High risk patients with diffuse large B cell lymphoma are not enrolled on clinical trials.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19058-e19058
Author(s):  
Alfadel Alshaibani ◽  
Christina Lee ◽  
Sarah Camp Rutherford ◽  
Kah Poh Loh ◽  
Andrea M Baran ◽  
...  
Keyword(s):  
Clinical Trials ◽  
B Cell ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Large B Cell Lymphoma ◽  
Large B Cell

e19058 Background: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. In this study, we explore reasons for non-enrollment in clinical trials for DLBCL and implications on trial design and interpretation. Methods: This is a retrospective analysis of patients (pts) with a pathological diagnosis of DLBCL or high grade B-cell lymphoma (HGBL) at University of Rochester (4/14-6/16) and New York-Presbyterian Hospital/Weill Cornell Medicine (NYP/WCM) (4/14-4/17).Ten clinical trials were opened during this time. Participants were divided into 3 groups: those treated in trial, those not enrolled in trial because of need for urgent treatment, and those not enrolled in trial for any other reason. We used a center-stratified Cox proportional hazards model to estimate association of trial enrollment with progression-free survival (PFS; time from start of treatment until progression/death or the last date the pt was known to be progression free) and overall survival (OS). Results: We identified 263 pts; 17% (n = 45) enrolled in a trial. Reasons for non-enrollment included not meeting eligibility criteria (n = 98), physician choice (n = 50), and pt choice (n = 38). For 32 pts, reasons were unclear. Of the 50 pts who were not enrolled because of physician choice, the primary reason for non-enrollment was the need for urgent treatment (n = 46). Pts who needed urgent treatment had higher risk clinical features compared with pts in trial (Table). Compared with those treated in trial and those not enrolled in trial for any other reason, those not enrolled in trial due to need for urgent treatment had an inferior PFS (HR 2.61, 95% CI 1.23–5.16) and OS (HR 2.27, 95% CI 1.21–4.06). Conclusions: At 2 academic institutions, 52% of patients with DLBCL or HGBL required urgent chemotherapy and failed to enroll on trials. Exclusion of such patients limits the applicability and generalizability of clinical trials in DLBCL. This barrier must be overcome so clinical trials may better reflect true DLBCL demographics. [Table: see text]

scholarly journals Osteopontin expression and its relationship with prognostic factors in diffuse large B-cell lymphoma

2019 ◽  
Vol 11 (3) ◽  
Author(s):  
Gilberto Barranco ◽  
Edith Fernández ◽  
Silvia Rivas ◽  
Roxana Quezada ◽  
Dolores Nava ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cox Proportional Hazards ◽  
Biological Behavior ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

The aim of this study is to explore the expression of osteopontin (OPN) and its relationship with prognostic factors and survival in diffuse large B cell lymphoma (DLBCL). A tissue microarray was performed for immunohistochemical evaluation. Contingency tables were analyzed for trends; chi-square test was used to determine differences between groups. Univariate and multivariate Cox proportional hazards-regression analyses were performed to evaluate the impact of prognostic factors on survival. Expression of OPN was observed in 28%. It was different in non-germinal center DLBCL (P=0.04). The mean overall survival (OS) was lower in patients with positive OPN expression (19.762; CI 95% 14.269-25.255) it was not significant (P=0.123). It is not possible to establish a clear relationship between the expression by immunohistochemistry of osteopontin and a poor prognosis but it would be important to complement the analysis with other techniques as PCR or NGS that allow us to assess the influence of the isoforms and post-translational modifications of OPN on the biological behavior of DLBCL. Our findings indicate that OPN expression could be associated with a more aggressive variant of lymphoma: non-germinal center DLBCL.

Accrual Of Patients With Relapsed and Refractory DLBCL Onto Clinical Trials

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3041-3041
Author(s):  
Ashley Marton ◽  
Abbas Kezouh ◽  
Sarit Assouline
Keyword(s):  
Clinical Trials ◽  
B Cell ◽  
Standard Therapy ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Tumor Board ◽  
Rapid Progression ◽  
Cell Transplant ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background New drug development in diffuse large B cell lymphoma (DLBCL) has become a very active area of research in the last several years with the advent of monoclonal antibodies and targeted therapies. We sought to determine the rate of accrual of patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) onto early phase clinical trials, and hurdles to their enrolment by performing a retrospective analysis of all DLBCL cases diagnosed at our institution from 01/2006 to 03/2012. This time span represents an active time period for clinical trials in lymphoma at our institution. Methods DLBCL cases were identified through the hospital tumor registry. Patients were included in the analysis if they had any diagnosis ofDLBCL relapsed or refractory to standard therapy. Baseline demographics and disease characteristics, details of treatment, responses, relapse, evaluation for clinical trials and participation in clinical trials were determined by review of hospital charts. Only Phase I and II clinical trials were considered for this analysis. Results Of a total of 284 patients, 76 had relapsed/refractory disease, 10 of 25 had a successful autologous stem cell transplant (ASCT), and there is insufficient data on 1 patient. Of the remaining 65, 11 (17%) made it to trial. The median age was 65, 34 were male, median number of prior therapies was 2, 74% had at least one comorbidity and 46% had at least 2. Sixty-two percent of patients had de novo DLBCL, 18% transformed and 20% had a composite lymphoma including DLBCL. Reasons for failing to enroll on trial included prohibitive comorbidity (21%), rapid progression (15%), decision for palliation (15%), prior second malignancy (9%), thrombocytopenia (13%), CNS disease (9%), proximity to ASCT (2%), no protocol available(6%), palliative radiation (6%). Patients on trial tended to be younger (58.4 vs. 65.8 years), and to have a lower IPI (mean 3.1 vs 3.4). There was no difference in the number of prior of therapies (2.31 vs. 2.26) or number of comorbidities (2.18 vs 2.21). However, out of the 11 who made it to trial, 7 patients had failed ASCT (46.7% of patients who failed ASCT) vs. 4 (10%) who never had a transplant (p=0.005, Fisher’s exact test). Among the relapsed and refractory cases, 81% of cases were discussed at tumor board. Conclusions Although our study is small, we demonstrate that in an active research center, where a large number of R/R DLBCL patients are discussed at tumor board during which information about clinical trials is disseminated, a minority of patients with DLBCL not responding to standard therapy make it to trial.Patients having failed an ASCT are more successfully enrolled onto clinical trials. Interestingly, a similar accrual rate was seen in relapsed non-small cell lung cancer (Baggstrom,J Thor Oncol 2011) and similar barriers to enrolment were found for solid tumor patients (Lara, JCO 2001). Accrual of R/R DLBCL patients onto clinical trials is possible but challenging. A multi-institution analysis is underway. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Understanding Immune Evasion and Therapeutic Targeting Associated with PD-1/PD-L1 Pathway in Diffuse Large B-cell Lymphoma

2019 ◽  
Vol 20 (6) ◽  
pp. 1326 ◽  
Author(s):  
Moo-Kon Song ◽  
Byeong-Bae Park ◽  
Jieun Uhm
Keyword(s):  
Clinical Trials ◽  
B Cell ◽  
Immune Evasion ◽  
Immune Checkpoint ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Targeting Therapy ◽  
Large B Cell Lymphoma ◽  
Programmed Death ◽  
Large B Cell

In tumor microenvironment, the programmed death 1 (PD-1) immune checkpoint has a crucial role of mechanism of T cell exhaustion leading to tumor evasion. Ligands of PD-1, programmed death ligand 1/2 (PD-L1/L2) are over-expressed in tumor cells and participate in prolonged tumor progression and survivals. Recently, clinical trials for patients who failed to obtain an optimal response prior to standardized chemotherapy in several solid cancers have been focused on targeting therapy against PD-1 to reduce disease progression rates and prolonged survivals. Since various inhibitors targeting the immune checkpoint in PD-1/PD-L1 pathway in solid cancers have been introduced, promising approach using anti-PD-1 antibodies were attempted in several types of hematologic malignances. In diffuse large B cell lymphoma (DLBCL) as the most common and aggressive B cell type of non-Hodgkin’s lymphoma, anti-PD-1 and anti-PD-L1 antibodies were studies in various clinical trials. In this review, we summarized the results of several studies associated with PD-1/PD-L1 pathway as an immune evasion mechanism and described clinical trials about targeting therapy against PD-1/PD-L1 pathway in DLBCL.

Barriers to enrollment of patients with recurrent diffuse large B-cell lymphoma onto clinical trials

2015 ◽  
Vol 56 (9) ◽  
pp. 2747-2749 ◽  
Author(s):  
Ashley Marton ◽  
Abbas Kezouh ◽  
Tina Petrogiannis-Haliotis ◽  
Sarit Assouline
Keyword(s):  
Clinical Trials ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Barriers To Enrollment ◽  
Large B Cell

scholarly journals Clinical impact of molecular features in diffuse large B-cell lymphoma and follicular lymphoma

Blood ◽  
2016 ◽  
Vol 127 (2) ◽  
pp. 181-186 ◽  
Author(s):  
Julia R. Pon ◽  
Marco A. Marra
Keyword(s):  
Clinical Trials ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Cancer Biology ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Molecular Features ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Our understanding of the pathogenesis and heterogeneity of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) has been dramatically enhanced by recent attempts to profile molecular features of these lymphomas. In this article, we discuss ways in which testing for molecular features may impact DLBCL and FL management if clinical trials are designed to incorporate such tests. Specifically, we discuss how distinguishing lymphomas on the basis of cell-of-origin subtypes or the presence of other molecular features is prognostically and therapeutically significant. Conversely, we discuss how the molecular similarities of DLBCL and FL have provided insight into the potential of both DLBCL and FL cases to respond to agents targeting alterations they have in common. Through these examples, we demonstrate how the translation of our understanding of cancer biology into improvements in patient outcomes depends on analyzing the molecular correlates of treatment outcomes in clinical trials and in routinely treated patients.

scholarly journals Prognostic Efficacy of the RTN1 Gene in Patients with Diffuse Large B-Cell Lymphoma

2021 ◽  
Author(s):  
Mohamad Zamani-Ahmadmahmudi ◽  
Seyed Mahdi Nassiri ◽  
Amir Asadabadi
Keyword(s):  
Gene Expression ◽  
Clinical Outcome ◽  
Gene Expression Data ◽  
Proportional Hazards ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cox Proportional Hazards ◽  
Expression Data ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Gene expression profiling has been vastly used to extract the genes that can predict the clinical outcome in patients with diverse cancers, including diffuse large B-cell lymphoma (DLBCL). With the aid of bioinformatics and computational analysis on gene expression data, various prognostic gene signatures for DLBCL have been recently developed. The major drawback of the previous signatures is their inability to correctly predict survival in external data sets. In other words, they are not reproducible in other datasets. Hence, in this study, we sought to determine the gene(s) that can reproducibly and robustly predict survival in patients with DLBCL. Gene expression data were extracted from 7 datasets containing 1636 patients (GSE10846 [n=420], GSE31312 [n=470], GSE11318 [n=203], GSE32918 [n=172], GSE4475 [n=123], GSE69051 [n=157], and GSE34171 [n=91]). Genes significantly associated with overall survival were detected using the univariate Cox proportional hazards analysis with a P value <0.001 and a false discovery rate (FDR) <5%. Thereafter, significant genes common between all the datasets were extracted. Additionally, chromosomal aberrations in the corresponding region of the final common gene(s) were evaluated as copy number alterations using the single nucleotide polymorphism (SNP) data of 570 patients with DLBCL (GSE58718 [n=242], GSE57277 [n=148], and GSE34171 [n=180]). Our results indicated that reticulon family gene 1 (RTN1) was the only gene that met our rigorous pipeline criteria and associated with a favorable clinical outcome in all the datasets (P<0.001, FDR<5%). In the multivariate Cox proportional hazards analysis, this gene remained independent of the routine international prognostic index components (i.e., age, stage, lactate dehydrogenase level, Eastern Cooperative Oncology Group [ECOG] performance status, and number of extranodal sites) (P<0.0001). Furthermore, no significant chromosomal aberration was found in the RTN1 genomic region (14q23.1: Start 59,595,976/ End 59,870,966).

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