Prognostic Relevance of Immunohistochemical Subclassification of Diffuse Large B-Cell Lymphoma in Two Prospective Phase III Clinical Trials

2011 ◽  
Vol 11 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Nazik Rayman ◽  
King H. Lam ◽  
Bronno van der Holt ◽  
Clara Koss ◽  
Dennis Veldhuizen ◽  
...  
Keyword(s):  
Clinical Trials ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Prognostic Relevance ◽  
Phase Iii Clinical Trials ◽  
Large B Cell Lymphoma ◽  
Prospective Phase ◽  
Large B Cell

scholarly journals Efficacy and Safety of Lenalidomide Based Regimens in Diffuse Large B Cell Lymphoma: A Systematic Review and Meta-Analysis of Clinical Trials

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-14
Author(s):  
Wajeeha Aiman ◽  
Muhammad Ashar Ali ◽  
Rimsha Ali ◽  
Farwah N. Fatima ◽  
Nayab Mirza ◽  
...  
Keyword(s):  
Clinical Trials ◽  
B Cell ◽  
Randomized Clinical Trials ◽  
Cell Lymphoma ◽  
Meta Analysis ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Background: Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma in the US. Lenalidomide (Len), an immunomodulator, is used in the treatment of multiple hematological malignancies. This systematic review and meta-analysis aimed to assess the efficacy and safety of Lenalidomide based regimens in Newly Diagnosed (ND) and Relapsed/Refractory (R/R) DLBCL. Methods : A search was performed on PubMed, Cochrane, Embase, and Web of Science. We used the following mesh terms and Emtree terms, "Lenalidomide" OR "Revlimid" AND "diffuse large B cell lymphoma" from the inception of literature till 06/20/2020. We screened 1640 articles and included 2 randomized clinical trials (N=72) and 21 single-arm clinical trials (N=860) in this meta-analysis. We excluded case reports, case series, preclinical trials, review articles, meta-analysis, observational studies, and clinical trials not providing any information about the lenalidomide efficacy or safety in DLBCL. We used the R programming language (version 4.0.2) to conduct a meta-analysis. Results : In 23 studies (N=932), Len based regimens were used in patients with age 19-92 years (range) Table 1. In 5 trials on R/R patients (N=252), Len was used as a maintenance therapy. Cumulative overall response rate (ORR) and cumulative complete response (CR) were 0.27 (95% CI 0.21; 0.33, I2=0%) (Fig1) and 0.10 (95% CI 0.07; 0.16, 8%) (Fig2), respectively. In one phase III trial, the ORR and CR were significantly improved in the Len arm vs investigator's choice drug. In 4 trials on R/R patients (N=207), Len with monoclonal antibodies (MoAb) was used. Cumulative ORR and CR were 0.40 (95% CI 0.28; 0.54, I2=71%) and 0.28 (95% CI 0.17; 0.42, I2=72%), respectively. In a trial on R/R patients (N=33), Len with Gemcitabine, Rituximab, and Oxaliplatin was used. Cumulative ORR and CR were 0.61 (95% CI 0.43; 0.76, I2=0%) and 0.39 (95% CI 0.24; 0.57, I2=0%), respectively. In a trial on R/R patients (N=15), Len with RICE was used with ORR and CR of 0.73 (95% CI 0.47; 0.90, I2=0%) and 0.60 (95% CI 0.35; 0.81, I2=0%), respectively. In a trial on R/R patients(N=55), Len with Everolimus was used. ORR and CR were 0.27 (95% CI 0.17; 0.40, I2=0%) and 0.07 (95% CI 0.03; 0.18, I2=0%), respectively. In a trial on R/R patients (N=19), Len with R-ESHAP was used. ORR and CR were 0.79 (95% CI 0.55; 0.92, I2=0%) and 0.47 (95% CI 0.27; 0.69, I2=0%), respectively. In a phase III trial on R/R patients (N=21), Len with Gemcitabine and Rituximab was used vs. placebo The ORR and CR were significantly improved in the Len arm vs placebo. In 4 trials on ND patients (N=158), Len with R-CHOP was used and the cumulative ORR and CR were 0.94 (95% CI 0.88; 0.97, I2=12%) and 0.81 (0.75; 0.87, I2=0%), respectively. In a trial on ND patients (N=15), Len with R-EPOCH was used with ORR and CR of 0.93 (95% CI 0.65; 0.99, I2=0%) and 0.87 (95% CI 0.59; 0.97, I2=0%), respectively. In 2 trials (N=103), Len with Ibrutinib and Rituximab was used. In R/R patients (N=45), cumulative ORR and CR were 0.38 (95% CI 0.25; 0.53, I2=0%) and 0.24 (95% CI 0.14; 0.39, I2=0%), respectively. In ND patients (N=58) has ORR and CR 0.86 (95% CI 0.75; 0.93, I2=0%), respectively. In 2 trials with a combination of ND and R/R patients (N=54), Len with Rituximab and Bendamustine was used. Cumulative ORR and CR were 0.63 (95% CI 0.49; 0.75, I2=0%) and 0.39 (95% CI 0.27; 0.52, I2=0%), respectively. The most common serious treatment-related adverse events (TRAE) were infection, thromboembolism, fatigue, sepsis, respiratory, neurological, cardiac (arrhythmias), gastrointestinal, rash, seizures, and hematological side effects (Table 1). Conclusion : Based on early phase trials, Len based regimens are well tolerated and effective in the treatment of both ND and R/R DLBCL patients. Combinations of lenalidomide with Tafasitamab and R-ESHAP have shown the highest response in R/R patients and combination with R-CHOP has shown the best response in ND patients. In randomized trials, lenalidomide has shown significant improvement in the survival of DLBCL patients as compared to placebo or physician's choice drug. Additional double-blind multicenter randomized clinical trials are needed to compare the efficacy and safety of lenalidomide based regimens in DLBCL patients. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.

scholarly journals Rituximab-CHOP With Early Rituximab Intensification for Diffuse Large B-Cell Lymphoma: A Randomized Phase III Trial of the HOVON and the Nordic Lymphoma Group (HOVON-84)

2020 ◽  
Vol 38 (29) ◽  
pp. 3377-3387
Author(s):  
Pieternella Johanna Lugtenburg ◽  
Peter de Nully Brown ◽  
Bronno van der Holt ◽  
Francesco A. D’Amore ◽  
Harry R. Koene ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
Phase Iii ◽  
Free Survival ◽  
Intention To Treat ◽  
Large B Cell Lymphoma ◽  
Large B Cell

PURPOSE Immunochemotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has become standard of care for patients with diffuse large B-cell lymphoma (DLBCL). This randomized trial assessed whether rituximab intensification during the first 4 cycles of R-CHOP could improve the outcome of these patients compared with standard R-CHOP. PATIENTS AND METHODS A total of 574 patients with DLBCL age 18 to 80 years were randomly assigned to induction therapy with 6 or 8 cycles of R-CHOP-14 with (RR-CHOP-14) or without (R-CHOP-14) intensification of rituximab in the first 4 cycles. The primary end point was complete remission (CR) on induction. Analyses were performed by intention to treat. RESULTS CR was achieved in 254 (89%) of 286 patients in the R-CHOP-14 arm and 249 (86%) of 288 patients in the RR-CHOP-14 arm (hazard ratio [HR], 0.82; 95% CI, 0.50 to 1.36; P = .44). After a median follow-up of 92 months (range, 1-131 months), 3-year failure-free survival was 74% (95% CI, 68% to 78%) in the R-CHOP-14 arm versus 69% (95% CI, 63% to 74%) in the RR-CHOP-14 arm (HR, 1.26; 95% CI, 0.98 to 1.61; P = .07). Progression-free survival at 3 years was 74% (95% CI, 69% to 79%) in the R-CHOP-14 arm versus 71% (95% CI, 66% to 76%) in the RR-CHOP-14 arm (HR, 1.20; 95% CI, 0.94 to 1.55; P = .15). Overall survival at 3 years was 81% (95% CI, 76% to 85%) in the R-CHOP-14 arm versus 76% (95% CI, 70% to 80%) in the RR-CHOP-14 arm (HR, 1.27; 95% CI, 0.97 to 1.67; P = .09). Patients between ages 66 and 80 years experienced significantly more toxicity during the first 4 cycles in the RR-CHOP-14 arm, especially neutropenia and infections. CONCLUSION Early rituximab intensification during R-CHOP-14 does not improve outcome in patients with untreated DLBCL.

Prognostic Relevance of Gene Expression Using RT-PCR in Diffuse Large B-Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4559-4559
Author(s):  
Hee-Nam Kim ◽  
Je-Jung Lee ◽  
Deok-Hwan Yang ◽  
Yeo-Kyeoung Kim ◽  
Nan Young Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Rt Pcr ◽  
Pcr Assay ◽  
Gene Expressions ◽  
Prognostic Relevance ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Diffuse large B-cell lymphoma (DLBCL) is characterized by a marked degree of morphologic and clinical heterogeneity. Recently, Rosenwalt et al. (N Engl J Med 2002) reported that four gene expression “signature”, 17 genes were identified as correlated with patient outcome by DNA microarray in DLBCL. In this study, we aim to establish predictor of outcome could help to identify patients who may benefit from risk-adjusted therapies in advance. To do it, we evaluate the prognostic relevance of 17 gene expressions in 72 patients with DLBCL who received a conventional chemotherapy. Seventeen genes were studied using RT-PCR assay from paraffin-embedded sections at the time of diagnosis. The median age of the patients was 58 years (range: 21–80 years). When we initially exam an appropriative patient’s selection for survival analysis, overall survival (OS) at 2 years in patients with the international prognostic index (IPI) < 2 and IPI ≥ 2 were 95.2±4.6% and 50.6±11.8%, respectively (p = 0.009), and progression free survival (PFS) at 2 years in patients with the IPI < 2 and IPI ≥ 2 were 75.0±9.7% and 46.7±12.9%, respectively (p = 0.049). Of the 17 genes, patients with uPA expression showed a shorter OS compared with those without the gene expression. Additionally, patients with the expression of NPM3, uPA, fibronectin, or IMAGE814622 showed a shorter PFS compared with those without the gene expressions. In conclusion, these findings suggest that the gene expression profiling with simple RT-PCR assay is useful for analysis of the prognostic implications in patients with DLBCL.

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]

REPOCH compared with RCHOP for the treatment of diffuse large B-cell lymphoma of activated B-cell type.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20081-e20081
Author(s):  
Phillip Martinez-Knouse ◽  
Edward Nabrinsky ◽  
Anjana Chandran ◽  
Timothy M. Lestingi ◽  
Jacob D. Bitran
Keyword(s):  
Complete Remission ◽  
B Cell ◽  
Retrospective Analysis ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Cell Type ◽  
Large B Cell Lymphoma ◽  
Grade 3 ◽  
Large B Cell

e20081 Background: Patients with diffuse large B-cell lymphoma of activated B-cell type (DLBCL-ABC) have a worse prognosis than patients with DLBCL of germinal center origin. Recently, a phase III randomized trial of patients with DLBCL showed no improvement in response rates or progression free survival (PFS) with REPOCH compared to RCHOP. However, the PFS reported in this study was significantly better than expected, indicating that high-risk patients, such as those with DLBCL-ABC, may have been underrepresented. The optimal treatment for patients with DLBCL-ABC remains unknown. Methods: We undertook a retrospective analysis of patients with DLBCL treated in our practice from January 1, 2015 to May 31, 2019. We then examined treatment approaches and outcomes of patients treated for DLBCL-ABC. Results: We treated 136 patients with DLBCL and identified 18 of 136 patients with DLBCL-ABC. There were 9 men and 9 women with a median age of 74 years (range 26-92 years) and a median performance status of Eastern Cooperative Oncology Group 1, (0-2). The median international prognostic index score was 3. Nine of 18 patients were treated with REPOCH, 8 with RCHOP, and one with bendamustine and rituximab (BR). The stage distribution was stage I in 2 patients, stage III in 4 patients, and stage IV in 12 patients. Of 9 patients treated with REPOCH, 9 (100%) achieved a complete remission with no relapses to date. Of 8 patients treated with RCHOP, 6 (75%) achieved a complete remission and 2 had no response and died. The one patient treated with BR failed to respond and died. The median PFS for the 8 patients treated with RCHOP was 19.5 months; whereas, the PFS in the REPOCH group had not been reached at a median follow up of 2 years. Grade 3 and 4 toxicities were more common in the RCHOP group and included cardiomyopathy in 1 patient and two episodes of neutropenic fever (one resulting in septic shock and death). There were no grade 3 or 4 toxicities in the REPOCH group. Conclusions: In this retrospective analysis, our patients with DLBCL-ABC treated with REPOCH had better overall outcomes. A prospective trial in this subset of DLBCL patients is warranted.

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