Follicular Lymphoma Research Articles

Effect of POD24 on the prognosis of follicular and other indolent B-cell non-hodgkin lymphomas.

Indolent B-cell non-Hodgkin lymphomas(B-NHL) encompass a heterogeneous category of lymphomas characterized by a wide range of pathological subtypes. With the application of chemoimmunotherapy with rituximab (R-chemo), the prognosis of patients has improved considerably, with a 10-year survival rate of 60-80%. Despite these advancements, a significant number of patients still experience disease progression during or shortly after initial treatment. Those who progress within the first 24 months (POD24) continue to face a notably worse prognosis. This study aims to explore the significance of POD24 in predicting the prognosis of different subtypes of indolent B-cell NHL through a comprehensive literature review. The investigation extends to examining the existing prognostic assessment tools and evaluating the interrelationship between POD24 and these tools. By synthesizing relevant research findings, this study seeks to contribute to the current understanding of the role POD24 plays in prognostic evaluation and its potential implications in guiding clinical decision-making for patients with indolent B-cell NHL.

Follicular Lymphoma Presenting as a Primary Omental Mass: A Case Report and Pathological Analysis

Follicular Lymphoma Presenting as a Primary Omental Mass: A Case Report and Pathological Analysis

A case of lung adenocarcinoma and follicular lymphoma in the same lesion

A case of lung adenocarcinoma and follicular lymphoma in the same lesion

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.

A Complex Case of COVID-19 Pneumonitis in a Patient With Follicular Lymphoma

A Complex Case of COVID-19 Pneumonitis in a Patient With Follicular Lymphoma

FoxO1 signaling in B cell malignancies and its therapeutic targeting.

FoxO transcription factors (FoxO1, FoxO3a, FoxO4, FoxO6) are a highly evolutionary conserved subfamily of the 'forkhead' box proteins. They have traditionally been considered tumor suppressors, but FoxO1 also exhibits oncogenic properties. The complex nature of FoxO1 is illustrated by its various roles in B cell development and differentiation, immunoglobulin gene rearrangement and cell-surface B cell receptor (BCR) structure, DNA damage control, cell cycle regulation, and germinal center reaction. FoxO1 is tightly regulated at a transcriptional (STAT3, HEB, EBF, FoxOs) and post-transcriptional level (Akt, AMPK, CDK2, GSK3, IKKs, JNK, MAPK/Erk, SGK1, miRNA). In B cell malignancies, recurrent FoxO1 activating mutations (S22/T24) and aberrant nuclear export and activity have been described, underscoring the potential of its therapeutic inhibition. Here, we review FoxO1's roles across B cell and myeloid malignancies, namely acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt lymphoma (BL), Hodgkin lymphoma (HL), and multiple myeloma (MM). We also discuss preclinical evidence for FoxO1 targeting by currently available inhibitors (AS1708727, AS1842856, cpd10).

Intestinal follicular lymphoma, an atypical entity with typical endoscopic presentation.

The most common extranodal localization of lymphomas is the small intestine, with large B-cell lymphoma and MALT lymphoma being the most typical types. Intestinal follicular lymphomas are an infrequent entity; however, due to improved endoscopic definition, diagnosis is more ando more common. We present the case of a 56-year-old woman diagnosed with follicular lymphoma, an entity that, although infrequent, has a typical endoscopic appearance. Recognition of the features described in this article may help to guide the diagnosis of this entity, which, on most occasions, has an indolent clinical course.

Impact of the WHO-5 classification of haematolymphoid tumours on clinical practice

SummaryThe long-awaited 2022 World Health Organization Classification of Haematolymphoid Tumours (WHO-5-HAEM) has finally been published as part of the IARC Blue Book series. This two-volume edition is significantly more comprehensive than its predecessors, reflecting the integration of extensive advancements in genetic and molecular understanding, alongside clinically relevant findings. This brief review will highlight the key changes in the classification of the most common B‑cell lymphoproliferative disorders, specifically follicular lymphomas and large B‑cell lymphomas (LBCL). It will also introduce new entities and summarize the most critical updates within these lymphoma categories.

Changes of T cell subsets across treatments associated with prognosis in newly diagnosed follicular lymphoma.

Follicular lymphoma (FL) is an immune-responsive tumor with spontaneous remission. T cells play a pivotal role in the anti-lymphoma immune response. However, the dynamics of T cells during treatment, their impact on FL clinical outcomes, and the risk factors contributing to T-cell cytopenia remain largely unexplored. T-cell and their subsets in the peripheral blood of FL patients at diagnosis, during 2-4 cycles and after 6 cycles of treatment, as well as healthy individuals were detected by flow-cytometry. The predictive effects of T cells for early progression and risks for T-cell cytopenia were analyzed. FL patients exhibited a significant decrease in CD3+, CD4+, and CD8 + T cells compared to healthy individuals, with aging intensifying the decline of CD3+, and CD4 + T cells. Notably, a reduction in CD4 + T cells, predominantly contributing to treatment-related T-cell reduction, was only observed in patients undergoing Bendamustine-based regimens. Moreover, a significantly decreased CD4 + and CD8 + T-cell at diagnosis rather than after induction therapy was observed in patients with treatment failure. Furthermore, lower CD4 + T-cell (< 260/uL) at baseline was independently correlated to early progression within 24 months. Finally, disease stage and albumin were the independent predictive factors for the decline of CD4 + T cells in FL patients. Overall, FL patients demonstrated compromised T-cell immunity, with a lower CD4 + T cell count at diagnosis correlating with treatment response and early progression. Therefore, monitoring CD4 + T cells at diagnosis might reflect immune status and aid in stratifying FL patients.

BIOM-09. CLINICAL EFFECT OF CD25 ON THE MTX-BASED CHEMOSENSITIVITY OF PRIMARY CENTRAL NERVUS SYSTEM LYMPHOMA

Abstract INTRODUCTION Primary central nervous system diffuse large B-cell lymphoma (PCNSL) is treated with chemotherapy, mainly with high-dose methotrexate (HD-MTX), but some cases are resistant to treatment and relapse in a short period. However, a biomarker that predicts the chemosensitivity and recurrence has not yet been identified. In this study, we used surface marker analysis of tumor tissue using flow cytometry to search for biomarkers related to chemosensitivity and early recurrence. METHODS From 2017 to 2023, 25 patients were diagnosed with PCNSL by biopsy in Kobe University Hospital, and flow cytometry of the biopsy tissues were performed. Cerebrospinal fluid (CSF) examination including sIL2R, β2MG, and IL-10 was performed in all cases before surgery, and treatment based on methotrexate was administered postoperatively. We retrospectively analyzed patient characteristics, flow cytometry data, treatment details, response rate, time to recurrence, and overall survival. RESULTS The mean age of the patients was 71 (range, 37-80) years. In univariate analysis, high expression level of CD25 (interleukin-2 receptor, IL-2R) in the tissue was associated with a lower response rate to MTX-based chemotherapy (Fisher’s exact test, p=0.0072) and had a tendency of shorter time to recurrence. However, there were no significant differences in progression-free survival and overall survival. There was no correlation between expression level of CD25 in tissue and sIL-2R in CSF. Expression level of sIL-2R in CSF was independent of CD25 expression in tissue. CONCLUSION There are some reports that CD25 can be a prognostic factor in follicular lymphoma, but no reports in PCNSL. Here, we suggested that high expression level of CD25 in PCNSL tissue was associated to chemoresistance and early recurrence. In cases of PCNSL with high CD25 expression level, additional whole-brain irradiation and transition to tirabrutinib be considered because there are possibilities of chemoresistance and early recurrence.

Follicular Lymphoma Diagnosed Successfully via Endobronchial Ultrasound-Guided Intranodal Forceps Biopsy Located in Left Lymph Node #12

Follicular Lymphoma Diagnosed Successfully via Endobronchial Ultrasound-Guided Intranodal Forceps Biopsy Located in Left Lymph Node #12

CaClust: linking genotype to transcriptional heterogeneity of follicular lymphoma using BCR and exomic variants.

Tumours exhibit high genotypic and transcriptional heterogeneity. Both affect cancer progression and treatment, but have been predominantly studied separately in follicular lymphoma. To comprehensively investigate the evolution and genotype-to-phenotype maps in follicular lymphoma, we introduce CaClust, a probabilistic graphical model integrating deep whole exome, single-cell RNA and B-cell receptor sequencing data to infer clone genotypes, cell-to-clone mapping, and single-cell genotyping. CaClust outperforms a state-of-the-art model on simulated and patient data. In-depth analyses of single cells from four samples showcase effects of driver mutations, follicular lymphoma evolution, possible therapeutic targets, and single-cell genotyping that agrees with an independent targeted resequencing experiment.

Tumour assessment of ROR1 levels in various adult leukaemia and lymphoma types.

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a tumour target currently used for the development of novel therapeutic modalities, such as antibody-drug conjugates, chimeric antigen receptor T-cell therapies, and others. Success of these new drugs depends on the selection of relevant indications based on ROR1 tumour prevalence, staining heterogeneity, and subcellular localization, among other parameters. We investigated ROR1 immunophenotype using validated antibody clones for immunohistochemistry (IHC) and flow cytometry (FC), analyzing 292 tumour specimens from 7 haematological malignancies and triple negative breast cancer (TNBC) as a reference solid tumour indication. ROR1 prevalence varied significantly across distinct tumour types, showing 100% of ROR1 positivity in all chronic lymphocytic leukaemia (n = 48) and hairy cell leukaemia (n = 14) specimens analyzed via FC with ranges between 1.1-99.8% and 0.8-62.1%, respectively. Samples analysed via IHC showed ROR1 membrane/cytoplasmic positivity in 44% of mantle cell lymphoma tumour samples (n = 27; H-score range: 10-285 in positive cases); 30% in TNBC (n = 46; H-score range: 1-200); 15% in diffuse large B-cell lymphoma (n = 45; H-score: 40-250); and 11% in follicular lymphoma (n = 34; H-score: 2-300). Finally, all acute myeloid leukaemia (n = 52) and most T-cell non-Hodgkin lymphoma (n = 31/32) tested samples were negative for ROR1 via IHC. In conclusion, ROR1 shows a heterogeneous tumour cell expression profile across multiple leukaemias and lymphomas, making it a tumour target that would require different patient selection strategies to develop novel therapeutic modalities.

Recent developments in marginal zone lymphoma

SummaryMarginal zone lymphoma is a relatively rare disease with a usually indolent clinical course. In clinical terms, three major subtypes—i.e., extranodal, nodal, and splenic marginal zone lymphomas—are encountered, which have specific clinical features. Clinical progress, however, has been limited in recent years as they are mostly lumped together with follicular lymphoma under the term “indolent lymphomas” in clinical trials. A talk given at the 2024 Annual Meeting of the Austrian Society of Hematology and Oncology aimed to summarize clinically relevant topics and progress in the field of marginal zone lymphoma, which is summarized in the current article.

The causal relationship between anti-CD20 antibodies and endometrial cancer: a Mendelian randomization study

PurposeTo determine the effects of anti-B cell surface marker CD20 antibody on the occurrence and progression of endometrial cancer to provide insights into clinical treatment in the future.MethodsWe performed a two-sample Mendelian randomization analysis (MR) to analyze the causal relationship between EC and immune cell markers. The genome-wide association study (GWAS) data of MS4A1 single nucleotide polymorphism encoding gene of CD20 were collected, and a drug target MR analysis was performed to detect the causal relationship between anti-CD20 antibody and the risk of EC. The risk of follicular lymphoma was used as a positive control, and EC was used as the outcome.ResultsEC exerted an effect on 28 immunophenotypes, predominantly on CD20. CD20 in immunoglobulin D+ CD38− B cells, memory B cells, and unsw memory B cells increased after EC onset. In addition, we detected one immunophenotype that exerted a dangerous effect on EC, i.e., CD3/TD CD4+ (mature stage of the T cell group). Simultaneously, CD20 could be used as both a risk factor and a protective factor for EC (P > 0.05). Anti-CD20 antibodies significantly reduced the risk of follicular lymphoma, including two GWAS pooled datasets. In addition, anti-CD20 antibodies exerted a protective effect on EC in two GWAS pooled datasets (P > 0.05).ConclusionOur study confirms the close relationship between CD20 and EC. Anti-CD20 antibodies may exert a protective effect on EC and reduce the risk of EC morbidity, providing a reference for future clinical diagnosis and treatment. However, further clinical verification of our results is warranted.

Safety in Subsequent Lines of Therapy in Patients With Relapsed Refractory Follicular Lymphoma

Follicular lymphoma (FL) is a disease often characterized by chronic and successive relapses after first-line chemoimmunotherapy. Although chemoimmunotherapy and combination therapy, such as lenalidomide with rituximab, are well established in the treatment sequence of FL, there is a need to streamline treatment options and determine placement of novel agents, such as chimeric antigen receptor T-cell therapy, an enhancer of zeste homolog 2 inhibitor, or a phosphoinositide 3 kinase inhibitor, into the treatment landscape. As such, the purpose of this review is to compare the safety profiles of approved agents in subsequent lines of therapy for relapsed or refractory FL and to assess how the management of adverse events may impact treatment choice.

Bilan initial, facteurs pronostiques et évaluation de la réponse thérapeutique des lymphomes

Over the past two decades, FDG-PET has transformed the management of lymphomas, significantly enhancing staging and prognostic assessment, particularly with the adoption of the Lugano recommendations (2014). Now widely used for Hodgkin's lymphoma, DLBCL, and other FDG-avid lymphomas, PET has largely replaced the need for routine bone marrow biopsies. Intermediate PET (iPET) has proven to be a valuable tool for predicting outcomes, playing a crucial role in guiding patient stratification and treatment modifications, especially in Hodgkin's lymphoma and DLBCL. However, its early use in other types of lymphoma still requires further clinical validation. For follicular and mantle cell lymphomas, PET has shown promise in assessing treatment response, although the criteria for evaluating response need to be optimized. PET's integration into personalized treatment strategies enables more effective disease control while minimizing treatment-related toxicity.

Bispecific antibodies in follicular lymphoma.

Bispecific antibodies, specifically anti-CD20 T-cell engaging constructs, are poised to alter the treatment paradigm of multiple B-cell malignancies, including follicular lymphoma. Two CD20xCD3 bispecific antibodies, mosunetuzumab and epcoritamab, are now approved in the United States for third-line or later treatment of follicular lymphoma. A third agent, odronextamab, remains under review by regulatory agencies. In pivotal phase II trials, these bispecific antibodies demonstrated overall response rates of approximately 80%, with complete response rates of 60-70%, the majority of which have been durable at two years. Important safety signals included risk of infections, neutropenia, and cytokine release syndrome, which occurred in approximately half of patients, but was rarely high grade. Despite similar efficacy and toxicity profiles, key differences exist among agents, primarily relating to treatment duration, route of administration, and prophylactic corticosteroid use. Several ongoing studies are exploring bispecific antibodies in earlier lines of treatment, either as single agents or in combination with other active therapies. This novel class of agents is likely to play a pivotal role in improving outcomes for patients with follicular lymphoma.

Follicular lymphoma research: an open dialogue for a collaborative roadmap.

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 progress since the advent of the immunotherapy era more than 20 years ago, much remains to be done to understand and cure this lymphoma. Today, FL is metaphorically a giant puzzle on the table with patches of sky, landscape and foliage clearly appearing. However, many of the remaining pieces are held by various stakeholders (e.g. clinicians, pathologists, researchers, drug developers) without global agreement on what the gaps are, or any clear blueprint on how to solve the puzzle of understanding the heterogeneity of this disease and create curative and tailored therapies. With the advent of new investigation and drug technologies, together with recent advances in our capacity to manage big data, the time seems ripe for a change of scale. More than ever, this will require collaboration between and within all stakeholders to overcome the current bottlenecks in the field. As for every investigator, we acknowledge that this first draft is necessarily biased, incomplete and some FL expert readers might recognise some remaining gaps not addressed. We hope they will reply to make this effort a collaborative one to assemble all the pieces in the most ideal fashion. As such, this review intends to be a first step and an interactive platform to a collaborative roadmap towards better understanding and care of FL.

Comparative Analysis of Bispecific Antibodies and CAR T-Cell Therapy in Follicular Lymphoma.

The treatment landscape for relapsed/refractory follicular lymphoma (RR-FL) is marked by a pivotal debate between chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAbs). While both CAR-T therapy and BsAbs target similar immunobiology and molecular markers, their efficacy comparisons are hindered by the lack of direct clinical trial comparisons. Key trials, such as the ZUMA-5 study, underscore axicabtagene ciloleucel (axi-cel)'s efficacy in treating RR-FL, achieving a 79% complete response rate with a median duration of response exceeding 3 years. Similarly, lisocabtagene maraleucel (liso-cel) in the TRANSCEND FL study reports a 94% complete response rate, emphasizing robust outcomes in heavily pretreated patients. Among BsAbs, mosunetuzumab showed promise in the GO29781 trial, with a 62% overall response rate in heavily pretreated RR-FL patients. Thus, CAR-T therapy offers potential curative benefits with a single infusion. However, its efficacy is tempered by significant adverse events such as cytokine release syndrome (CRS), neurotoxicity, and cytopenias, requiring specialized management and patient monitoring. In contrast, BsAbs provide a more tolerable treatment option counterbalancing by lower response rates and frequent dosing requirements. Personalized treatment strategies are crucial because of these distinct efficacy and safety profiles. When considering cost-effectiveness, both therapies need to be evaluated in the context of their clinical outcomes and quality of life improvements. Cost-effectiveness considerations are essential; while CAR-T therapies incur higher initial costs, their potential for long-term remission may mitigate expenses associated with repeated treatments or hospitalizations. Future research into resistance mechanisms and optimal therapeutic sequencing will further refine RR-FL management strategies.