scholarly journals Mutations at Codon 641 of Exon 16 of EZH2 in Circulating Tumor DNA: A Biomarker for Relapse in Patients With Diffuse Large B-cell Lymphoma Treated With the R-CHOP Scheme.

2022 ◽  
Author(s):  
José Díaz-Chávez ◽  
Olga Gutiérrez-Hernández ◽  
Lucia Taja-Chayeb ◽  
Sindy Gutiérrez-Chavarría ◽  
Alejandro Aviles-Salas ◽  
...  
Keyword(s):  
B Cell ◽  
Sanger Sequencing ◽  
Prospective Trial ◽  
B Cell Lymphoma ◽  
Circulating Tumor Dna ◽  
Bivariate Analysis ◽  
Polycomb Repressive Complex 2 ◽  
Double Hit Lymphoma ◽  
A Subunit ◽  
The Impact

Abstract Background: The epigenetic regulator EZH2 is a subunit of the polycomb repressive complex 2 (PRC2), methylates H3K27, resulting in transcriptional silencing. The mutation at Y646 amino acid in the EZH2 gene is mutated in up to 40 % of B-cell lymphomas. Methods: We compared the presence of exon 16 EZH2 mutations in tumor samples and ctDNA in a prospective trial. The mutations were determined by sanger sequencing, and by ddPCR. We also evaluated the impact of these mutations on response, relapse, and survival. Results: One hundred and thirty-eight cases were included. Ninety-eight were germinal center, and twenty had EZH2 mutations. Mean follow-up (IQR 25-75) was 23 (7- 42) months. The tumor samples were considered the standard of reference. Considering the results of the mutation in ctDNA by Sanger sequencing, the sensibility (Se) and specificity (Sp) were 52 % and 99 %, respectively. After adding the ddPCR analysis, the Se and Sp increased to 95 and 100 %, respectively. After bivariate analysis, only the presence of double-hit lymphoma (p=0.04), or EZH2 mutations were associated with relapse. The median PFS (95 % Interval confidence) was 27.7 (95 % IC: 14-40) vs 44.1 (95 % IC: 40-47.6) months for the mutated vs wt patients. Conclusions: The ctDNA is usefull to analyse EZH2 mutations, which have an impact in PFS.

scholarly journals Impact of High-Dose Methotrexate on the Outcome of Patients with Diffuse Large B-Cell Lymphoma and Skeletal Involvement

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2945
Author(s):  
Mélanie Mercier ◽  
Corentin Orvain ◽  
Laurianne Drieu La Rochelle ◽  
Tony Marchand ◽  
Christopher Nunes Gomes ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Skeletal Involvement ◽  
Large B Cell Lymphoma ◽  
Dose Methotrexate ◽  
The Impact ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL) with extra nodal skeletal involvement is rare. It is currently unclear whether these lymphomas should be treated in the same manner as those without skeletal involvement. We retrospectively analyzed the impact of combining high-dose methotrexate (HD-MTX) with an anthracycline-based regimen and rituximab as first-line treatment in a cohort of 93 patients with DLBCL and skeletal involvement with long follow-up. Fifty patients (54%) received upfront HD-MTX for prophylaxis of CNS recurrence (high IPI score and/or epidural involvement) or because of skeletal involvement. After adjusting for age, ECOG, high LDH levels, and type of skeletal involvement, HD-MTX was associated with an improved PFS and OS (HR: 0.2, 95% CI: 0.1–0.3, p < 0.001 and HR: 0.1, 95% CI: 0.04–0.3, p < 0.001, respectively). Patients who received HD-MTX had significantly better 5-year PFS and OS (77% vs. 39%, p <0.001 and 83 vs. 58%, p < 0.001). Radiotherapy was associated with an improved 5-year PFS (74 vs. 48%, p = 0.02), whereas 5-year OS was not significantly different (79% vs. 66%, p = 0.09). A landmark analysis showed that autologous stem cell transplantation was not associated with improved PFS or OS. The combination of high-dose methotrexate and an anthracycline-based immunochemotherapy is associated with an improved outcome in patients with DLBCL and skeletal involvement and should be confirmed in prospective trials.

scholarly journals The impact of structural factors on diagnostic delay in diffuse large B‐cell lymphoma

2019 ◽  
Vol 8 (4) ◽  
pp. 1416-1422
Author(s):  
Joanna C. Zurko ◽  
Raymond C. Wade ◽  
Amitkumar Mehta
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Diagnostic Delay ◽  
B Cell Lymphoma ◽  
Structural Factors ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

scholarly journals How I treat double-hit lymphoma

Blood ◽  
2017 ◽  
Vol 130 (5) ◽  
pp. 590-596 ◽  
Author(s):  
Jonathan W. Friedberg
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Central Nervous System Involvement ◽  
B Cell Lymphoma ◽  
World Health ◽  
Large B Cell Lymphoma ◽  
Double Hit Lymphoma ◽  
Increased Risk ◽  
Double Hit ◽  
Large B Cell

Abstract The 2016 revision of the World Health Organization (WHO) classification for lymphoma has included a new category of lymphoma, separate from diffuse large B-cell lymphoma, termed high-grade B-cell lymphoma with translocations involving myc and bcl-2 or bcl-6. These lymphomas, which occur in <10% of cases of diffuse large B-cell lymphoma, have been referred to as double-hit lymphomas (or triple-hit lymphomas if all 3 rearrangements are present). It is important to differentiate these lymphomas from the larger group of double-expressor lymphomas, which have increased expression of MYC and BCL-2 and/or BCL-6 by immunohistochemistry, by using variable cutoff percentages to define positivity. Patients with double-hit lymphomas have a poor prognosis when treated with standard chemoimmunotherapy and have increased risk of central nervous system involvement and progression. Double-hit lymphomas may arise as a consequence of the transformation of the underlying indolent lymphoma. There are no published prospective trials in double-hit lymphoma, however retrospective studies strongly suggest that aggressive induction regimens may confer a superior outcome. In this article, I review my approach to the evaluation and treatment of double-hit lymphoma, with an eye toward future clinical trials incorporating rational targeted agents into the therapeutic armamentarium.

scholarly journals Diffuse large B-cell lymphoma mimicking chronic osteomyelitis of the ankle joint: A case report

2021 ◽  
Vol 9 ◽  
pp. 2050313X2098733
Author(s):  
Emam M Kheder ◽  
Hussain H Sharahlii ◽  
Saad M AlSubaie ◽  
Mushref A Algarni ◽  
Hussain Al Omar
Keyword(s):  
Case Report ◽  
B Cell ◽  
Ankle Joint ◽  
Chronic Osteomyelitis ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Chronic Infections ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Lymphoma is the seventh most common type of malignancy in both males and females. It may develop in any location where lymphomatous tissue exists. Although extranodal presentation in the lower limb and pelvis are uncommon, it could present with diverse manifestations. We report an unusual case of primary extranodal large B-cell lymphoma of the ankle joint initially presumed to be a chronic osteomyelitis. This case report discusses the impact of imaging studies on decision-making and highlights the need to consider malignancy in chronic infections.

U.S. budget impact analysis of biosimilar versus originator intravenous rituximab for the treatment of non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18820-e18820
Author(s):  
Elizabeth James ◽  
Holly Trautman ◽  
Ali McBride ◽  
Azhar Choudhry ◽  
Stephen Thompson
Keyword(s):  
B Cell ◽  
Impact Analysis ◽  
Budget Impact ◽  
Drug Acquisition ◽  
B Cell Lymphoma ◽  
Economic Benefits ◽  
Lymphocytic Leukemia ◽  
Sensitivity Analyses ◽  
Cost Share ◽  
The Impact

e18820 Background: Rituximab-abbs is an anti-CD20 monoclonal antibody and an important immuno-oncology agent for the treatment of B-cell malignancies NHL (diffuse large B-cell lymphoma [DLBCL] and follicular lymphoma [FL]) and CLL. It is also indicated for patients with RA, GPA, and MPA. Rituximab-abbs was the first rituximab biosimilar approved in the US and is expected to reduce drug acquisition costs. This budget impact model (BIM) estimated the impact of replacing a share of originator rituximab (IV-R-REF) use with rituximab-abbs (IV-R-BIOSIM) for NHL (DLBCL and FL), CLL, RA, GPA, and MPA. The objective was to project incremental annual cost differences between IV-R-BIOSIM and IV-R-REF for a hypothetical 1-million-member US healthcare insured (Medicare) population. Methods: An illustrative BIM estimated changes in 1-year drug and administration costs for an increased IV-R-BIOSIM uptake from 17.5% to 22.0%. Values for epidemiology, market share distribution, drug dosing, administration, and costs were derived from scientific literature, product labels, and publicly available cost resources. Dosing was based on a mean patient body surface area of 1.8 m2. Annual dose counts per patient were: 10 untreated FL with maintenance; 8 untreated FL (without maintenance), relapsed/refractory FL, or untreated DLBCL; 6 CLL, and 4 for RA, GPA, or MPA. All treatments were assumed to infuse over 3 hours. Drug acquisition and administration costs were from 2020 Average Sales Price pricing file and Centers for Medicare and Medicaid Services Physician Fee Schedule. Patient cost share was based on 2020 Medicare Part B 20% cost-share for office visits and drug products. Univariate sensitivity analyses were conducted. A scenario analysis was performed to project 2-year costs for extended FL maintenance treatment. Results: Estimated total annual plan incremental savings for a 1-million-member payer after the utilization shift were $312,379, equating to $0.31 per enrolled member per year (PMPY). Per-patient incremental drug cost savings with IV-R-BIOSIM for 1-year were $5,474–$12,924 (Table). The model was most sensitive to IV-R-REF cost and proportion of patients with RA. Conclusions: This analysis estimated annual savings of over $310,000 ($0.31 PMPY) for a 1-million-member US payer following a 4.5% utilization shift from IV-R-REF to IV-R-BIOSIM, demonstrating that IV-R-BIOSIM may confer considerable economic benefits vs originator rituximab.[Table: see text]

The Role of Transplantation in Diffuse Large B-Cell Lymphoma: The Impact of Rituximab Plus Chemotherapy in First-line and Relapsed Settings

2010 ◽  
Vol 6 (1) ◽  
pp. 47-57 ◽  
Author(s):  
Celso Arrais Rodrigues ◽  
Poliana Alves Patah ◽  
Yana A. S. Novis ◽  
Chitra Hosing ◽  
Marcos de Lima
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
First Line ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Inferior progression-free survival for Thai patients with diffuse large B-cell lymphoma treated under Universal Coverage Scheme: the impact of rituximab inaccessability

2012 ◽  
Vol 54 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Tanin Intragumtornchai ◽  
Udomsak Bunworasate ◽  
Noppadol Siritanaratkul ◽  
Archrob Khuhapinant ◽  
Weerasak Nawarawong ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Universal Coverage ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Universal Coverage Scheme ◽  
Large B Cell

scholarly journals Combination Treatment with GSK126 and Pomalidomide Induces B-Cell Differentiation in EZH2 Gain-of-Function Mutant Diffuse Large B-Cell Lymphoma

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2541
Author(s):  
Sungryul Park ◽  
Seung-Hyun Jo ◽  
Jong-Hwan Kim ◽  
Seon-Young Kim ◽  
Jae Du Ha ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cell ◽  
Zinc Finger ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
B Cell Differentiation ◽  
Gain Of Function ◽  
Polycomb Repressive Complex 2 ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), the catalytic subunit of polycomb repressive complex 2 (PRC2), regulates genes involved in cell lineage and differentiation through methylating lysine 27 on histone H3 (H3K27me3). Recurrent gain-of-function mutations of EZH2 have been identified in various cancer types, in particular, diffuse large B-cell lymphoma (DLBCL), through large-scale genome-wide association studies and EZH2 depletion or pharmacological inhibition has been shown to exert an antiproliferative effect on cancer cells, both in vitro and in vivo. In the current study, a combination of pomalidomide and GSK126 synergistically inhibited the growth of EZH2 gain-of-function mutant Diffuse large B-cell lymphoma (DLBCL) cells. Furthermore, this synergistic effect appeared to be dependent on cereblon (CRBN), a cellular receptor of pomalidomide, but not degradation of IKAROS family zinc finger 1 (IKZF1) or IKAROS family zinc finger 3 (IKZF3). RNA sequencing analyses revealed that co-treatment with GSK126 and pomalidomide induced specific gene sets involved in B-cell differentiation and apoptosis. Synergistic growth inhibition and B-cell differentiation were further validated in xenograft mouse models. Our collective results provide a molecular basis for the mechanisms underlying the combined therapeutic effects of PRC2 inhibitors and pomalidomide on EZH2-mutated DLBCL.

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