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INTRODUCTION: In the treatment of advanced Hodgkin lymphoma (aHL), based on guidelines a multitude of treatment options are available. The availability of PET-guided decision-making and new therapeutic agents increase the complexity of the decision-making process. METHODS: Thirteen experts of Swiss university and cantonal hospitals in Switzerland were asked to describe their institutional decision-making practice in aHL. Variables influencing the decision-making process were identified, standardized, and converted into decision trees for analysis of consent and discrepancies. The algorithms of all participating experts were analyzed with the objective consensus methodology. RESULTS: Four decision criteria (age, fertility preservation, fitness, and interim PET) and 12 unique treatment regimens were identified. Consensus for the treatment of aHL for young and fit, as well as for older patients without comorbidity, was found. Large heterogeneity was identified with use of a variety of different regimens for unfit patients with aHL and for young female patients with a desire of fertility preservation. CONCLUSIONS: Four major decision criteria were identified allowing the representation of expert's approach to first-line treatment of aHL. Among Swiss experts, consensus for a PET-guided curative treatment of aHL was identified. The use of a multitude of treatment regimens was observed for older and comorbid (unfit) aHL patients, highlighting the need for clinical trials and recommendations for this group of patients.
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Doença de Hodgkin , Humanos , Doença de Hodgkin/tratamento farmacológico , Consenso , SuíçaRESUMO
Post-transplant lymphoproliferative disorders (PTLD) represent a typical complication of transplant recipients. Their incidence varies according to the recipient's characteristics and the type of transplanted organ. Their pathogenesis is strongly related to a disbalance between reduced T-cell immune surveillance to avoid graft rejection, and the reactivation of the oncogenic Epstein-Barr virus (EBV) within B lymphocytes, leading to uncontrolled B-cell proliferation and malignant transformation. PTLD represent a spectrum of various histological entities with distinct prognosis. Clinical management mainly focuses on their surveillance and therapeutic strategy is risk-adapted. This review aims to shed light on these rare pathologies whose early detection could greatly improve the prognosis of transplant patients.
Les maladies lymphoprolifératives post-transplantation (PTLD) représentent une complication classique des receveurs d'organe. Leur incidence varie selon le profil du receveur et le type d'organe transplanté. La pathogenèse est fortement associée à un déséquilibre entre la diminution de la surveillance immunitaire T requise pour éviter le rejet du greffon et la réactivation du virus oncogénique Epstein-Barr (EBV) au sein des lymphocytes B, amenant à leur prolifération incontrôlée et à la transformation maligne. Elles représentent un spectre d'entités histologiques au pronostic variable, dont la prise en charge se concentre sur la surveillance ; la stratégie thérapeutique étant dictée par le risque. Cet article vise à mettre en lumière ces pathologies rares dont la détection précoce pourrait améliorer le pronostic des patients transplantés.
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Infecções por Vírus Epstein-Barr , Transplante de Rim , Transtornos Linfoproliferativos , Transplante de Órgãos , Humanos , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/epidemiologia , Herpesvirus Humano 4/fisiologia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/etiologia , Transplante de Órgãos/efeitos adversos , Transplante de Rim/efeitos adversosRESUMO
Pretransplant Deauville score (DS) is an imaging biomarker used for risk stratification in relapsed/refractory classical Hodgkin lymphoma (cHL). However, the prognostic value of residual metabolic tumor volume (rMTV) in patients with DS 4-5 has been less well characterized. We retrospectively assessed 106 patients with relapsed/refractory cHL who underwent autologous stem cell transplantation. Pretransplant DS was determined as 1-3 (59%) and 4-5 (41%), with a markedly inferior event-free survival (EFS) in patients with DS 4-5 (hazard ratio [HR], 3.14; p = .002). High rMTV41% (rMTVhigh , ≥4.4 cm3 ) predicted significantly poorer EFS in patients with DS 4-5 (HR, 3.70; p = .014). In a multivariable analysis, we identified two independent factors predicting treatment failure: pretransplant DS combined with rMTV41% and disease status (primary refractory vs. relapsed). These two factors allow to stratify patients into three groups with divergent 2-year EFS: 89% for low-risk (51%; relapsed disease and either pretransplant DS 1-3 or DS 4-5/rMTVlow ; HR 1), 65% for intermediate-risk (28%; refractory disease and either DS 1-3 or DS 4-5/rMTVlow ; HR 3.26), and 45% for high-risk (21%; DS 4-5/rMTVhigh irrespective of disease status; HR 7.61) groups. Pretransplant DS/rMTV41% combination and disease status predict the risk of post-transplant treatment failure and will guide risk-stratified approaches in relapsed/refractory cHL.
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Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica , Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/patologia , Humanos , Recidiva Local de Neoplasia , Estudos Retrospectivos , Medição de Risco , Transplante Autólogo , Carga TumoralRESUMO
Chronic lymphocytic leukemia (CLL) is an indolent lymphoproliferative disorder commonly seen in the elderly. Its diagnosis is often incidental. Treatment is not always required, and a clinical and biological follow-up may be sufficient. However, progressive CLL may result in shortened life expectancy and significant complications. It is therefore critical to precisely stratify CLL prognosis to guide therapeutic choices accordingly. Therapeutic options have largely evolved in the past years and current molecular biomarkers allow a better risk stratification, leading to a significant improvement of survival. We summarize herein modern diagnostic and therapeutic management of CLL.
La leucémie lymphoïde chronique (LLC) est une maladie lymphoproliférative indolente fréquente, affectant surtout le sujet âgé. Souvent diagnostiquée fortuitement, elle ne nécessite pas toujours de traitement, une surveillance simple pouvant suffire. Néanmoins, les formes évolutives de la maladie sont responsables d'une diminution de l'espérance de vie et de complications significatives. Il est essentiel d'évaluer précisément le risque évolutif pour orienter au mieux la prise en charge. Ces dernières années, la panoplie de thérapies disponibles s'est étoffée et la découverte de biomarqueurs pronostiques a permis de mieux identifier les patients à risque, améliorant ainsi significativement leur survie. Nous souhaitons revoir, ici, les principaux aspects de la prise en charge diagnostique et thérapeutique de la LLC.
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Antineoplásicos , Leucemia Linfocítica Crônica de Células B , Idoso , Antineoplásicos/uso terapêutico , Células Clonais , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Linfócitos , PrognósticoRESUMO
Ovarian cancer is the first cause of death by gynecological cancer. Most of the patients are diagnosed with peritoneal carcinomatosis that represents a therapeutic challenge. Its management implies maximal cytoreductive surgery with survival benefit. Over the last three decades, several strategies of intra-peritoneal chemotherapy have been investigated. This includes intra-peritoneal adjuvant chemotherapy that is used mainly in North America, hyperthermic intraperitoneal chemotherapy (HIPEC) and more recently pressurized intraperitoneal aerosol chemotherapy (PIPAC). In the current article, we review the evidence in favor of each therapeutic approach, and we propose treatment algorithms depending on the clinical situation of ovarian cancer patients: upfront, platinum-sensitive and platinum-resistant relapse.
Le cancer de l'ovaire est la première cause de décès par cancer gynécologique. La plupart des patientes sont diagnostiquées au stade de carcinose péritonéale qui représente un défi thérapeutique. Sa prise en charge chirurgicale implique une cytoréduction maximaliste. Au cours des 30 dernières années, plusieurs stratégies de chimiothérapie intrapéritonéale ont été testées afin d'améliorer le contrôle de la carcinose péritonéale. Il s'agit des chimiothérapies intrapéritonéale adjuvante utilisée surtout en Amérique du Nord, hyperthermique intrapéritonéale (CHIP) et intrapéritonéale pressurisée en aérosols (PIPAC). Dans cet article, nous reprenons les données de la littérature sur chacune de ces trois approches thérapeutiques et proposons des algorithmes décisionnels selon la situation clinique des patientes traitées pour un cancer de l'ovaire : au diagnostic, récidive platine-sensible et platine-résistante.
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Carcinoma , Hipertermia Induzida , Neoplasias Ovarianas , Neoplasias Peritoneais , Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma/terapia , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Recidiva Local de Neoplasia/terapia , Neoplasias Ovarianas/terapia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgiaRESUMO
Monoclonal plasma cell gammopathies (MPCG) describe several forms of abnormal plasma cell proliferation. Their prevalence increases with age. Initially asymptomatic, MPCG can evolve differently and they can tend towards more advanced stages, sometimes associated with severe complications. Most patients are diagnosed by their general practitioner, who then offers a joint follow-up with the specialist. It therefore seems important to review the diagnostic and therapeutic management of MPCG, as well as their potential complications and treatments adverse effects.
Les gammapathies monoclonales plasmocytaires (GMP) regroupent plusieurs pathologies secondaires à une anomalie de la prolifération plasmocytaire. Leur prévalence augmente avec l'âge. Initialement asymptomatiques, les GMP ont un potentiel évolutif variable pouvant néanmoins tendre vers des stades plus avancés grevés de complications, parfois sévères. La plupart des patients diagnostiqués le sont par leur médecin de premier recours, qui réalise ensuite souvent un suivi conjoint avec le spécialiste. Il nous semble donc important de parcourir les prises en charge diagnostiques et thérapeutiques des GMP, ainsi que de sensibiliser le lecteur à leurs potentielles complications et aux effets indésirables des traitements.
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Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Paraproteinemias , HumanosRESUMO
Every year, cancer affects more than a million adolescents and young adults (AYA) in high-income countries. AYA patients represent a heterogeneous but distinct population, aged from 15 to 39 (-45) years old, among which different types of cancer are found compared to the ones affecting children and older adults. Although these pathologies remain the leading cause of death in the AYA age range, the survival rate in this population has significantly improved in recent years, averaging 85%. The aim of this article is to review one major issue in AYA survivors, which is the risk of impaired fertility due to oncological treatments, and the different strategies available to address this problem.
Chaque année, le cancer touche plus d'un million de jeunes adultes (AJA) dans les pays à revenus élevés. Les AJA représentent une population hétérogène mais distincte de patients, âgés de 15 à 45 ans, chez lesquels on retrouve des cancers qui diffèrent de ceux rencontrés chez les enfants ou les personnes plus âgées. Quoique ces pathologies restent la première cause de mortalité dans cette tranche d'âge, la survie de ces patients s'est considérablement améliorée ces dernières années avec un taux de guérison atteignant 85 %. Cet article a pour but d'aborder une question d'importance majeure chez les survivants en âge de procréer, à savoir le risque d'altération de la fertilité lié aux traitements oncologiques, ainsi que les différentes stratégies à disposition pour pallier cette problématique.
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Fertilidade , Infertilidade , Neoplasias , Adolescente , Adulto , Criança , Humanos , Infertilidade/etiologia , Oncologia , Neoplasias/complicações , Neoplasias/terapia , Taxa de Sobrevida , Sobreviventes , Adulto JovemRESUMO
Immune checkpoint blockade (ICB) has indeed transformed the outlook for many advanced-stage solid tumors, yet its effectiveness in hematological malignancies has been particularly limited, with success predominantly demonstrated in classical Hodgkin lymphoma (cHL) and immune-privilege subtypes of non-Hodgkin lymphoma (NHL). In this report, we present an impactful case of a 71-year-old man grappling with refractory follicular lymphoma (rFL) that had progressed to a high-grade lymphoma, leaving no conventional treatment options on the table. Notably, the histological examination of the tumor tissue revealed a markedly elevated PD-L1 expression, illuminating the potential for immunotherapy to be effective. Additionally, comprehensive gene sequencing unveiled a moderate tumor mutational burden (TMB), deepening our understanding of the tumor's molecular intricacies. As his health declined with no access to cell therapies or clinical trials at that time, a combination treatment of PD-1 ICB and an anti-CD20 drug surprisingly led to a significant improvement in his condition and long-term remission. While PD-1 ICB therapy has historically shown limited responses in non-Hodgkin lymphomas (NHLs), this case serves as a beacon of optimism, underscoring the promise of combining immunotherapy modalities and the potential of comprehensive molecular assessments in charting innovative treatments for extensively treated NHL patients. The quest for predictive biomarkers to gauge treatment response remains a formidable challenge. This report serves as a testament to the ever-evolving landscape of cancer treatment, where precision medicine and immunotherapy continue to unlock new possibilities for those confronting the most challenging malignancies.
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BACKGROUND: Tumor lysis syndrome (TLS) is a potentially life-threatening condition resulting from the rapid destruction of malignant cells, leading to electrolyte imbalances and severe complications, such as acute kidney injury, arrhythmias, and seizures. TLS can be managed through hyperhydration, urate-lowering treatments, and a steroid prophase strategy. AIMS: This study aims to explore the impact of fractionated rituximab, an anti-CD20 antibody, on the occurrence and severity of TLS during the initial cycle in patients with aggressive B-cell non-Hodgkin lymphoma (B-NHL). METHODS: Data was retrospectively collected from 94 of 186 patients. RESULTS: Among the 94 patients included in the analysis, the median age was 70. Histologies were diffuse large B-cell lymphoma (75%), Burkitt lymphoma (13%) and high-grade B-cell lymphoma (8%). The majority were at an advanced stage (93%) with a high IPI score (75%). Most patients received anthracycline-containing regimens (72%) and prophylactic allopurinol (83%) and/or rasburicase (26%). Steroid prophase was administered to 82% of patients. The study identified one clinical TLS case and six laboratory TLS cases. Significant TLS factors included BL histology, elevated baseline LDH (⟩500 U/l), and rasburicase usage. Infusion reactions were rare (3%). Median progression-free survival was 2.6 years, and 2-year overall survival was 33%, irrespective of TLS occurrence. CONCLUSION: In this real-life study, clinical TLS occurrence was low (1%). TLS appeared more frequent in BL but did not impact overall survival. Fractionated initial rituximab dosing in addition to preventive strategies is a feasible approach in preventing clinical TLS, warranting further prospective investigation.
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Rituximab , Síndrome de Lise Tumoral , Humanos , Síndrome de Lise Tumoral/etiologia , Síndrome de Lise Tumoral/prevenção & controle , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Masculino , Feminino , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Adulto , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/patologia , Linfoma de Células B/mortalidadeRESUMO
Immune checkpoint blockade (ICB) has revolutionized the prognosis of several advanced-stage solid tumors. However, its success has been far more limited in hematological malignancies and is mostly restricted to classical Hodgkin lymphoma (cHL) and primary mediastinal B cell lymphoma (PMBCL). In patients with non-Hodgkin lymphoma (NHL), response to PD-1/PD-L1 ICB monotherapy has been relatively limited, although some subtypes are more sensitive than others. Numerous predictive biomarkers have been investigated in solid malignancies, such as PD-L1 expression, tumor mutational burden (TMB) and microsatellite instability (MSI), among others. This review aims to appraise the current knowledge on PD-1/PD-L1 ICB efficacy in lymphoma when used either as monotherapy or combined with other agents, and describes potential biomarkers of response in this specific setting.
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INTRODUCTION: Intraperitoneal dissemination is a major problem resulting in very poor prognosis and a rapid marked deterioration in the quality of life of patients. Pressurised intraperitoneal aerosol chemotherapy (PIPAC) is an emergent laparoscopic procedure aiming to maximise local efficacy and to reduce systemic side effects. METHODS AND ANALYSIS: Nab-PIPAC, a bicentre open-label phase IB, aims to evaluate safety of nab-paclitaxel and cisplatin association using in patients with peritoneal carcinomatosis (PC) of gastric, pancreatic or ovarian origin as ≥1 prior line of systemic therapy. Using a 3+3 design, sequential intraperitoneal laparoscopic application of nab-paclitaxel (7.5, 15, 25, 37.5, 52.5 and 70 mg/m2) and cisplatin (10.5 mg/m2) through a nebuliser to a high-pressure injector at ambient temperature with a maximal upstream pressure of 300 psi. Treatment maintained for 30 min at a pressure of 12 mm Hg and repeated4-6 weeks intervals for three courses total.A total of 6-36 patients are expected, accrual is ongoing. Results are expected in 2024.The primary objective of Nab-PIPAC trial is to assess tolerability and safety of nab-paclitaxel and cisplatin combination administered intraperitoneally by PIPAC in patients with PC of gastric, pancreatic or ovarian origin. This study will determine maximum tolerated dose and provide pharmacokinetic data. ETHIC AND DISSEMINATION: Ethical approval was obtained from the ethical committees of Geneva and Vaud (CCER-2018-01327). The study findings will be published in an open-access, peer-reviewed journal and presented at relevant conferences and research meetings. TRIAL REGISTRATION NUMBER: NCT04000906.
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Cisplatino , Neoplasias Peritoneais , Humanos , Cisplatino/uso terapêutico , Cavidade Peritoneal/patologia , Doxorrubicina , Qualidade de Vida , Aerossóis , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos Fase I como AssuntoRESUMO
BACKGROUND: Carriers of germline pathogenic variants of the BRCA1 gene (gBRCA1) tend to have a higher incidence of haematological toxicity upon exposure to chemotherapy. We hypothesised that the occurrence of agranulocytosis during the first cycle of (neo-)adjuvant chemotherapy (C1) in breast cancer (BC) patients could predict gBRCA1 pathogenic variants. PATIENTS AND METHODS: The study population included non-metastatic BC patients selected for genetic counselling at Hôpitaux Universitaires de Genève (Jan. 1998 to Dec. 2017) with available mid-cycle blood counts performed during C1. The BOADICEA and Manchester scoring system risk-prediction models were applied. The primary outcome was the predicted likelihood of harbouring gBRCA1 pathogenic variants among patients presenting agranulocytosis during C1. RESULTS: Three hundred seven BC patients were included: 32 (10.4%) gBRCA1, 27 (8.8%) gBRCA2, and 248 (81.1%) non-heterozygotes. Mean age at diagnosis was 40 years. Compared with non-heterozygotes, gBRCA1 heterozygotes more frequently had grade 3 BC (78.1%; p = 0.014), triple-negative subtype (68.8%; p <0.001), bilateral BC (25%; p = 0.004), and agranulocytosis following the first cycle of (neo-)adjuvant chemotherapy (45.8%; p = 0.002). Agranulocytosis and febrile neutropenia that developed following the first cycle of chemotherapy were independently predictive for gBRCA1 pathogenic variants (odds ratio: 6.1; p = 0.002). The sensitivity, specificity, positive predictive value, and negative predictive value for agranulocytosis predicting gBRCA1 were 45.8% (25.6-67.2%), 82.8% (77.5-87.3%), 22.9% (6.1-37.3%), and 93.4% (88.9-96.4%), respectively. Agranulocytosis substantially improved the positive predictive value of the risk-prediction models used for gBRCA1 evaluation. CONCLUSION: Agranulocytosis following the first cycle of (neo-)adjuvant chemotherapy is an independent predictive factor for gBRCA1 detection in non-metastatic BC patients.
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Neoplasias da Mama , Humanos , Adulto , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/epidemiologia , Estudos Retrospectivos , Proteína BRCA2/genética , Mutação em Linhagem Germinativa , Células Germinativas , Proteína BRCA1/genéticaRESUMO
BRCA1 and BRCA2 play a central role in DNA repair and their germline pathogenic variants (gBRCA) confer a high risk for developing breast and ovarian cancer. Standard chemotherapy regimens for these cancers include DNA-damaging agents. We hypothesized that gBRCA carriers might be at higher risk of developing chemotherapy-related hematologic toxicity and therapy-related myeloid neoplasms (t-MN). We conducted a retrospective study of women newly diagnosed with invasive breast or ovarian cancer who were screened for gBRCA1/gBRCA2 at Geneva University Hospitals. All patients were treated with (neo-)adjuvant chemotherapy. We evaluated acute hematologic toxicities by analyzing the occurrence of febrile neutropenia and severe neutropenia (grade 4) at day 7-14 of the first cycle of chemotherapy and G-CSF use during the entire chemotherapy regimen. Characteristics of t-MN were collected. We reviewed medical records from 447 patients: 58 gBRCA1 and 40 gBRCA2 carriers and 349 non-carriers. gBRCA1 carriers were at higher risk of developing severe neutropenia (32% vs. 14.5%, p = 0.007; OR = 3.3, 95% CI [1.6-7], p = 0.001) and of requiring G-CSF for secondary prophylaxis (58.3% vs. 38.2%, p = 0.011; OR = 2.5, 95% CI [1.4-4.8], p = 0.004). gBRCA2 carriers did not show increased acute hematologic toxicities. t-MN were observed in 2 patients (1 gBRCA1 and one non-carrier). Our results suggested an increased acute hematologic toxicity upon exposure to chemotherapy for breast and ovarian cancer among gBRCA1 but not gBRCA2 carriers. A deeper characterization of t-MN is warranted with the recent development of PARP inhibitors in frontline therapy in gBRCA breast and ovarian cancer.
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Neoplasias da Mama , Neutropenia , Neoplasias Ovarianas , Humanos , Feminino , Estudos Retrospectivos , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Mutação em Linhagem Germinativa , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/genética , Células Germinativas/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genéticaRESUMO
While more than half of non-Hodgkin lymphomas (NHL) can be cured with modern frontline chemoimmunotherapy regimens, outcomes of relapsed and/or refractory (r/r) disease in subsequent lines remain poor, particularly if considered ineligible for hematopoietic stem cell transplantation. Hence, r/r NHLs represent a population with a high unmet medical need. This therapeutic gap has been partially filled by adoptive immunotherapy. CD19-directed autologous chimeric antigen receptor (auto-CAR) T cells have been transformative in the treatment of patients with r/r B cell malignancies. Remarkable response rates and prolonged remissions have been achieved in this setting, leading to regulatory approval from the U.S. Food and Drug Administration (FDA) of four CAR T cell products between 2017 and 2021. This unprecedented success has created considerable enthusiasm worldwide, and autologous CAR T cells are now being moved into earlier lines of therapy in large B cell lymphoma. Herein, we summarize the current practice and the latest progress of CD19 auto-CAR T cell therapy and the management of specific toxicities and discuss the place of allogeneic CAR T development in this setting.
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Antibody-drug conjugates (ADCs) are a recent, revolutionary approach for malignancies treatment, designed to provide superior efficacy and specific targeting of tumor cells, compared to systemic cytotoxic chemotherapy. Their structure combines highly potent anti-cancer drugs (payloads or warheads) and monoclonal antibodies (Abs), specific for a tumor-associated antigen, via a chemical linker. Because the sensitive targeting capabilities of monoclonal Abs allow the direct delivery of cytotoxic payloads to tumor cells, these agents leave healthy cells unharmed, reducing toxicity. Different ADCs have been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of a wide range of malignant conditions, both as monotherapy and in combination with chemotherapy, including for lymphoma patients. Over 100 ADCs are under preclinical and clinical investigation worldwide. This paper it provides an overview of approved and promising ADCs in clinical development for the treatment of lymphoma. Each component of the ADC design, their mechanism of action, and the highlights of their clinical development progress are discussed.
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The evolving CoViD-19 pandemic has raised unprecedented challenges for physicians who face significant constraints in medical resources and cancer therapies. The management of patients with lymphoma represents a unique challenge given the heterogeneity of the patient population and treatment goals as well as the myriad choices of therapy available to clinicians. Adaptation in clinical practice with the goal of maintaining appropriate continuity and quality of care while mitigating exposure risk has forced clinicians around the world to develop new standards of practice and can pose difficult ethical choices in vulnerable patient populations. Based on recommendations formulated by several medical groups and societies, this article provides an overview of the general and specific practical considerations that apply to the care of lymphoma patients during the outbreak. We hope to provide a practical framework to help guide physicians in their therapeutic choices and facilitate the ongoing management of this specific patient population.
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COVID-19 , Linfoma , Médicos , Humanos , Linfoma/diagnóstico , Linfoma/epidemiologia , Linfoma/terapia , Pandemias , SARS-CoV-2RESUMO
Recent results of randomized phase III studies of FDG-PET-adapted therapy for advanced Hodgkin lymphoma (HL) have clearly demonstrated benefit to alteration of treatment according to interim response, in particular regarding reducing toxicity while maintaining efficacy. However, these studies have differences in design including initial chemotherapy regimen, PET response criteria, patient populations enrolled, and inclusion of radiation, and report different results regarding efficacy and toxicities, which makes cross-trial comparisons difficult. Practitioners are presented with deciding which of these approaches will provide the optimum outcome, balancing toxicity and efficacy, and for which patient with advanced-stage HL. This review summarizes the observations reported from these trials and provides context to help guide physicians and patients in treatment decisions for advanced HL.
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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BRCA1/BRCA2 genes play a central role in DNA repair and their mutations increase sensitivity to DNA-damaging agents. There are conflicting data regarding the prognostic value of BRCA germline mutations in breast cancer (BC) patients. We collected clinical, pathological and genetic data of a cohort 925 BC patients preselected for genetic screening and treated with neoadjuvant or adjuvant chemotherapy, of whom 266 were BRCA carriers. Overall, 171 women carried a BRCA1 mutation, 95 carried a BRCA2 mutation, and 659 were non-carriers. In the entire cohort, there was a prolonged disease-free survival (DFS) for BRCA carriers (hazard ratio (HR) = 0.63; 95% confidence interval (CI), 0.44-0.90 for BRCA1; HR = 0.72; 95%CI, 0.47-1.1 for BRCA2; p = 0.020) and a trend toward prolonged disease-specific survival (DSS; HR = 0.65; 95%CI, 0.40-1.1 for BRCA1; HR = 0.78; 95%CI, 0.44-1.38 for BRCA2; p = 0.19) though not statistically significant. In the TNBC group, BRCA carriers had prolonged DFS (adjusted HR = 0.50; 95%CI, 0.28-0.89 for BRCA1; adjusted HR = 0.37; 95%CI, 0.11-1.25, for BRCA2; p = 0.034) and DSS (adjusted HR = 0.42; 95%CI, 0.21-0.82 for BRCA1; adjusted HR = 0.45; 95%CI, 0.11-1.9 for BRCA2; p = 0.023). In the non-TNBC group, the BRCA1 or BRCA2 mutations did not have any impact on survival. These results suggest that BRCA1/BRCA2 germline mutations are associated with prolonged survival only if women were diagnosed with TNBC.