherapy regimens (n=13), BV-CHP (6 cycles) (n=10) and others (n=2). Among the patients receiving chemotherapy, CR was obtained in 21 pts (84%) and in 2 pts failed to respond (8%). Among the patients treated with BV-CHP, 8 pts achieved CR (80%) and 2 pts were not yet evaluated at the time of analysis. No limiting toxicity was noted. After a median follow-up of 28.6 months, 78 pts are alive and free of evolutive disease and 8 are lost to follow up. Seven pts died, either from lymphoma progression alone (n=2) or associated with concomitant active breast cancer (n=2), one from breast cancer alone, one from lung epidermoid cancer and one due to myocardial infarction. Patients with an "infiltrative" histological subtype have a significantly worse outcome with a 2y-PFS of 73.8% vs 96.7% for other subtypes ("in situ/mixed subtypes") (p=0.0039, HR=5.3) and a 2y-OS of 78.7% vs 100% (p=0.0022, HR=8.5). With a median follow-up of one year, the 10 patients treated with BV-CHP are alive and free of evolutive disease at the time of analysis. Conclusions: We report on the basis of a limited series of patients that 6 cycles of BV-CHP provide an excellent disease control in patients with BIA-ALCL requiring chemotherapy. Confirmation of these results on a larger series of patients with a longer follow-up is needed. Such observation provides basis for a prospective trial in order to determine if treatment with BV-CHP could be installed as a standard of care for higher risk patients with BIA-ALCL, as those presenting with tumor mass and /or infiltrative subtype. Disclosures Le Bras: Novartis: Honoraria; Celgene BMS: Research Funding; Takeda: Honoraria, Research Funding; Kite Gilead: Honoraria. Bachy: Kite, a Gilead Company: Honoraria; Novartis: Honoraria; Daiishi: Research Funding; Roche: Consultancy; Takeda: Consultancy; Incyte: Consultancy. Bonnet: Roche: Consultancy. André: AbbVie: Other: Travel/accomodation/expenses; Roche: Other: Travel/accomodation/expenses, Research Funding; Johnson & Johnson: Research Funding; Celgene: Other: Travel/accomodation/expenses; Bristol-Myers-Squibb: Consultancy, Other: Travel/Accommodations/Expenses; Karyopharm: Consultancy; Gilead: Consultancy, Other: Travel/Accommodations/Expenses; Incyte: Consultancy; Takeda: Consultancy, Research Funding. Haioun: Amgen: Honoraria, Research Funding; Servier: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Miltenyi: Honoraria, Research Funding.

Introduction: Older classical Hodgkin lymphoma (cHL) patients are characterized by a significant reduced survival as compared to younger patients. In relapsed and refractory HL, prospective and retrospective studies showed that bendamustine monotherapy provided interesting efficacy with 30% of complete response with an acceptable toxicity profile. We developed the PVAB (Prednisone, Vinblastine, Doxorubicin, Bendamustine) regimen in first line therapy to improve prognosis of older HL with advanced stage. Methods: In this prospective phase II, we recruited newly diagnosed classical HL patients age of 61 years or older with an advanced stage (Ann Arbor stage III, IV, IIB with risk factors). Inclusion criteria were: ECOG performance status 0-2; adequate cardio-pulmonary function with LVEF ≥ 50%; adequate renal function with creatinine clearance ≥ 40 mL/min; HIV negative; For patients aged 70 years old and more, a Mini Nutritional Assessment (MNA) ≥ 17. Treatment consisted of 6 cycles of prednisone (40mg/m 2 D1-5), vinblastine (6mg/m 2, D1), doxorubicin (40mg/m 2, D1) and bendamustine (120mg/m 2, D1) every 21 days. The primary endpoint was the complete metabolic response (CMR) rate according to local review after 6 cycles of study treatment or at premature treatment discontinuation according to Lugano Classification. We presented the final analysis of the study with a median follow-up of 42 months (range, 0.5-63.8), with prognostic analyses for progression free survival (PFS) measured from the date of inclusion to the date of progression, relapse or death from any cause. Prognostic factors included baseline clinical and biological characteristics, geriatric assessments and 18F-FDG PET/CT metabolic parameters especially baseline total metabolic tumor volume (TMTV). Optimal thresholds for some parameters were calculated using X-Tile approach. Results: Between July 2015 and July 2018, 89 patients were included in 34 LYSA centers. The median age was 68 years (range, 61-88) with 35 patients ≥70 years old (39%). The main histological subtype was nodular sclerosis cHL (n=56, 63%) with 26 EBV associated cases (LMP1 staining). Ann Arbor stages were as follows: II (n=3, 3%), III (n=30, 34%), IV (n=56, 63%). B symptoms were present in 57% of patients; 70 patients (80%) had IPS≥3. The median of CIRS-G score was 3 (range, 0-12). Seventy-eight patients (88%) completed the 6 cycles of PVAB. Update results for toxicity showed that 28 patients (32%) presented at least one serious adverse event (SAE) in particular infections (n=13, 15%), blood (n=11, 12%) and cardiac disorders (n=4, 4.5%). The CMR rate according to local review corresponding to the primary endpoint of the study was 77.5% (95%CI, 67-86) with 69 patients in CMR. After central review of 79 available PET/CT images, the CMR rate was 78.5%. Thirty-one patients relapsed or progressed (35%). The 4-year PFS rate was 50% (95%CI, 39-61). For the 69 patients achieving CMR, the 4-year disease free survival (DFS) rate was 62.8% (95%CI, 49-74). Twenty-four patients (27%) died: 11 cHL (46%), 4 treatment toxicity (17%), 6 second cancers (25%), 3 other causes after treatment (infection, cardiac insufficiency, pulmonary embolism, 12%). The 4-year overall survival rate was 69% (95%CI, 57-79). In univariate analysis, altered ECOG PS, Ann Arbor stage IV, bulky disease (>7cm), B-symptoms, extra-nodal involvement (>1), bone or medullar involvement, liver involvement, albumin (≤30g/l), hemoglobin level (88mg/l), TMTV (>450ml) and number of medications non-related to HL (>5) were associated with PFS. In multivariate analysis, liver involvement (HR: 3.79; 95%CI,1.71-8.43; P=0.001), lymphopenia (HR: 3.04; 95%CI,1.54-6.01; P=0.001), CRP (HR: 3.37; 95%CI, 1.69-6.69; P=0.0005) and co-medications (HR: 2.85; 95%CI,1.44-5.66; P=0.003) were independently associated with PFS. Conclusions: PVAB regimen provided high CMR (77.5%) with acceptable toxicity for advanced stage cHL patient over 60 years. The 4-year PFS and OS rates were 50% and 69% respectively, these survival endpoints were influenced by not related-lymphoma events. Prognostic analyses showed that specific involved site (liver), biological parameters (lymphocyte count and CRP) and patient's comorbidity (co-medications) influenced independently PFS. Disclosures Ghesquieres: Celgene: Consultancy, Honoraria, Other: Travel, accommodation, expenses; Roche: Consultancy, Honoraria, Other: Travel, accommodation, expenses; Gilead Sciences: Consultancy, Honoraria, Other: Travel, accommodation, expenses; Mundipharma Research Limited: Consultancy, Honoraria; Takeda: Other: Travel, accommodation, expenses. Casasnovas: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Jaccard: Janssen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Abbvie: Honoraria. Laribi: Jansen: Research Funding; Novartis: Other: Personal Fees, Research Funding; Takeda: Other: Personal Fees, Research Funding; AbbVie: Other: Personal Fees, Research Funding; IQONE: Other: Personal Fees; Astellas Phama, Inc.: Other: Personal Fees; BeiGene: Other: Personal Fees; AstraZeneca: Other: Personal Fees; Le Mans Hospital: Research Funding. Morschhauser: BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy; Incyte: Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; Genmab: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZenenca: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Speakers Bureau; Janssen: Honoraria; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Brice: Takeda: Consultancy, Honoraria, Research Funding; BMS: Honoraria; MSD: Honoraria. OffLabel Disclosure: Bendamustine is off-label drug use in Hodgkin lymphoma

Methods : This multicentric retrospective study aimed to evaluate the efficacy and the safety of the combination of BBV in patients with non-cutaneous R/R PTCL among 21 LYSA centers in France and Belgium. The primary objective was to evaluate the best overall response rate (ORR) (complete response (CR) and partial response (PR)). Secondary objectives were progression free survival (PFS), overall survival (OS), duration of response (DoR), impact of transplantation on outcome, and safety. Patients treated between January 2013 and October 2020 were reviewed and all the data were collected through an electronic questionnaire sent to all the physicians. Results : Eighty two patients with R/R PTCL (40 angioimmunoblastic lymphoma (AITL), 2 T-cell lymphoma with TFH phenotype ,13 PTCL not otherwise specified (PTCL NOS), 5 Alk+ anaplastic large cell lymphoma (ALCL), 17 Alk- ALCL, , 1 Extranodal NK-/T-cell lymphoma, 3 Enteropathy-associated T-cell lymphoma (EATL), 1 subcutaneous panniculitis) were included. Median age at beginning of BBV was 60 years, most of patients were male (61%), had advanced stage (88%) and an IPI ≥ 2 (79%). Half of patients were refractory to their last treatment. Median number of prior regimens was 1 (range 1 to 6). The best ORR was 71%, with 51% of patients in CR. In multivariable analysis, only the relapse status after the last regimen (relapse vs refractory) was associated with ORR, relapsed patients having a better ORR (83% vs 57% in refractory patients, p=.014, OR=3.70 (95%CI:1.3-10.5)). Median DoR was 15.4 months in patients with CR but differed significantly whether patients were transplanted or not (Not reached vs 8.4 months, p=.0055). Twenty-two patients (30% of patients ≤ 70 years of age) were transplanted (6 autologous and 16 allogenic). With a median follow-up of 9 months, the median PFS and OS were 8.3 and 26.3 months respectively. In multivariable analysis, only 2 factors had a significant impact on PFS and OS: best response (CR/PR vs SD/PD with a median PFS of 17.4 vs 1.9 months, p Fifty-nine percent of patients experienced a grade 3 to 4 adverse event which was mainly hematologic toxicity. Treatment had to be stopped in 11% of patients. Conclusion: To the best of our knowledge, this is the first study reporting on the combination of BBV in the treatment of R/R PTCL in such a large cohort. The results are very encouraging with a high response rate, long DoR in responding patients and a very good outcome. Furthermore, patients in CR who are eligible for transplant have the best outcome, making this combination a good candidate as salvage therapy before transplant consolidation in these high-risk lymphomas with limited treatment options. Figure 1 Figure 1. Disclosures Bouabdallah: Kite/Gilead: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria. Herbaux: Takeda: Honoraria, Research Funding; Janssen: Honoraria; Roche: Honoraria; Abbvie: Honoraria, Research Funding. Brice: MSD: Research Funding; Amgen: Other: Travel/accommodations/expenses; Roche: Other: Travel/accommodations/expenses; Takeda: Research Funding. Sibon: Abbvie: Consultancy; Janssen: Consultancy; Roche: Consultancy; iQone: Consultancy; Takeda: Consultancy. Laribi: AstraZeneca: Other: Personal Fees; AbbVie: Other: Personal Fees, Research Funding; IQONE: Other: Personal Fees; Astellas Phama, Inc.: Other: Personal Fees; BeiGene: Other: Personal Fees; Takeda: Other: Personal Fees, Research Funding; Novartis: Other: Personal Fees, Research Funding; Le Mans Hospital: Research Funding; Jansen: Research Funding. Damaj: roche: Consultancy, Honoraria; takeda: Consultancy, Honoraria. OffLabel Disclosure: Brentuximab Vedotin and Bendamustine

A thermodynamic study was undertaken on two kinds of NaCrO2(s) powder, a commercial and an experimental one synthetized. Heat capacity measurements were carried out in the temperature range of 25–600 °C using a differential scanning calorimeter. Gibbs energy of formation versus temperature was deduced using these experimental data, the enthalpy of formation from literature and the entropy at room temperature deduced from ab initio calculations combining with a quasi-harmonic statistical model. The equation obtained is given by: ΔfG°(T) (NaCrO2) (kJ/mol O2)=−876.094+0.191xT (±2%). The temperature of phase transition measured by differential thermal analysis at (819 ± 4) °C is slightly higher than the temperature in the literature attributed to the decomposition of NaCrO2 into Cr2O3 and Na2O. However, the X-ray diffraction patterns showed only NaCrO2 phase which didn’t confirm the decomposition reaction.

Background. Muscle depletion (MD) assessed by computed tomography (CT) has been shown to be a predictive marker in solid tumors, but has not been assessed in non-Hodgkin’s lymphomas. Despite software improvements, MD measurement remains highly time-consuming and cannot be used in clinical practice. Methods. This study reports the development of a Deep-Learning automatic segmentation algorithm (DLASA) to measure MD, and investigate its predictive value in a cohort of 656 diffuse large B cell lymphoma (DLBCL) patients included in the GAINED phase III prospective trial (NCT01659099). Results. After training on a series of 190 patients, the DLASA achieved a Dice coefficient of 0.97 ± 0.03. In the cohort, the median skeletal muscle index was 50.2 cm2/m2 and median muscle attenuation (MA) was 36.1 Hounsfield units (HU). No impact of sarcopenia was found on either progression free survival (PFS) or overall survival (OS). Muscular hypodensity, defined as MA below the tenth percentile according to sex, was associated with a lower OS and PFS, respectively (HR = 2.80 (95% CI 1.58–4.95), p &lt, 0.001, and HR = 2.22 (95% CI 1.43–3.45), p &lt, 0.001). Muscular hypodensity appears to be an independent risk factor for mortality in DLBCL and because of DLASA can be estimated in routine practice.

Introduction: Primary mediastinal B cell lymphoma (PMBL) is clinically and biologically distinct from the other subtypes of diffuse large B cell lymphoma (DLBCL), typically affecting young female patients (pts) with a bulky mediastinal mass. Standard treatment (TRT) is a combination of anti-CD20 antibody (Ab) and anthracycline-based chemotherapy. We aimed to compare patients' outcomes after CHOP delivered every 21 days (CHOP21) or 14 days (CHOP14) or ACVBP combined with anti-CD20 Ab in real life. Methods: All Pts treated in LYSA centers were eligible in this retrospective analysis. Inclusion criteria were as follow: age ≥18 years (yrs), newly diagnosed PMBL, TRT with CHOP or ACVBP plus anti-CD20 Ab between 2006 and 2017, and patient non-opposition statement. Primary endpoint was progression-free survival (PFS), secondary endpoints were: overall survival (OS), response rate (Lugano 2014) and total metabolic tumor volume (TMTV). Results: 313 pts were enrolled from 25 LYSA centers in France and Belgium. In all, median age at diagnosis was 32 (18-88) yrs. Majority of pts were female pts (60.7%) and presented at diagnosis with a good performance status (0-1: 81.8%), stage I-II (57.5%), elevated LDH (85%), Bulk>10cm (58.5%) and low/low-intermediate aaIPI 0-1 (56.7%). Pts in the CHOP21 (n=57) group were older (median 40 yrs, vs 33 vs 29.5, p Complete metabolic response rates at end of TRT were comparable between CHOP21, CHOP14 and ACVBP groups: 81.1%, 90.9%, and 85.5%, respectively (p=0.46). 37 (11.8%) pts progressed including 32 (10.2%) who displayed primary refractory disease and 6 (16.2%) pts who relapsed after consolidation ASCT. CNS relapse occurred in 9 (2.9%) pts. Median time between ASCT and relapse was 3 (2-58) months. Patients received the following salvage TRTs: high dose chemotherapy (HDC: R-ICE/R-DHAOX-like) (n=30) followed by second-line consolidation ASCT (n=11/30) and post-ASCT mediastinal RT (n=5/11); salvage RT without chemotherapy (n=1); other regimens (R-CHOP, R-GEMOX) (n=3); none (n=3). 2-yrs second PFS (PFS2) rates in pts who had previously received CHOP21, CHOP14 and ACVBP were: 20.5% vs 62.5% vs 18.8% (p=0.43). Only HDC + ASCT strategy granted disease control (2-yrs PFS2: 32.3%). Median follow up was 44 (1-153) months and the CHOP21, CHOP14, ACVBP 5-yrs PFS and 5-yrs OS were: 74.7% (95%CI: 64-97.1%), 89.4% (82.7-96.6%), 89.4% (84.8-94.2%) (p=0.018, Figure A); and 81% (70-94.4%), 100% (100-100%), 92.4% (88.4-96.7%) (p=0.0036, Figure B), respectively. In a multivariate model including TRT group, consolidation ASCT and/or RT, aaIPI, Bulk>10cm and TMTV≥360cm3, CHOP14 was not associated with better PFS as compared to ACVBP and CHOP21 (p=0.1548). Baseline higher TMTV (≥ 360 cm3) was associated with lower PFS in multivariate analysis, independently of TRT (HR=0.41 [0.2-0.85], p=0.02). All grades TRT-related adverse events were similar between the groups, except for an excess of febrile neutropenia (5.3% vs 5.3% vs 24.4%, p Conclusion These results confirm the favorable outcome of PMBL pts treated with CHOP14 and ACVBP plus anti CD20 Ab. The toxicity of ACVBP was more pronounced and CHOP14 was associated with a better OS. Baseline TMTV≥360cm3 is a highly predictive factor of unfavorable outcome in PMBL pts, independently of TRT. We recommend R-CHOP14 as standard of care in PMBL. Figure Disclosures Camus: ROCHE: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); PFIZER: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); AMGEN: Honoraria; JANSSEN: Honoraria. Decazes:Bayer: Other: travel, accomodations, expenses. Bernard:Janssen: Other: Travel and accommodation . Gandhi Laurent:Abbevie, Pfizer, Takeda, Roche: Other: Travel; Roche, Takeda, Iqone, Accord: Consultancy; Roche, Takeda, Accord: Honoraria. Laribi:amgen: Research Funding; novartis: Honoraria, Research Funding; takeda: Research Funding; abbvie: Honoraria, Research Funding. Houot:Gilead: Honoraria; Kite: Honoraria; Roche: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; MSD: Honoraria. Tilly:BMS: Honoraria.

International audience

International audience

International audience; Lenalidomide is a potent immunomodulatory agent that has demonstrated clinical activity in the treatment of both diffuse large B cell lymphomas (DLBCL) and mantle cell lymphomas (MCL). In relapsed/refractory (R/R) DLBCL, two large prospective studies evaluating lenalidomide monotherapy demonstrated an overall response rate (ORR) of 28% (N = 108) and 27.5% (N = 51), respectively [1, 2]. In patients with R/R MCL patients, lenalidomide induced an ORR of 40% (N = 170) [3, 4]. In 2013, the FDA approved lenalidomide for the treatment of R/R MCL. Obinutuzumab is a unique type II glycoengineered monoclonal anti-CD20 antibody (Ab) with increased ADCC and increased direct cell death induction compared to rituximab. In monotherapy, obinutuzumab demonstrated efficacy in patients with MCL and DLBCL [5]. The ORR after treatment with obinutuzumab monotherapy was 28% and 27% in R/R DLBCL and MCL, respectively [5]. Furthermore, the combination of lenalidomide and rituximab (R 2 regimen) demonstrated promising efficacy in patients with follicular lymphoma (FL) [6, 7], MCL [8, 9], and DLBCL [10-13]. We hypothesized that the combination of obinutuzumab (GA) with lenalidomide (LEN) might be even more efficient while retaining a good safety profile. In a phase I B study, we previously identified 20 mg/day as the recommended dose (RD) of lenalidomide in * Franck Morschhauser

TPS7568 Background: Most patients with the indolent non-Hodgkin lymphoma (NHL) subtypes FL or MZL respond to first-line treatment but relapse is common, and there is no single standard treatment for patients with R/R FL or MZL. Tafasitamab is an Fc-engineered humanized monoclonal antibody (mAb) against CD19 which is broadly expressed in FL and MZL, and regulates B-cell proliferation via B-cell receptor signaling. In preclinical studies, tafasitamab has shown activity against NHL cell lines in combination with rituximab (anti-CD20 mAb) and lenalidomide (LEN). Tafasitamab monotherapy has shown promising clinical activity in a phase 2a study in patients with R/R NHL (NCT01685008), with an ORR of 29% (n/N = 10/34) in patients with FL and 33% (n/N = 3/9) in patients with MZL. In an ongoing phase 2, single-arm study (L-MIND, NCT02399085), tafasitamab plus LEN followed by tafasitamab alone demonstrated an ORR of 57.5% (n/N = 46/80) in patients with R/R diffuse large B-cell lymphoma (FDA approved indication). These preclinical and clinical observations from phase 2 trials suggest a potential clinical benefit of tafasitamab plus LEN and rituximab for patients with R/R FL or MZL. Methods: This phase 3 double-blind, placebo-controlled, randomized study is designed to investigate whether tafasitamab plus LEN and rituximab provides improved clinical benefit compared with LEN and rituximab in patients with R/R FL or R/R MZL. Patients will be randomized 1:1 to receive tafasitamab (12 mg/kg IV on days 1, 8, 15, and 22 of a 28-day cycle [cycles 1–3], then days 1 and 15 [cycles 4–12]) plus LEN (20 mg PO QD, days 1–21/ cycle for 12 cycles) and rituximab (375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1, then day 1 of cycles 2–5), or placebo (0.9% saline solution IV) plus LEN and rituximab. The primary study endpoint is PFS (investigator assessed [INV] by Lugano 2014 criteria) for patients with FL. Key secondary endpoints are PFS (INV) in overall population (FL and MZL), PET-CR rate (INV) at end of treatment (4–8 weeks after last treatment) and OS in patients with FL. Inclusion criteria include age ≥18 y, histologically confirmed FL (grade 1, 2, or 3a) or MZL (nodal, splenic, or extranodal), documented R/R disease, ≥1 prior systemic anti-CD20 therapy (including anti-CD20 refractory disease), ECOG PS ≤2, adequate systemic organ function, and high tumor burden (per GELF criteria). Exclusion criteria include prior rituximab plus LEN treatment, history of radiotherapy for other diseases (≥25% of bone marrow), nonhematologic malignancy, congestive heart failure (LVEF < 50%), active systemic infection, known CNS lymphoma, or severe immunocompromised state. inMIND (NCT04680052, EudraCT2020-004407-13) is currently enrolling patients; planned enrollment is 528 patients with R/R FL and 60–90 patients with R/R MZL. Clinical trial information: NCT04680052.

The detection rates of whole-body combined [

The acoustic vibrations of single monomers and dimers of gold nanoparticles were investigated by measuring for the first time their ultralow-frequency micro-Raman scattering. This experiment provides access not only to the frequency of the detected vibrational modes but also to their damping rate, which is obscured by inhomogeneous effects in measurements on ensembles of nano-objects. This allows a detailed analysis of the mechanical coupling occurring between two close nanoparticles (mediated by the polymer surrounding them) in the dimer case. Such coupling induces the hybridization of the vibrational modes of each nanoparticle, leading to the appearance in the Raman spectra of two ultralow-frequency modes corresponding to the out-of-phase longitudinal and transverse (with respect to the dimer axis) quasi-translations of the nanoparticles. Additionally, it is also shown to shift the frequency of the quadrupolar modes of the nanoparticles. Experimental results are interpreted using finite-element simulations, which enable the unambiguous identification of the detected modes and despite the simplifications made lead to a reasonable reproduction of their measured frequencies and quality factors. The demonstrated feasibility of low-frequency Raman scattering experiments on single nano-objects opens up new possibilities to improve the understanding of nanoscale vibrations with this technique being complementary with single nano-object time-resolved spectroscopy as it gives access to different vibrational modes.