Publications by authors named "Pier-Luigi Zinzani"

Background: Classical Hodgkin's lymphoma (cHL) in adolescents between 15 and 18 years old shows a higher disease-related mortality, and the overall prognosis is worse than in both children and adults.

Objectives: We investigated the immune checkpoint inhibitors (ICPIs) therapeutic targets and specific T-regulatory and cytotoxic T-cell subsets in the subgroup of adolescent cHL patients, and we challenged their prognostic power.

Methods: We retrieved formalin-fixed paraffin-embedded (FFPE) tissue of adolescent patients diagnosed with cHL and tested by immunohistochemistry the immune checkpoint molecules CTLA-4, LAG-3, PD-1, and PDL1 as well as the biological markers FOXP3 and CD8.

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  • Plasma metabolomics analysis was conducted on 44 patients with relapsed/refractory B-cell non-Hodgkin lymphoma who were treated with CD19.CAR-T cell therapy, examining various time points before and after treatment.
  • At pre-lymphodepletion, a specific metabolic profile indicated poor outcomes, with high levels of lipoproteins and lactate linked to elevated lactate dehydrogenase.
  • By day 30, two patient clusters were identified: one group experienced long-term remission, while the other, with higher N-GlycA levels, was prone to relapse within a year, suggesting that pro-inflammatory shifts may be associated with relapse risk.
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A significant unmet need remains for patients with Hodgkin lymphoma (HL) who fail to respond to first-line treatment or experience an early relapse. Tinostamustine, a novel alkylating deacetylase inhibitor, inhibits tumor cell growth and slows disease progression in models of hematological malignancies and solid tumors. This was a Phase I, multicenter, open-label, two-stage trial investigating the safety and efficacy of tinostamustine in patients ≥ 18 years with relapsed/refractory (R/R) hematological malignancies, including HL.

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  • * The study focused on identifying brain-specific DNA methylation profiles to track brain-derived cfDNA (bcfDNA) through comparisons of brain and non-brain tissues and validated these findings on autopsy samples.
  • * The developed assay showed higher levels of bcfDNA in patients experiencing neurotoxicity after CAR-T therapy, indicating its potential for early detection of neuronal loss in neurodegenerative diseases.
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Purpose: Patients with relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL) generally have poor prognoses and limited treatment options. This study evaluated the efficacy of a novel CD30/CD16A bispecific innate cell engager, acimtamig (AFM13), in patients with R/R PTCL.

Patients And Methods: Patients included those with CD30 expression in ≥1% of tumor cells and who were R/R following ≥1 prior line of systemic therapy.

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What Is This Summary About?: This article provides a plain-language summary of the results of a clinical trial called the LOTIS-2 study.The LOTIS-2 study included 145 participants with an aggressive type (one that forms, grows, or spreads quickly) of non-Hodgkin lymphoma called diffuse large B-cell lymphoma (a type of blood cancer), or DLBCL for short, whose disease came back or did not respond after 2 or more previous treatments. The LOTIS-2 study was conducted from August 2018 to September 2022.

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  • Variations in access to drugs globally make it hard to assess the effectiveness of modern treatments for patients with relapsed and refractory mature T-cell and NK-cell lymphomas in a study of 925 patients.
  • * The study found that relapsed lymphoma patients had better overall survival rates compared to refractory patients after second-line treatment, with several factors identified as predictors of survival.
  • * A new prognostic index (PIRT) categorizes patients based on risk factors into low, intermediate, or high risk, impacting 3-year overall survival rates, and highlights the superior outcomes of novel therapies compared to traditional chemotherapy.
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Background: Peripheral T-cell lymphomas are aggressive non-Hodgkin lymphomas with few treatment options for relapsed or refractory disease. Valemetostat tosylate (valemetostat) is a potent, novel, dual inhibitor of EZH2 and EZH1. We investigated the clinical activity and safety of valemetostat in patients with relapsed or refractory peripheral T-cell lymphoma, and its safety in patients with relapsed or refractory adult T-cell leukaemia/lymphoma.

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Clinical bleeding events are reported here from 773 patients with B-cell malignancies receiving pirtobrutinib monotherapy from the phase 1/2 BRUIN study (ClinicalTrials.gov identifier: NCT03740529), either in the presence or absence of antithrombotic therapy (antithrombotic exposed [AT-E],  = 216; antithrombotic nonexposed [AT-NE],  = 557). Among the AT-E cohort, 51.

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Objective: We report patient-reported outcomes (PROs) measuring health-related quality of life (HRQoL) from the ROSEWOOD trial (NCT03332017), which demonstrated superior efficacy and a manageable safety profile with zanubrutinib plus obinutuzumab (ZO) versus obinutuzumab (O) in patients with heavily pretreated relapsed/refractory follicular lymphoma (R/R FL).

Methods: PROs were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) and EQ-5D-5L questionnaires at baseline and subsequently every 12 weeks. All QLQ-C30 domains and EQ-5D-5L visual analog scale (VAS) scores were analyzed descriptively.

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  • Bruton tyrosine kinase inhibitors (BTKi) have significantly improved treatment for B-cell malignancies, but many patients stop using them due to side effects, with cardiac issues being the most common reason for discontinuation.* -
  • The BRUIN study tested pirtobrutinib, a new non-covalent BTKi, on 127 patients who were intolerant to previous BTKi treatments, finding that many experienced fewer or no cardiac issues while showing a high overall response rate.* -
  • Results indicated pirtobrutinib had a median time on treatment of 15.3 months, with notable side effects like fatigue and neutropenia; overall, it proved to be a safe and effective alternative for
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  • * A panel of European physicians developed consensus statements to guide the prevention and treatment of DME, focusing on using glucarpidase and supportive measures like hyperhydration and urine alkalinization.
  • * Early identification of DME is crucial for timely interventions, which may include increased hydration, high-dose leucovorin, and glucarpidase when needed to mitigate risks associated with DME.
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First-line therapy for patients with extranodal marginal zone lymphoma (EMZL) is not well established, except for eradication therapy for Helicobacter pylori in early gastric MZL. Various regimens, for example, locoregional treatment and systemic chemo-immunotherapy, can be used depending on the site and stage of disease. Single-agent rituximab is a useful approach in the setting of localized, low-intermediate risk EMZL.

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  • The study investigates a chemotherapy-free treatment combining atezolizumab, venetoclax, and obinutuzumab for patients with diffuse large B-cell lymphoma variant of Richter transformation, which is known for being difficult to treat and having a poor prognosis.
  • It was a phase 2, multicenter trial involving 15 hospitals across Italy and Switzerland, targeting patients with a specific type of cancer transformation after certain prior conditions.
  • The primary goal was to achieve an overall response rate of at least 67% by day 21 of cycle 6, with the study being registered under ClinicalTrials.gov, NCT04082897, and completed by October 2022.*
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  • Follicular lymphoma (FL) is a slow-growing type of cancer that originates from a specific type of immune cell, and while treatment advancements have improved survival rates, it remains incurable, with risks of disease progression and treatment side effects for some patients.
  • The disease often recurs, and the effectiveness of treatments tends to decrease as patients undergo more therapy.
  • This review discusses current and emerging treatments for relapsed or refractory FL, emphasizing the need for personalized treatment strategies that weigh the risks, benefits, and specific preferences of each patient.
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Biomarkers for immune checkpoint inhibitors (ICIs) response and resistance include PD-L1 expression and other environmental factors, among which the gut microbiome (GM) is gaining increasing interest especially in lymphomas. To explore the potential role of GM in this clinical issue, feces of 30 relapsed/refractory lymphoma (Hodgkin and primary mediastinal B-cell lymphoma) patients undergoing ICIs were collected from start to end of treatment (EoT). GM was profiled through Illumina, that is, 16S rRNA sequencing, and subsequently processed through a bioinformatics pipeline.

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Copanlisib, a pan-class I phosphatidylinositol 3-kinase inhibitor with predominant activity against the α and δ isoforms, previously demonstrated durable responses as monotherapy and improved progression-free survival (PFS) in combination with rituximab in patients with relapsed indolent non-Hodgkin lymphoma (iNHL). CHRONOS-4 was a phase 3, randomized, double-blind, placebo-controlled study to investigate the efficacy and safety of copanlisib in combination with standard immunochemotherapy in patients with relapsed iNHL. Patients (n = 524) were randomized (1:1) to copanlisib (60 mg IV) plus immunochemotherapy (rituximab and bendamustine [R-B] or placebo plus R-B).

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BACKGROUNDPredicting immune effector cell-associated neurotoxicity syndrome (ICANS) in patients infused with CAR T cells is still a conundrum. This complication, thought to be consequent to CAR T cell activation, arises a few days after infusion, when circulating CAR T cells are scarce and specific CAR T cell-derived biomarkers are lacking.METHODSCAR+ extracellular vesicle (CAR+EV) release was assessed in human CD19.

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  • Pirtobrutinib is a new reversible drug that targets Bruton tyrosine kinase, showing effective results in treating B-cell malignancies with low patient dropout and dose reduction rates.
  • A study from the BRUIN trial evaluated the safety of pirtobrutinib in patients who were treated for 12 months or more, revealing common side effects like fatigue and diarrhea, with most adverse events occurring in the first year of treatment.
  • Overall, the findings suggest that pirtobrutinib has a favorable safety profile for long-term use, with no new significant toxicity concerns reported.
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Background: Adding ibrutinib to standard immunochemotherapy might improve outcomes and challenge autologous stem-cell transplantation (ASCT) in younger (aged 65 years or younger) mantle cell lymphoma patients. This trial aimed to investigate whether the addition of ibrutinib results in a superior clinical outcome compared with the pre-trial immunochemotherapy standard with ASCT or an ibrutinib-containing treatment without ASCT. We also investigated whether standard treatment with ASCT is superior to a treatment adding ibrutinib but without ASCT.

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