Fostamatinib for the treatment of diffuse large B-cell lymphoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20067-e20067
Author(s):  
Hendrik-Tobias Arkenau ◽  
Anna Patrikidou ◽  
Ian Flinn ◽  
Jonas C. Hylton ◽  
Sandra Tong ◽  
...  
Keyword(s):  
Partial Response ◽  
B Cell ◽  
Clinical Benefit ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Intermediate Cell ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Large B Cell

e20067 Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive and common form of non-Hodgkin’s lymphoma, characterized by marked genetic heterogeneity. The disease is difficult to treat, and patients with relapsed/refractory DLBCL often have poor outcomes. Some subsets of DLBCL have an increased reliance on B-cell receptor (BCR) activity. Spleen tyrosine kinase (SYK) is a signaling molecule essential for BCR activation. Fostamatinib, an oral SYK inhibitor, was evaluated for treatment of relapsed/refractory DLBCL in a phase 2 randomized, placebo-controlled trial1(NCT01499303), and 9 patients had clinical benefit (1 complete response, 1 partial response, and 7 stable disease). The patients with clinical benefit from fostamatinib treatment had DLBCL of germinal center B-cell (GCB) or intermediate cell of origin. We present the clinical outcomes of 2 patients from this trial who continued to benefit from fostamatinib treatment for over 6 years. Methods: Medical records for the 2 patients were retrospectively reviewed for dose regimen, clinical response, and safety data. Results: Patient A, a 63-year-old male patient with DLBCL of GCB origin, had been diagnosed with follicular lymphoma in 1996, transformation in 2002. He had undergone 1 line of treatment for follicular lymphoma and 5 treatments for DLBCL prior to fostamatinib treatment. He started fostamatinib at 100mg BID in Dec 2012, which was reduced to 100mg daily in Apr 2013, and patient continues at 100 mg QD. Patient A has maintained a complete response (CR) for > 5 years. An isolated infra-centimetric suspicious lesion was noted in Patient A in May 2019, which is stable as of January 2020 with a progressive decrease of metabolic activity. Patient B, a male with DLBCL of an intermediate cell of origin, was 69 years old at baseline with 2 DLBCL treatments prior to fostamatinib treatment since his diagnosis in Aug 2012. He started fostamatinib in May 2013 at 200 mg BID with no dose changes over the last 7 years. Patient B had a partial response (PR) per Chesson criteria since December 2014, with a sustained improved metabolic response continuing since ( > 6 years), with all but a single metastatic site no longer visible. The only serious adverse event in these 2 patients was a ventricular fibrillation and grade 4 cardiac arrest at Day 90 in Patient B, necessitating defibrillation insertion. This was deemed unrelated to treatment and resolved. Conclusions: Fostamatinib may provide durable benefit to a small subset of patients with relapsed/refractory DLBCL. 1. Flinn, I.W., et al., Eur J. Cancer 2016; 54:11-17

scholarly journals A multi-institutional analysis of diffuse large B-cell lymphoma (DLBCL) treated with consolidative radiotherapy and the impact of cell-of-origin on outcomes

2019 ◽  
Vol 53 (4) ◽  
pp. 473-479 ◽  
Author(s):  
Chrishanthi Rajasooriyar ◽  
Jeremy Tey ◽  
Lea Choung Wong ◽  
Michelle Poon ◽  
Rao Nandini ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Disease Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Cell Of Origin ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Abstract Background Patients with diffuse large B-cell lymphoma (DLBCL) with bulky disease and/or those who fail to achieve complete response benefit from the addition of radiotherapy (RT). We aim to review the outcome, as well as determine the impact of cell-of-origin, on patients undergoing consolidative RT. Patients and methods Patients with DLBCL treated with radical intent consolidative RT were included. Clinical, pathological and treatment characteristics were extracted from electronic medical records. Survival outcomes and factors that predict for disease-free survival (DFS) were analysed. Results Seventy-four patients were included in this analysis. The median follow up was 3 years (0.7–16 years). Fifty-eight percent of patients had stage I–II disease, and 61% received at least 6 cycles of chemotherapy. Cell-of-origin was discernible in 60% of patients, and approximately half were classified as Germinal centre origin. The 5-year overall survival (OS) of this group was excellent at 92% (median survival not reached). The 5-year DFS was 73% (95% CI 57–83%). Seven percent (n = 5) of patients experienced local recurrence at a median time of 6 months. Failure to achieve complete response post RT and/or initial bulky disease are significant predictors of inferior DFS. There was no association between cell-of-origin and DFS or OS. Conclusions The outcome of patients who received radiotherapy as consolidation is excellent. Patients who fail to achieve complete response after radiotherapy had poorer outcomes. Despite using radiotherapy, presence of bulky disease remains a significant predictor of disease recurrence. We did not find any association of poorer outcomes, with regards to cell-of-origin, in the use of consolidative RT.

scholarly journals Comparison of R-CHOP with CHOP in Patients of Diffuse Large B Cell Lymphoma

Esculapio ◽  
2021 ◽  
Vol 16 (4 (oct 2020 - dec 2020)) ◽  
Author(s):  
Faiza Rehman Lodhi ◽  
Amjad Zafar ◽  
Muhammad Abbas Khokhar ◽  
Ali Waheed Goraya ◽  
Sobia Yaqub
Keyword(s):  
Partial Response ◽  
B Cell ◽  
Progressive Disease ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Large B Cell Lymphoma ◽  
Group I ◽  
Group Ii ◽  
Large B Cell

Objective: Diffuse large B cell lymphoma (DLBCL) is a lymphoid B cells neoplasm with a diffuse pattern and high proliferation rate. Cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) was considered effective as other complicated regimens with more toxicity profile. Rituximab is a monoclonal antibody directed against CD20 positive B cell. It has good activity therapeutically in patients of DLBCL. It increases response rates and survivals when added to CHOP chemotherapy. Although R-CHOP is more effective but due to high cost of Rituximab it is usually not incorporated with chemotherapy in most of our patients and CHOP is still used extensively. Due to heterogeneity of disease and difference in ethnicity, there may be difference in outcomes of two regimens. This study will help us in tailoring our management plan that will result in better outcome of patients. Methods: 70 patients aged between 20-65 years having DLBCL were taken in this study. We rando-mized patients by lottery method into two groups. Group I received CHOP with dose of Cyclophosphamide 750mg/m2, Doxorubicin 50mg/m2, Vincristine 1.4 mg/m2 and prednisolone 40mg/m2.Chemotherapy was given on Day-1 while prednisolone was given for 5 days from Day-1 of chemotherapy. Group II received R- CHOP which includes same chemotherapy with same dosage. Rituximab was included in Group II with dose of Rituximab 375 mg /m2. Each cycle was given at three weeks interval. Response in terms of CR (Complete Response), PR (Partial Response), SD (Stable Disease) or PD (Progressive Disease) was evaluated as per leukemia network after 4 cycles of chemotherapy. The quantitative variables were calculated by taking mean and standard deviation. The response was assessed in percentage and frequencies and compared by applying chi square test. Results: Group I had 37.1% while Group II had 68.6% complete response with p value of 0.019. Partial response was 48.6% in Group I while 20.0% in Group II. 14.3% in Group I and 8.6% in Group II either had stable disease or progressive disease. Conclusions: R-CHOP has superior response rates as compared to CHOP, therefore, whenever possible Rituximab should be added as target therapy in chemotherapy. Key Words: Diffuse large B cell lymphoma, CHOP, R- CHOP How to Cite: Lodhi F.R, Zafar A, Khokhar M.A, Goraya AW, Ashraf S, Yaqub S. Comparison of R-CHOP with CHOP in patients of diffuse large B cell lymphoma. Esculapio.2020;16(04):79-82.

scholarly journals Triple-negative diffuse large B-cell lymphoma: A distinct entity

2021 ◽  
Vol 12 (4) ◽  
pp. 427-429
Author(s):  
Yasmine Slimani ◽  
Fouzia Hali ◽  
Fatima-Zohra El Fatoiki
Keyword(s):  
B Cell ◽  
Triple Negative ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Positive Staining ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Large B Cell

The Hans algorithm categorizes the diffuse large B-cell lymphoma (DLBCL) into two major subtypes: the germinal center B-cell-like (GCB) DLBCL and the non-GCB DLBCL. This classification is based on three immunohistochemical markers: CD10, BCL6, and MUM1. The non-GCB subtype is associated with lower overall survival (OS) and progression-free survival (PFS) rates compared to the GCB. DLBCL without positive staining for these three markers (CD10–, BCL6–, MUM1–), also called a triple negative or TN, are classified as the non-GCB subtype. However, they show different clinical characteristics and better prognosis than others assigned to the same cell-of-origin group. Herein, we report a case of a TN non-GCB DLBCL with a complete response after R-CHOP therapy. Together with previous reports of TN non-GCB DLBCLs, our case might depreciate the prognostic value of the Hans algorithm, which was already controversial in the literature, especially in the chemoimmunotherapy era.

DIFFUSE LARGE B-CELL LYMPHOMA SURVIVAL PROGNOSTICATION, A COMPARATIVE ANALYSIS OF CELL OF ORIGIN VS. MYC/BCL2 EXPRESSION

2019 ◽  
Vol 37 ◽  
pp. 353-353
Author(s):  
M. Rodriguez ◽  
I. Fernandez-Miranda ◽  
R. Mondejar ◽  
J. Capote ◽  
S. Rodriguez-Pinilla ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Bcl2 Expression

scholarly journals Impact of Genetic Polymorphism of Myeloid Differentiation Primary Response Gene 88, Enhancer of Zeste Homolog 2, and B-cell Lymphoma 2 like 11 in Patients with Diffuse Large B Cell Lymphoma Treated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristin

2021 ◽  
Vol 9 (A) ◽  
pp. 98-105
Author(s):  
Hussam Zawam ◽  
Noha E. Ibrahim ◽  
Rasha Salama ◽  
Mai Samir ◽  
Walaa Abdelfattah ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Poor Response ◽  
Cell Of Origin ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Younger Age ◽  
Extranodal Disease ◽  
Large B Cell

BACKGROUND: Despite the growing landscape of genetic drivers in Diffuse Large B-cell Lymphoma, yet their clinical implication is still unclear and R-CHOP regimen remains a “one size fits all” therapy. We aimed in this study to examine the prevalence of EZH2, BCL211 and MYD 88 genetic polymorphisms in DLBCL patients and correlate the results with various clinical and survival outcomes. METHODS: Genotyping of MYD88 (rs387907272 T/C), EZH2 (rs3757441 C/T), and BCL2L11 (rs3789068 A/G) polymorphisms were conducted using real time polymerase chain reaction analysis in a total of 75 DLBCL patients. RESULTS: Most of our cases carried the wild TT genotype of MYD88 gene (64%), the mutant TT genotype of EZH2 gene (52%) and the wild AA genotype of BCL2L11 gene (48%). Regarding cell of origin, Germinal Centre (GC) phenotype was present in 56% of cases while 44% expressed the Post-GC (PGC) phenotype. Poor response outcome to first line R-CHOP was significantly correlated with the mutated CC genotype of MYD 88 (p=0.02), while better response to R-CHOP was significantly associated with younger age <50 years (p <0.0001), good PS (p=0.046), normal LDH level (p=0.003), earlier stage (p <0.0001), good IPI score (p=0.009), absence of extranodal disease (p <0.0001) and absence of bulky disease (p=0.004). The median PFS and the 2 year OS were significantly higher in younger age, earlier stage, good IPI score, absence of extranodal disease, absence of bulky disease and in GC phenotype. CONCLUSIONS: Our results emphasized that the mutated genotype of MYD 88 gene polymorphism is significantly associated with poor response to R-CHOP therapy.

scholarly journals Identification and Reporting of Cell of Origin, Double-/Triple-Hit and Double Expressor Lymphoma in a Real-World Cohort of Diffuse Large B-Cell Lymphoma Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-29
Author(s):  
Fei Yang ◽  
Anup Abraham ◽  
Ju Zhang ◽  
Yan Xiao ◽  
Richard D. Hammer ◽  
...  
Keyword(s):  
B Cell ◽  
Real World ◽  
Cell Lymphoma ◽  
Karyotype Analysis ◽  
Diagnostic Testing ◽  
Healthcare Providers ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Background The distinction of diffuse large B-cell lymphoma (DLBCL) into cell-of-origin (COO) subgroups (germinal center B-cell-like [GCB] or activated B-cell-like [ABC]) based on gene expression profiling is associated with prognosis and has potential therapeutic implications to mitigate the worse outcome for patients with DLBCL. Other phenotypic and molecular/cytogenetic features such as concurrent translocations of oncogene MYC and BCL2 and/or BCL6 (so-called double-/triple-hit lymphoma, DHL/THL) and coexpression of MYC and BCL2 proteins (so-called double-expressor lymphoma, DEL) are also recognized to have great prognostic impact (Swerdlow SH et al. Blood 2016;127(20):2375-2390). This study investigated the prevalence of COO, DHL/THL and DEL in a real-world cohort of patients with DLBCL who had documented results of diagnostic testing. Methods This study used the Flatiron Health electronic health record-derived de-identified database to abstract information on patients diagnosed with DLBCL between 2011-2019. Information on diagnostic testing from immunohistochemistry (IHC) for expression of MYC, BCL2, BCL6, CD10 or MUM1, and from fluorescence in situ hybridization (FISH) or karyotype analysis for rearrangement of MYC, BCL2 or BCL6 was abstracted from pathology reports or clinical visit notes, where available. We calculated the proportions of COO subgroups (GCB vs. ABC) that were derived from IHC testing results according to Hans algorithm (Hans C et al., Blood 2004;103(1):275-282), DHL/THL, and DEL. We also examined concordance of COO classification derived from IHC testing results with that directly reported by the healthcare providers. Differences in patient characteristics between IHC testing results-derived COO subgroups (GCB vs. ABC) were assessed using chi-square tests. Results 4400 patients had documented results of IHC and 73% (n=3194) can be classified into either GCB or ABC DLBCL (GCB/ABC ratio of 1.38). 3205 patients had documented results of FISH or karyotype analysis and 8% (n=245) were DHL/THL; only 33 patients were DEL. Within the GCB DLBCL patients derived from IHC testing results (n=1854), 163 patients were DHL/THL and 11 were DEL, whereas 24 DHL/THL and 18 DEL were identified within the ABC type (n=1340). When comparing COO classification derived from IHC testing results (n=3194) with that directly reported by the healthcare providers (n=2765), additional 695 and 439 patients can be classified as GCB and ABC DLBCL by IHC, respectively (Table). Univariate analysis showed that patients who were non-White ethnic group, diagnosed in academic centers, with lower body mass index but elevated serum lactate dehydrogenase levels and worse ECOG performance status, and without transformation from a prior indolent lymphoid malignancy, were more likely to be associated with ABC DLBCL (for all variables, p&lt;0.05). There were no clinically meaningful and/or statistically significant differences in IHC testing results-derived COO classification (GCB vs. ABC) by age, gender, year of DLBCL diagnosis, geographic location of residency, type of insurance plan, tumor group stage, documentation of extranodal site or any other primary cancer history at the time of diagnosis. Discussion In this large real-world DLBCL cohort, a lower-than-expected proportion of DEL patients were identified vs. the 20-35% reported in the literature (Karube K and Campo E. Hematology 2015;52(2):97-106). This is likely due to our cohort of patients requiring clear evidence of coexpression for MYC and BCL2 (≥40% and &gt;50%, respectively) that are not related to underlying chromosomal rearrangements, and few pathologists reported levels of percent staining for IHC testing among those with documented positive results of MYC/BCL2 protein coexpression. In addition, results from this study showed that only half of cases had COO classification documented by healthcare providers, despite available IHC results. Although this study indicated lack of details in the reporting of diagnostic testing (e.g. COO identification, levels of percent staining, methods for DLBCL subgroup identification), findings should be interpreted with caution, as patients with DLBCL might have been tested but not documented in the electronic health record system or might have biomarker testing performed at sites outside of the Flatiron Health network. Disclosures Yang: F. Hoffmann-La Roche: Current Employment. Zhang:F. Hoffmann-La Roche: Current Employment. Xiao:F. Hoffmann-La Roche: Current Employment. Hammer:Roche: Consultancy, Honoraria, Research Funding; Caris Lifesciences: Honoraria; PER Med education: Honoraria; PathEdEx: Current equity holder in private company. Prime:F. Hoffmann-La Roche: Current Employment.

scholarly journals Large B-Cell Lymphoma with T-Cell–Rich Background and Nodules Lacking Follicular Dendritic Cell Meshworks: A Case Report with Complete Response to Chemotherapy and a Review of the Literature

2020 ◽  
Vol 5 (11) ◽  
pp. 561-565
Author(s):  
Walid Shalata ◽  
Ismaell Massalha ◽  
Kayed Al-Athamen
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Follicular Dendritic Cell ◽  
Large B Cell Lymphoma ◽  
Follicular Dendritic ◽  
Large B Cell

In this report, we describe a 38-year-old male with a very rare type of lymphoma, large B cell lymphoma with T cell-rich background and nodules lacking follicular dendritic cell meshworks (THRLBCL). In 2016 the patient presented hot flashes and night sweats (B-symptoms) and peripheral edema. He was treated with R-CHOP (doxorubicin, vincristine, cyclophosphamide, rituximab and Prednisone) chemotherapy, a Positron emission tomography–computed tomography (PET-CT) scan was performed after four cycles of treatment which showed radiologic complete response and blood test (complete blood count (CBC)) results showed normal ranges. As of September, 2020 he patient remains in complete remission. We searched the literature for descriptions of cases spanning the diagnostic spectrum of THRLBCL and we identified only five cases worldwide. The last reported case was in 2014 with distinctive features that were difficult to classify according to the World Health Organization criteria or previously described variants. Our patient is the sixth case of THRLBCL to be reported. He is the youngest of the reported cases and the first from Israel and the Middle East.

Cell-of-Origin in Diffuse Large B-Cell Lymphoma: Are the Assays Ready for the Clinic?

2015 ◽  
pp. e458-e466 ◽  
Author(s):  
David W. Scott
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Practical Implementation ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma worldwide and consists of a heterogeneous group of cancers classified together on the basis of shared morphology, immunophenotype, and aggressive clinical behavior. It is now recognized that this malignancy comprises at least two distinct molecular subtypes identified by gene expression profiling: the activated B-cell-like (ABC) and the germinal center B-cell-like (GCB) groups—the cell-of-origin (COO) classification. These two groups have different genetic mutation landscapes, pathobiology, and outcomes following treatment. Evidence is accumulating that novel agents have selective activity in one or the other COO group, making COO a predictive biomarker. Thus, there is now a pressing need for accurate and robust methods to assign COO, to support clinical trials, and ultimately guide treatment decisions for patients. The “gold standard” methods for COO are based on gene expression profiling (GEP) of RNA from fresh frozen tissue using microarray technology, which is an impractical solution when formalin-fixed paraffin-embedded tissue (FFPET) biopsies are the standard diagnostic material. This review outlines the history of the COO classification before examining the practical implementation of COO assays applicable to FFPET biopsies. The immunohistochemistry (IHC)-based algorithms and gene expression–based assays suitable for the highly degraded RNA from FFPET are discussed. Finally, the technical and practical challenges that still need to be addressed are outlined before robust gene expression–based assays are used in the routine management of patients with DLBCL.

scholarly journals Evolution of frontline treatment of diffuse large B-cell lymphoma: a brief review and recent update

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1933 ◽  
Author(s):  
Jung Yong Hong ◽  
Cheolwon Suh ◽  
Won Seog Kim
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Targeted Agents ◽  
Cell Of Origin ◽  
Cell Subtype ◽  
Large B Cell Lymphoma ◽  
Frontline Treatment ◽  
Double Hit ◽  
Large B Cell

Various strategies have been implemented to improve the outcomes of diffuse large B-cell lymphoma (DLBCL). In recent years, remarkable advances have been achieved, based on the discovery of cell-of-origin in DLBCL and on more effective targeted agents. This commentary will summarize recent updates on the evolution of frontline therapies for DLBCL, focusing on the upcoming promising frontline chemotherapy platforms and on activated B-cell subtype DLBCL and double-hit DLBCL.

Sign in / Sign up

Export Citation Format

Share Document