Valeur pronostique de la tomographie par émission de positons au fluorodeoxyglucose (TEP-FDG) avant intensification thérapeutique et autogreffe de cellules souches hématopoïétiques chez des patients présentant un lymphome folliculaire en rechute ou réfractaire

La prise en charge des patients jeunes présentant un lymphome folliculaire en rechute ou réfractaire comprend classiquement un traitement de rattrapage par immuno-chimiothérapie suivi d'une intensification thérapeutique et autogreffe de cellules souches hématopoïétiques (CSH). Plusieurs études ont rapporté la valeur pronostique de la TEP-FDG avant autogreffe de CSH en cas de lymphome de Hodgkin en rechute ou réfractaire. Objectif : Évaluer la valeur pronostique de la TEP-FDG après traitement de rattrapage et avant intensification thérapeutique chez des patients présentant un lymphome folliculaire en rechute ou réfractaire, chimio-sensible. Patients et méthodes : Cinquante-neuf patients présentant un lymphome folliculaire en première rechute ou réfractaire après R-CHOP ont été inclus dans cette étude rétrospective. Tous les patients étaient répondeurs à l'immuno-chimiothérapie de rattrapage et ont bénéficié d'une intensification thérapeutique et autogreffe de CSH dans trois centres français membres du LYSA (LYmphoma Study Association), entre novembre 2007 et janvier 2013. Résultats : La survie sans progression (PFS) et la survie globale (OS) à 3 ans pour l'ensemble de la population sont respectivement de 63.1% [50.9-78.3] et 90.5% [82.8-98.8] et ne sont pas impactées par le score FLIPI à la rechute, le conditionnement d'autogreffe ni le traitement de rattrapage utilisé. En revanche, la réponse déterminée sur la TEP-FDG avant autogreffe impacte la PFS, quel que soit le critère d'évaluation utilisé. En effet, la PFS à 3 ans en cas de TEP positive sur les critères IHP 2007 est de 45.5% [26.6-77.8] versus 72.6% [58.5-90.0] (p=0.039). Lorsque la positivité de la TEP est définie par un score de Deauville ≥ 3, la PFS à 3 ans est de 42.8% [24.7-74.4] versus 74.9% [61.0-92.0] (p=0.02). Enfin, la PFS à 3 ans en cas de ASUVmax < 70% est de 13.3% [2.2-81.7] contre 72.4% [57.5-91.3] (p < 10-3). La TEP-FDG est un facteur prédictif de PFS en analyse multivariée lorsqu'elle est combinée au caractère réfractaire au R-CHOP. Conclusion : La réponse à l'immuno-chimiothérapie de rattrapage évaluée par TEP-FDG avant intensification thérapeutique est un facteur pronostique prometteur chez des patients présentant un lymphome folliculaire en première rechute après R-CHOP ou réfractaire chimio-sensible

Emerging Landscape of Immunotherapy for Primary Central Nervous System Lymphoma

Primary central nervous system lymphoma (PCNSL) is, mainly, a diffuse large B-cell lymphoma (DLBCL) with a non-germinal center B-cell (non-GCB) origin. It is associated with a poor prognosis and an unmet medical need. Immunotherapy has emerged as one of the most promising areas of research and is now part of the standard treatment for many solid and hematologic tumors. This new class of therapy generated great enthusiasm for the treatment of relapsed/refractory PCNSL. Here, we discuss the challenges of immunotherapy for PCNSL represented by the lymphoma cell itself and the specific immune brain microenvironment. We review the current clinical development from the anti-CD20 monoclonal antibody to CAR-T cells, as well as immune checkpoint inhibitors and targeted therapies with off-tumor effects on the brain microenvironment. Perspectives for improving the efficacy of immunotherapies and optimizing their therapeutic role in PCNSL are suggested

CAR T-cells: current limitations and future developments

National audienceChimeric antigen receptor (CAR) T-cells represent a great breakthrough in the treatment of hematologic malignancies. To date, two different CAR T-cells have been approved for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma. Despite a remarkable efficacy, their use is limited by the occurrence of resistances and/or severe toxicities. A better understanding of these mechanisms and the progress in molecular intervention are paving the way for the development of new generations of CAR T-cells, with enhanced efficacy and/or reduced toxicity. Here, we review the mechanisms of resistance and toxicity, and the strategies which are envisioned to optimize CAR T-cell therapy

CAR-T cells and BiTEs in solid tumors: challenges and perspectives

International audienceChimeric antigen receptor (CAR)-modified T cells and BiTEs are both immunotherapies which redirect T cell specificity against a tumor-specific antigen through the use of antibody fragments. They demonstrated remarkable efficacy in B cell hematologic malignancies, thus paving the way for their development in solid tumors. Nonetheless, the use of such new drugs to treat solid tumors is not straightforward. So far, the results from early phase clinical trials are not as impressive as expected but many improvements are under way. In this review we present an overview of the clinical development of CAR-T cells and BiTEs targeting the main antigens expressed by solid tumors. We emphasize the most frequent hurdles encountered by either CAR-T cells or BiTEs, or both, and summarize the strategies that have been proposed to overcome these obstacles

Voltage-Gated Potassium Channel Antibody Paraneoplastic Limbic Encephalitis Associated with Acute Myeloid Leukemia

Among paraneoplastic syndromes (PNS) associated with malignant hemopathies, there are few reports of PNS of the central nervous system and most of them are associated with lymphomas. Limbic encephalitis is a rare neurological syndrome classically diagnosed in the context of PNS. We report the case of a 81-year-old man who presented with a relapsed acute myeloid leukemia (AML) with minimal maturation. He was admitted for confusion with unfavorable evolution as he presented a rapidly progressive dementia resulting in death. A brain magnetic resonance imaging, performed 2 months after the onset, was considered normal. An electroencephalogram showed non-specific bilateral slow waves. We received the results of the blood screening of neuronal autoantibodies after the patient's death and detected the presence of anti-voltage-gated potassium channel (VGKC) antibodies at 102 pmol/l (normal at <30 pmol/l). Other etiologic studies, including the screening for another cause of rapidly progressive dementia, were negative. To our knowledge, this is the first case of anti-VGKC paraneoplastic limbic encephalitis related to AML

Heterogeneous epigenetic regulation of HACE1 in Burkitt- Lymphoma-derived cells

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cghRA : a flexible workflow for CGH array analysis

International audienceAlthough Next Generation Sequencing technologies are becoming the new reference in whole genome analysis, there is still a need for more affordable methods like CGH arrays to compare genomic alterations in large sample series. Despite this need and the large collection of freely available un-interfaced algorithms and commercial software, biologists unfamiliar with command line interfaces and scripting lack a simple and efficient tool to handle such data.Here, we provide free cross-platform software, combining a user-friendly interface for pure biologists and an object-oriented command line interface for more advanced users. Its open-source R implementation offers a native interface to most of the published algorithms in the field, and a sharp learning curve to users familiar with this widespread scripting language. Aside from well-established algorithms, it includes original algorithms for copy number calling, recurring event definition and polymorphism filtering in a somatic context.The performances of these algorithms have been assessed in a series of 108 CGH arrays of Diffuse Large B-Cell Lymphoma (DLBCL), for which conventional caryotyping and quantitative PCR had also been performed. Copy number estimations made by cghRA proved to be more accurate than concurrent algorithms (GLAD, CGHcall), as compared to wet-lab validation. Recurring events highlighted by cghRA matched and extended the current knowledge of DLBCL genomics, while offering more flexibility than concurrent software (GISTIC, SRA). Finally, polymorphism annotation sensitivity was assessed in a public dataset of control samples, and specificity in a subset of arrays hybridized against matching normal DNA rather than a DNA pool

Final analysis of the phase IB part of the LOC-R01 trial, a non-comparative randomized phase IB/II study of escalating doses of lenalidomide and ibrutinib in association with R-MPV for patients with a newly diagnosed primary central nervous system lymphoma (PCNSL)

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