Clémentine Sarkozy

• Hospices Civils de Lyon (Centre Hospitalier Universitaire de Lyon)

In mantle cell lymphoma, early progression of disease has been associated with short overall survival. The impact of clinical, pathological, and treatment strategies on the risk of early relapse has not been assessed in a large cohort of patients. We performed a pooled analysis of patients recruited in France from six randomized first-line MCL tria...

The tissue architecture of classic Hodgkin Lymphoma (CHL) is ｕｎｉｑｕｅ among cancers and characterized by rare malignant Hodgkin and Reed-Sternberg cells that co-evolve with a complex ecosystem of immune cells in the tumor microenvironment (TME). The lack of a comprehensive systems-level interrogation has hindered the description of disease heterogene...

Background In the phase I Epi-RCHOP study (NCT02889523), we reported that R-CHOP-tazemetostat was well tolerated with the recommended phase II dose, consistent with monotherapy. Methods Phase II included newly diagnosed diffuse large B cell lymphoma patients aged 60–80 years who received six cycles of rituximab-CHOP (R-CHOP) with continuous tazeme...

Burkitt lymphoma is a rare lymphoma entity that represents less than 5% of adult lymphomas. Although prognosis has improved with dose-dense therapy, Burkitt lymphoma remains an area of clinical and biological research with specificities due to the high incidence of CNS involvement and tumour lysis syndrome in patients with a high tumour burden. Few...

Introduction Despite therapeutic advances, optimal management of mantle cell lymphoma (MCL) in young high risk patients remains an unmet need. Progression within 24 months of starting chemotherapy (POD24) indicates poor prognosis but can't guide initial therapy. TP53 mutations (Eskelund 2017) and CDKN2A deletions (del) (Delfau-Larue 2015, Le Bris 2...

PURPOSE Minimal residual disease (MRD) can predict outcomes in patients with mantle cell lymphoma (MCL) but data are limited for younger patients undergoing ASCT (autologous-stem-cell-transplantation) and rituximab maintenance (RM) and no data are available on the clinical value of combining MRD with positron-emission-tomography (PET). PATIENTS AND...

Introduction: Since 2020, Chimeric antigen receptor T-cell (CAR-T), namely Brexucabtagene autoleucel (Brexu-Cel), is approved for mantle cell lymphoma (MCL) patients in relapsed or refractory (RR) post BTK inhibitors (BTKi), based on significant complete and duration of response (DOR) in ZUMA-2 trial (Wang et al, NEJM, 2020). Real-life studies conf...

Follicular lymphoma (FL) is the second most common type of lymphoma (20% of all non‐Hodgkin lymphomas), derived from germinal centre (GC) B cells, and is characterised by its significant clinical, prognostic and biological heterogeneity, leading to complexity in management. Despite significant biological investigation and indisputable clinical prog...

Objectives: The Robust and Optimized Biomarker Identifier (ROBI) feature selection pipeline is introduced to improve the identification of informative biomarkers coding information not already captured by existing features. It aims to accurately maximize the number of discoveries while minimizing and estimating the number of false positives (FP) wi...

Obinutuzumab (O) and Rituximab (R) are two CD antibodies that have never been compared in a prospective randomised trial in mantle cell lymphoma (MCL). Herein, we report the long-term outcome of the LYMA-101 (NCT02896582) trial, in which newly diagnosed MCL patients were treated with chemotherapy plus O before transplantation followed by O maintena...

In this retrospective study, CAR T-cells remained effective in relapsed/refractory LBCL patients after prior exposure to bispecific antibodies (BsAbs) targeting different antigens. These results are relevant to clinical practice, particularly given the increasing use of BsAbs in earlier treatment lines.

Mantle cell lymphoma (MCL) is a rare (5-7%), aggressive B-cell non-Hodgkin's lymphoma with well-defined hallmarks (e.g. Cyclin D1, SOX11), and whose expansion is highly dependent on the tumor microenvironment (TME). Parallel drastic progresses in the understanding of the lymphomagenesis and improved treatments led to paradigm shift in this B-cell m...

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO o...

Between 2011 and 2012, a phase II trial evaluated the use of the RiBVD (Rituximab, Bendamustine, Velcade and Dexamethasone) combination as first-line treatment for mantle cell lymphoma (MCL) patients aged over 65. We have now re-examined the classic prognostic factors, adding an assessment of the mutation status of TP53. Patients (n=74; median age...

Follicular lymphoma is the most common indolent lymphoma accounting for approximately 20%-25% of all new non-Hodgkin lymphoma diagnoses in western countries. Whilst outcomes are mostly favorable, the spectrum of clinical phenotypes includes high-risk groups with significantly inferior outcomes. This review discusses recent updates in risk stratific...

TPS7590 Background: Inhibition of Bruton tyrosine kinase (BTK) has emerged as a strategy for treatment of patients (pts) with B-cell malignancies including indolent non-Hodgkin lymphomas. Zanubrutinib is a second-generation, potent, and specific BTK inhibitor and has shown to be more effective and better tolerated than first-generation BTK inhibito...

7508 Background: The phase III LYMA trial demonstrated the efficacy (OS, PFS, EFS) and safety of rituximab maintenance (RM) post autologous stem cell transplant (ASCT) in first line for young patients with mantle cell lymphoma (MCL) (Le Gouill et al, NEJM). Herein, we present the first long-term analysis of the LYMA trial. Methods: 299 patients wer...

Purpose: High-risk clonal hematopoiesis (CH) is frequently incidentally found in patients with solid tumors undergoing plasma cell-free DNA sequencing. Here, we aimed to determine if the incidental detection of high-risk CH by liquid biopsy may reveal occult hematologic malignancies in patients with solid tumors. Materials and methods: Adult pat...

Advances in molecular profiling of newly diagnosed diffuse large B‐cell lymphoma (DLBCL) have recently refine genetic subgroups. Genetic subgroups remain undetermined at the time of relapse or refractory (RR) disease. This study aims to decipher genetic subgroups and search for prognostic molecular biomarkers in patients with RR‐DLBCL. From 2015 to...

Follicular lymphoma (FL) is the most common indolent form of non-Hodgkin lymphoma. Histological transformation of FL to a more aggressive form of lymphoma occurs with a linear incidence of 2-3% per year and is associated with poor outcome. Divergent clonal evolution and an altered tumour microenvironment (TME) have both been implicated in the trans...

Follicular lymphoma (FL) is an indolent cancer of mature B-cells but with ongoing risk of transformation to more aggressive histology over time. Recurrent mutations associated with transformation have been identified; however, prognostic features that can be discerned at diagnosis could be clinically useful. We present here comprehensive profiling...

Introduction: Histological transformation from follicular lymphoma (FL) to aggressive B-cell lymphoma (tFL) is a disease course altering event linked to poor prognosis for affected patients. From a biological point of view, it is paradigmatic of disease dynamics with distinct clinical stages that project onto genetically and phenotypically divergen...

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) char- acterized by the translocation t(11;14) (q13;q32) and a poor response to rituximab–anthracycline-based chemotherapy. High-dose cytarabine-based regimens offer a durable response, but an important number of MCL patients are not eligible for intensive treatment and ar...

We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the re...

Background: Intravascular large B-cell lymphoma (lVLBCL) is a very rare type of large B-cell lymphoma. Methods: We conducted a retrospective study on IVLBCL patients treated from 2000 to 2016 in LYSA cooperative group centers. Results: Sixty-five patients were identified in 23 centers. Median age at diagnosis was 69 years (range 23-92). Thirty...

Background: Diffuse large B cell lymphoma (DLBCL) is an aggressive malignancy of mature B cells. The disease has traditionally been subdivided into cell-of-origin (COO) subtypes - germinal centre B cell-like (GCB) or activated B cell-like (ABC) - as determined by expression profiling or immunohistochemistry of the tumor cells. However the role of t...

Follicular lymphoma (FL) is an indolent lymphoma of mature B-cells but may transform to a more aggressive histology, most commonly diffuse large B cell lymphoma. Recurrent mutations associated with transformation have been identified; however, biological predictors to guide initial therapy have remained elusive. We hypothesized that clonal heteroge...

Background Primary refractory (PREF) follicular lymphoma (FL) has a completely different clinical course from that of FL that responds to front-line treatments. In addition to having poor responses to salvage therapies, it seems that patients with PREF are at increased risk of histological transformation (HT). The Aristotle consortium presented the...

Background T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory domains (TIGIT), and costimulatory receptor CD226 competitively bind 2 ligands, CD155 and CD112, which are expressed by tumor cells and antigen-presenting cells in the tumor microenvironment. 1 2 Dual TIGIT/programmed cell death protein-1 (PD-1) blocka...

In this retrospective study, we report 70 cases of Epstein-Barr virus (EBV)+ diffuse large B-cell lymphoma not otherwise specified (DLBCL-NOS) among 1696 DLBCL-NOS cases diagnosed between 2006 and 2019 (prevalence of 4.1%). At diagnosis, median age was 68.5 years; 79% of the cases presented with an advanced-stage disease (III-IV), 48% with extranod...

Introduction Primary Mediastinal Large B-Cell Lymphoma (PMBL) is a rare subtype of lymphoma, clinically and biologically distinct from diffuse large B-Cell Lymphoma (DLBCL) that shows overlapping features with classical Hodgkin Lymphoma (cHL). If first line strategies lead to 80-85% of curability, relapse occurs early with a chemo-refractory diseas...

Classical Hodgkin lymphoma is a neoplastic hematological disease. Standard first-line therapy, including chemotherapy and radiotherapy, is curative in >85% of early-stage patients, with a 5-year survival rate of >95%. However, approximately 15% of patients have hard-to-treat lymphoma with poor outcomes, and new treatment strategies are needed for t...

Aim: Anti-CD20 monoclonal antibody is a cornerstone therapy for follicular lymphoma. Following anti-CD20 therapy, a potential decrease in CD20 antigen, and therefore a loss of the tumor target might be expected. However, the incidence and clinical significance of CD20 loss on tumor cells in patients with relapsed or refractory follicular lymphoma a...

Primary mediastinal large B-cell lymphoma (PMBL) is a type of aggressive B-cell lymphoma that typically affects young adults, characterized by presence of a bulky anterior mediastinal mass. Lymphomas with gene expression features of PMBL have been described in non-mediastinal sites, raising questions about how these tumors should be classified. Her...

Background. Diffuse large B cell lymphoma (DLBCL) is the most common adult non-Hodgkin lymphoma. Despite therapeutic advances, 40% of the patients (pts) and especially pts older than 65 years old (y/o), will experience a relapsed or refractory (R/R) disease. Novel therapies as well as predictive biomarkers are required for these patients with a poo...

Background: Early drug development is associated with a high rate of failure in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBLC), partly due to genomic heterogeneity. Precision medicine aims at identifying patients with cancer who are likely to respond to targeted therapies. Here we assessed the clinical impact of char...

The mutational landscape of grey zone lymphoma (GZL) has not yet been established and differences to related entities are largely unknown. Here, we studied coding sequence mutations of 50 EBV-negative GZL and 20 polymorphic EBV-positive DLBCL NOS (poly-EBV-L) in comparison to classical Hodgkin lymphoma (cHL), primary mediastinal large B cell lympho...

Mantle cell lymphoma has a dismal prognosis at relapse or in the refractory setting. Among therapies, mTor pathway targeting by temsirolimus has been the first strategy approved for relapse in Europe. While its efficacy in monotherapy has long been demonstrated, its use remains limited. In the T3 phase Ib clinical trial, we investigated the recomme...

Gray zone lymphoma (GZL), a B-cell lymphoma with features intermediate between large B-cell lymphoma (LBCL) and classic Hodgkin lymphoma (cHL), is a rare and poorly defined entity. Alongside GZL, a subset of Epstein-Barr virus (EBV)–positive diffuse large B-cell lymphoma (DLBCL) has been described with polymorphic/GZL-like morphology (polymorphic-E...

Introduction: Mantle cell lymphoma (MCL) is an aggressive B cell non-Hodgkin lymphoma (NHL) that is characterized by the translocation t(11;14)(q13;q32) and a poor response to rituximab-anthracycline-based chemotherapy. Intensive regimens offer durable response, but a subgroup of MCL patients will not be eligible for those regimens and hence are ca...

Purpose: The histone-methyl transferase EZH2, catalytic subunit of the PRC2 complex involved in transcriptional regulation is mutated in approximately 25% of germinal center B-cell lymphomas. Aberrant proliferative dependency on EZH2 activity can be targeted by the orally available EZH2 inhibitor tazemetostat (EPZ-6438). We report the results of t...

Composite and sequential lymphomas involving both classical Hodgkin lymphoma (CHL) and primary mediastinal B‐cell lymphoma (PMBCL) are rare phenomena. Beyond the relevant biological interest raised by these cases, treatments and outcome data are poorly covered in the recent literature. This retrospective analysis describes the pathological and clin...

Disclosures: Sarkozy: Takeda: Research Funding. Salles:Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis, Servier, AbbVie, Karyopharm, Kite, MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Autolus: Consultan...

Introduction: The recently developed DLBCL90 NanoString assay robustly distinguishes primary mediastinal large B-cell lymphoma (PMBCL) from diffuse large B-cell lymphoma (DLBCL), as well as cell-of-origin (COO) subtypes of DLBCL (ABC, GCB, unclassified) and cases with a Double-Hit (DHIT) signature (Ennishi D., JCO 2019). When this assay was applied...

Single-cell RNA sequencing has enabled the decomposition of complex tissues into functionally distinct cell types. Often, investigators wish to assign cells to cell types through unsupervised clustering followed by manual annotation or via ‘mapping’ to existing data. However, manual interpretation scales poorly to large datasets, mapping approaches...

Diffuse large B‐cell lymphoma (DLBCL) is the most common histologic subtype of non‐Hodgkin lymphoma and is notorious for its clinical heterogeneity. Patient outcomes can be predicted by cell‐of‐origin (COO) classification, demonstrating that the underlying transcriptional signature of malignant B‐cells informs biological behavior in the context of...

A new member of Anelloviridae, named torque teno mini virus (TTMV)-SH, was recently identified in the serum of three Hodgkin’s lymphoma patients suggesting that TTMV-SH may be associated with this type of hematological malignancy. We investigated by metagenomic analysis the presence of TTMV-SH-related viruses in plasma samples (n = 323) collected f...

Non-follicular small cell lymphomas include several entities whose clinical and pathological descriptions have been refined in the last 20 years. MALT lymphoma, developed at the expense of lymphoid tissue associated with the mucosa, is usually localized to a given organ, but can also disseminate. Some patients with MALT lymphoma can be treated by e...

Primary mediastinal large B-cell lymphoma (PMBL) represents a clinically and pathologically distinct subtype of large B-cell lymphomas. Furthermore, molecular studies, including global gene expression profiling, have provided evidence that PMBL is more closely related to classical Hodgkin lymphoma (cHL). Although targeted sequencing studies have re...

Aberrant activation of the JAK-STAT pathway is a hallmark of a variety of lymphomas and can alter the lymphoma cells secretome and the composition of the tumor microenvironment (TME). The up-regulation of the immune regulatory chemokine CCL17 has been shown to be mediated by STATs-dependent mechanism in primary mediastinal B cell lymphoma (PMBCL)....

Background Mutations in cohesin complex genes have been described commonly in several types of cancer, with an incidence of 8% in myeloid diseases and myelodysplastic syndromes (MDS), and have been linked to marrow fibrosis by our group in a prior publication (Ramos F et al . Oncotarget 2016). However, their clinical impact is still undetermined....

Single-cell RNA sequencing (scRNA-seq) has transformed biomedical research, enabling decomposition of complex tissues into disaggregated, functionally distinct cell types. For many applications, investigators wish to identify cell types with known marker genes. Typically, such cell type assignments are performed through unsupervised clustering foll...

Gray-zone lymphoma (GZL) with features intermediate between classic Hodgkin lymphoma (cHL) and large B-cell lymphoma (LBCL) was introduced as a provisional entity into the World Health Organization classification in 2008. However, as diagnostic criteria are imprecise, reliable identification of GZL cases remains challenging. Here, we describe the h...

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INTRODUCTION There is a growing interest in analyzing the biological and clinical variables that might help in identifying patients at risk of histological transformation (HT), a critical event that can still lead to reduced survival in patients with follicular lymphoma (FL). As part of the Aristotle study, we have previously reported that the risk...

Introduction: Epigenetic modulation of histones plays a critical role in lymphomagenesis. The histone-methyl transferase EZH2 is the catalytic subunit of the PRC2 complex, and plays an important role in transcriptional repression during germinal center formation. Mutations in EZH2 have been observed in ~20% of DLBCL and aberrant EZH2 activity (in t...

Introduction: standard treatment for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is high-dose chemotherapy followed by autologous stem-cell transplantation (ASCT) but this strategy is not appropriate for elderly DLBCL patients (pts) related to a high risk of toxicities. Multiple chemotherapy regimens had been developed for heavi...

Purpose International Prognostic Index (IPS) is the most widely used risk stratification index for advanced stage Hodgkin's lymphoma (HL). The use of (18F)-fluorodeoxyglucose PET/CT at diagnosis allows a better characterization of extra-nodal involvement (ENI). We investigated if the type of ENI could affect the prognosis of stage IV HL patients di...

Introduction : Follicular lymphoma (FL) is a clinically and genetically heterogeneous disease with highly variable patient outcomes. Recently, Huet et al. proposed a 23-gene expression-based risk score for predicting progression-free survival (PFS) in FL patients treated with rituximab and chemotherapy (Huet et al. Lancet Oncology 2018). The m7-FLI...

Purpose: Although the life expectancy of patients with follicular lymphoma (FL) has increased, little is known of their causes of death (CODs) in the rituximab era. Patients and methods: We pooled two cohorts of newly diagnosed patients with FL grade 1-3A. Patients were enrolled between 2001 and 2013 in two French referral institutions (N = 734;...

Over recent years, there has been increasing interest in the use of the anelloviruses, the major component of the human virome, for the prediction of post-transplant complications such as severe infections. Due to an important diversity, the comprehensive characterization of this viral family over time has been poorly studied. To overcome this chal...

We present results of a prospective, multicenter, phase II study evaluating rituximab, bendamustine, bortezomib and dexamethasone as first-line treatment for mantle cell lymphoma patients of 65 years or older. A total of 74 patients were enrolled (median age, 73 years). Patients received a maximum of 6 treatment cycles at 28 day intervals. The prim...

Background: Histological transformation of follicular lymphoma to aggressive lymphoma is a serious event with a substantial effect on patient outcome. The aim of the Aristotle study was to assess the effect of rituximab on the risk of histological transformation and its outcome. Methods: 11 cooperative groups or institutions across Europe contri...

Diffuse large B cell lymphoma represents the most common type of non-Hodgkin lymphoma. Although the curability rate is high, around 40% of patients will relapse or exhibit refractory disease. To obtain long-term disease-free survival after relapse, an intensive salvage regimen followed by autologous steam cell transplant remains the standard of car...

In the rituximab era, one‐third of diffuse large B‐cell lymphoma patients experience relapse/refractory disease after first‐line anthracycline‐based immunochemotherapy. Optimal management remains an unmet medical need. The aim of this study was to report the outcomes of a cohort of refractory patients according to their patterns of refractoriness a...

High throughput sequencing is increasingly used in the diagnosis of lymphoid neoplasms, in order to establish the diagnosis, to precise the prognosis or to search for molecular target for therapy. In order to standardize the diagnostic procedure in France, the Lymphoma Study Association (LYSA) and the Groupe des biologistes moléculaires des hémopat...

The aim of this retrospective cohort study was to investigate the incidence of delayed methotrexate elimination in patients treated with high-dose methotrexate (≥1 g/m2) for haematological malignancy and to identify the impact of interacting drugs, especially proton-pump inhibitors (PPIs) and ranitidine. All patients treated with high-dose methotre...

Les lymphomes B diffus à grandes cellules (LBDGC) comportant un réarrangement chromosomique du gène MYC représentent environ 10 % des LBDGC. Ils sont souvent réfractaires aux thérapeutiques standards et associés à un pronostic péjoratif. L’indication d’une étude cytogénétique par hybridation in situ en fluorescence (FISH) pour identifier ces cas n’...

Recent advances in next-generation sequencing (NGS) have enabled the quantitation of circulating tumour DNA (ctDNA) encoding the clonal rearranged V(D)J immunoglobulin locus. We aimed to evaluate the clonal heterogeneity of follicular lymphoma (FL) in the tumour and the plasma at diagnosis and to assess the prognostic value of the ctDNA level. Plas...

INTRODUCTION: The benefits of ibrutinib (ibr) have been demonstrated by the phase 3 RESONATE and RESONATE-2 trials for patients (pts) with R/R and TN (≥ 65 years) CLL, respectively. In these studies, ibr showed significantly improved progression-free survival (PFS) and overall survival (OS) vs approved comparators (ofatumumab [ofa] in RESONATE and...

Although progression free survival and overall survival of patients with Hodgkin lymphoma (HL) has improved with modern treatment in the past 10 years, 10 % of patients will fail to conventional therapy and die of their lymphoma. The search of new prognostic factors for identifying these high risk patients at diagnosis of HL remains challenging in...

Treatment of relapsed/refractory peripheral T-cell lymphoma (R/R PTCL) remains an unmet medical need, as treatment with polychemotherapy is associated with poor outcome. With the exception of Brentuximab vedotin in systemic anaplastic large cell lymphomas, recent FDA approved drugs to treat R/R PTCL showed limited activity, with a 30% overall respo...

Temsirolimus has shown clinical activity in heavily pretreated patients with mantle cell lymphoma (MCL) leading to evaluate tolerability and efficacy of combinations regimens. The T3 trial is a multicenter, Phase IB, dose escalation study (3+3) of Temsirolimus administered in combination with three chemotherapy regimens in relapse or refractory (R/...

Background There is no standard treatment for R/R MCL that fail first line treatment. Non cross resistant regimens are usually used, which provided sometimes good overall response rate (until 93%) but with a minor disease control (PFS<2years). [1] The main objective of these salvage regimens is to bypass disease resistance, to obtain more profound...

Although rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment for patients with diffuse large B-cell lymphoma (DLBCL), ∼30% to 50% of patients are not cured by this treatment, depending on disease stage or prognostic index. Among patients for whom R-CHOP therapy fails, 20% suffer from primary...

Mediastinal grey zone lymphoma, B cell lymphomas with intermediate features between classical Hodgkin lymphoma and primary mediastinal B cell lymphoma, are not well described in the literature. We report the clinical characteristics and outcomes of a large retrospective series of 99 cases centrally reviewed by a panel of hematopathologists, with a...