Association of PET4 Response With Outcomes of BV-CHP vs CHOP in the ECHELON-2 Trial in CD30+ Peripheral T-cell Lymphoma.

In the phase 3 ECHELON-2 trial, brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (BV-CHP) significantly improved progression-free survival (PFS) and overall survival (OS) compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in patients with CD30+ peripheral T-cell lymphoma (PTCL), benefits that were maintained at 5 years. Interim positron emission tomography (PET) scan can be used to assess prognosis and risk stratify patients. The prognostic value of interim PET was assessed in this post hoc exploratory analysis from ECHELON-2 evaluating interim 18F-FDG PET scans after cycle 4 (PET4) and end-of-treatment-based response and correlated with PFS per investigator and OS.

Brentuximab Vedotin addition to Gemcitabine in Relapsed or Refractory Peripheral T-cell Lymphoma: a LYSA Phase II Study.

We aim to evaluate the efficacy of brentuximab vedotin (BV) combined with gemcitabine followed by BV maintenance in relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL). Patients (pts) with at least 5% CD30-positive cells by immunohistochemistry received 4 GBV induction (28d) cycles of gemcitabine 1000 mg/m2 (d1;d15) plus BV 1.8 mg/kg (d8) followed in responding pts by up to 12 BV maintenance (21d) cycles.

IRF4 promotes immune evasion and shapes the tumor microenvironment in Follicular Lymphoma.

Twenty percent of follicular lymphoma (FL) patients relapse early with poor outcomes; however, the molecular mechanisms underlying this aggressive behavior are unknown. Using a multi-omics approach, we show that FL patients with elevated IRF4 expression (IRF4hi) have increased transformation risk, dysregulated immune signaling, and a suppressive tumor microenvironment. Loss- and gain-of-function experiments in IRF4hi lymphoma cells, along with chromatin profiling, demonstrate that IRF4 impairs their interaction with T cells by repressing antigen presentation and co-receptor gene modules, while promoting the expression of cytokines that antagonize TFH and Treg functions.

Lisocabtagene Maraleucel Versus Standard of Care for Second-Line Relapsed/Refractory Large B-Cell Lymphoma: 3-Year Follow-Up From the Randomized, Phase III TRANSFORM Study.

We report 3-year follow-up results from TRANSFORM comparing lisocabtagene maraleucel (liso-cel) versus standard of care (SOC) for second-line primary refractory/early relapsed (≤12 months) large B-cell lymphoma (LBCL). Adults eligible for autologous stem cell transplantation (N = 184) were randomly assigned 1:1 to liso-cel (100 × 10 chimeric antigen receptor-positive T cells) or SOC. Results are reported descriptively.

Combined PET and ctDNA response as a predictor of POD24 for follicular lymphoma after first-line induction treatment.

Patients with follicular lymphoma who experience disease progression within 24 months of diagnosis (POD24) have a lower survival. Positron emission tomography (PET) response and circulating tumor DNA (ctDNA) minimal residual disease (MRD) assessment at end of induction (EOI) may allow their early identification. A representative cohort of 141 patients from the RELEVANCE phase 3 trial with both available serum samples for ctDNA testing and PET images at randomization and at EOI (week 24) was investigated.

Investigating the Association Between a Continuous Variable and a Time-To-Event Outcome: Going Beyond the Cut-Off Approach.

When describing relationships between variables and an outcome, dichotomization of continuous variables remains a widely used approach in medical research despite many drawbacks: the loss of information which reduces the statistical power to detect an association, the risk of misclassification and the problem of comparability of the results. Alternative approaches based on flexible functions are available and would allow to use all the information contained in the data and thus to model the possible non-linear relation between the continuous variable and the outcome. But these alternative approaches are rarely used probably because of a lack of clear guidance.

Lymphoma B cells remodel bone marrow stromal cells into extracellular matrix-producing cancer-associated fibroblasts.

Bone marrow (BM) involvement is a common feature of germinal center-derived B-cell lymphomas and is associated with a poor prognosis. In particular, follicular lymphoma (FL) infiltrates the BM in 70% of cases, and analysis of in vitro-expanded FL BM mesenchymal stromal cells (MSCs) has revealed an extensive alteration of BM stromal cell phenotypic, transcriptomic, and functional profiles. However, the mechanisms underlying the direct interplay between lymphoma B cells and their permissive stromal niche in situ have not yet been identified.

Atezolizumab, obinutuzumab and venetoclax for the treatment of patients with relapsed/refractory B non-Hodgkin lymphoma: Final analysis of a phase II trial from the LYSA group.

Developing new therapeutic regimens for relapsed/refractory (R/R) B non-Hodgkin lymphoma (NHL) patients remains a significant unmet clinical need. Our objective was to evaluate atezolizumab (ATE), obinutuzumab (OBI) and venetoclax (VEN) combination in patients with R/R NHL who had received at least one prior anti-CD20-containing immunochemotherapy regimen. We report here the final analysis of the phase II LYSA-promoted multicentre trial (NCT03276468) of this combination in follicular lymphoma (FL, n = 58), diffuse large B-cell lymphoma (DLBCL, n = 58) and marginal zone lymphoma (MZL, n = 20).

Myeloid neoplasms after CD19-directed CAR T cells therapy in long-term B-cell lymphoma responders, a rising risk over time?

Therapy-related myeloid neoplasms (t-MN), including myelodysplastic neoplasms (t-MDS) and acute myeloid leukemia (t-AML), have emerged as significant late complications after CAR T cell therapy. We retrospectively analyzed 539 patients with B cell lymphoma treated with CD19 directed CAR T cell therapy across four French centers. Cumulative incidences of t-MN was estimated with relapse or death treated as competing risk.

Validation of POD24 as a robust early clinical indicator of poor survival in mantle cell lymphoma from 1280 patients on clinical trials, a LYSA study.

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 trials.

Glofitamab in refractory or relapsed diffuse large B cell lymphoma after failing CAR-T cell therapy: a phase 2 LYSA study.

Persons with diffuse large B cell lymphoma (DLBCL) refractory or in first progression/relapsed (R/R) after chimeric antigen receptor T (CAR-T) cell therapy exhibit dramatic outcomes. We enrolled such persons in a phase 2 single-arm, nonblinded trial ( NCT04703686 ) to evaluate the efficacy and safety of glofitamab, a CD20-CD3 T cell-engaging bispecific antibody, using a short ramp-up regimen to reach full dose within 1 week. A total of 46 participants received at least one glofitamab infusion following obinutuzumab (anti-CD20 monoclonal antibody) pretreatment.

Efficacy of tazemetostat in combination with R-CHOP in elderly patients newly diagnosed with diffuse large B cell lymphoma: results of the EpiRCHOP phase II study of the LYSA.

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 tazemetostat (800 mg BID), plus two cycles of tazemetostat and rituximab (cycles 7 and 8), from July 31, 2020 to July 18, 2022. Primary endpoint was positron emission tomography complete metabolic response (CMR).

Primary mediastinal B-cell lymphoma (PMBCL): The LYSA pragmatic guidelines.

Primary mediastinal B-cell lymphoma (PMBCL) is a distinct subtype of large B-cell lymphoma with unique clinical, histopathological, and molecular characteristics. Despite its aggressive nature, PMBCL has a high cure rate when managed appropriately. Advances in the understanding of PMBCL biological characteristics, coupled with improvements in diagnostic tools and therapeutic approaches, have significantly improved patient outcomes in recent years.

Prognostic impact of metabolic tumor volume using the SUV4.0 segmentation threshold in 1,960 lymphoma patients from prospective LYSA trials.

Purpose: This study compared the prognostic value of total metabolic tumor volume (TMTV) in lymphoma measured with the recently proposed SUV4.0 segmentation threshold versus the 41% SUVmax across LYSA trials and its impact on intensity and dissemination PET features.

Methods: A total of 1960 baseline PET/CT scans of Diffuse Large B cell lymphoma (DLBCL), follicular lymphoma (FL) and Hodgkin lymphoma (HL) patients were collected.

A low lymphocyte-to-monocyte ratio is independently associated with early relapse (POD24) in high tumour burden follicular lymphoma: A RELEVANCE subanalysis.

The peripheral blood lymphocyte-to-monocyte ratio (LMR) has been shown to predict outcomes in follicular lymphoma (FL). Among 1018 patients from the RELEVANCE trial (for previously untreated, high tumour burden FL), the median LMR was 2.5 (range, 0.

Interim PET after 4 cycles predicts outcome in histomolecularly confirmed primary mediastinal B-cell lymphoma.

The GAINED study was a randomized phase 3 trial comparing obinutuzumab (G) with rituximab (R) plus ACVBP (doxorubicin, cyclophosphamide, and prednisone, combined with either vindesine or bleomycin) or CHOP14 (cyclophosphamide, doxorubicin, vincristine, and prednisone, administered on a 14-day schedule) induction, followed by positron emission tomography (PET)-guided consolidation. This post hoc analysis aimed to detail the outcomes of patients with primary mediastinal B-cell lymphoma (PMBL), verified through expert pathological review and the use of gene expression profiling (GEP) and next-generation sequencing. Of 620 centrally reviewed patients, 138 (22.

Outcomes of patients with relapsed or refractory primary mediastinal B-cell lymphoma treated with anti-CD19 CAR-T cells: CARTHYM, a study from the French national DESCAR-T registry.

Primary mediastinal B-cell lymphoma (PMBL) is often cured with dose-dense anthracycline-based regimens but the prognosis at relapse or progression remains poor. While anti-CD19 CAR-T cell therapy has dramatically improved outcomes in relapsed or refractory large B-cell lymphoma, far less is known about their efficacy in PMBL. Using the systematic record of all patients treated with CAR-T cells prospectively included in the DESCAR-T registry in France, along with centrally reviewed positon-emission tomography (PET) imaging, we describe the outcomes and key determinants of treatment success in PMBL patients treated over a 6-year period.

Outcome of high-grade B-cell lymphoma compared with other large B-cell lymphoma after CAR-T rescue: a DESCAR-T LYSA study.

High-grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements (double hit [HGBL-DH] or triple hit [HGBL-TH]) or not otherwise specified (HGBL-NOS) are considered to be more aggressive diseases among large B-cell lymphomas (LBCLs). CD19-targeting chimeric antigen receptor (CAR) T cells have changed the prognosis of chemoresistant LBCL. Clinical and pathological data of patients treated for relapsed/refractory LBCL or HGBL in third line or more, all characterized by fluorescence in situ hybridization, were collected from the French DESCAR-T registry.

gneSeqCOO: a novel method for classifying diffuse large B-cell lymphoma cell of origin based on bulk tumor RNA sequencing profiles.

The cell of origin (COO) classification is an expression-based tumor algorithm identifying molecular subtypes of diffuse large B-cell lymphoma (DLBCL) with distinct prognostic characteristics. Traditional immunohistochemical methods for classifying COO subtypes have poor concordance and limited prognostic value in frontline DLBCL. In contrast, RNA-based metrics like the NanoString Lymphoma Subtyping Test (LST) define more robust subtypes with validated prognostic associations.

Safety and Efficacy of Tinostamustine in a Subpopulation of Patients With Relapsed/Refractory Hodgkin Lymphoma From a Phase I Trial.

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.

Building the future management of follicular lymphoma with T-cell-redirecting strategies.

Follicular lymphoma (FL) usually requires multiple lines of therapy, and disease control remains largely insufficient with conventional chemoimmunotherapy. Several T-cell-redirecting strategies recently approved in the relapsed/refractory setting have the potential to improve outcomes and change the treatment algorithm in FL. This review focuses on the role of chimeric antigen receptor T cells and bispecific antibodies in FL, paying special attention to sequencing approaches and future directions.

Classic Hodgkin Lymphoma: The LYSA pragmatic guidelines.

Classic Hodgkin lymphoma (HL) is a distinct entity among hematological malignancies of B-cell origin. It is characterized by its unique histopathological features and generally favorable prognosis. Over the years, advancements in understanding its pathogenesis, coupled with refined diagnostic and evaluation modalities, as well as therapeutic strategies, have significantly transformed the landscape of HL management.