The Efficacy and Safety of the Addition of Rituximab to CHOP or a CHOP-Like Regimen In First Line Therapy for Diffuse Large B-Cell Lymphoma (DLBCL): A Meta-Analysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4913-4913
Author(s):  
Aaron T Gerds ◽  
Laura C Michaelis ◽  
Danielle Shafer
Keyword(s):  
Disease Control ◽  
Clinical Oncology ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Forest Plot ◽  
Newly Diagnosed ◽  
Free Survival ◽  
American Society

Abstract Abstract 4913 Background: The addition of rituximab to cytotoxic chemotherapy has become standard in the initial treatment of DLBCL. However, estimations of the overall effect of the addition of rituximab to chemotherapy vary widely in the published literature. To date, no meta-analyses of rituximab in DLBCL have been published. We performed a comprehensive systematic review to compare chemotherapy with rituximab-chemotherapy in studies of newly-diagnosed DLBCL. The primary endpoint was OS; additional endpoints included disease control (DC), complete response (CR), and regimen-related toxicity (RRT). Disease control was assessed in each study as the time to treatment failure, event-free survival, progression free survival or time to progression. Methods: A comprehensive search for randomized trials (RCTs) comparing the addition of rituximab to chemotherapy was conducted in MEDLINE (January 1997 through April 2010). Also, meeting proceedings from American Society of Clinical Oncology, American Society of Hematology, European Society of Clinical Oncology and European Hematology Association, and studies listed on www.clinicaltrials.gov were manually searched for any supplementary abstracts, presentations or updates that were not identified in the original database search. The analysis included only RCTs comparing rituximab-chemotherapy with chemotherapy alone in patients with newly diagnosed DLBCL. Chemotherapy regimens were limited to CHOP or CHOP-like regimens. All three authors independently assessed each study's quality and performed blinded data extraction with conflict resolution by majority consensus. Given the inclusion of studies with both young and elderly patients, as well as HIV seropositive patients, we pooled data using a random effects model, with the estimate of heterogeneity being taken from the inverse variance fixed effect model. Results: Overall, seven RCTs involving 3539 patients with newly diagnosed DLBCL met inclusion criteria and were included in the meta-analysis. All studies were published as full-text articles. None of the studies were blinded. Studies from North America, Central America, and Europe were incorporated. The funnel plot for OS and Egger's test (1.37; 95% CI -2.25 to 4.99) did not indicate a significant publication bias. The test of heterogeneity among all RCTs was statistically significant in all endpoints. The pooled odds ratio (OR) demonstrated an increased OS for patients treated with rituximab-chemotherapy compared to chemotherapy alone (OR 0.71; 95% CI: 0.57 to 0.89). Similar improvements in CR (OR 1.64; 95% CI: 1.23, 2.17) and DC (OR 0.56; 95% CI: 0.46, 0.70) were observed in the patients treated with the rituximab containing regimens. Due to variable RRT reporting across studies, a formal meta-analysis of toxicity was not completed. In addition, varied data reporting precluded formal analysis of any differences in benefit between the International Prognostic Index groups. Conclusions: Our meta-analysis of data from more than 3500 patients with newly diagnosed DLBCL demonstrates that the addition of rituximab to chemotherapy improves the odds of OS and DC by 29% and 44%, respectively, as compared to chemotherapy alone. The survival benefit was independent of age (data not shown). This comprehensive systematic analysis enumerates and confirms the benefit of rituximab-based therapy in previously untreated DLBCL. Forest Plot for OS. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Sentinel Lymph Node Biopsy for Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Joint Clinical Practice Guideline

2012 ◽  
Vol 30 (23) ◽  
pp. 2912-2918 ◽  
Author(s):  
Sandra L. Wong ◽  
Charles M. Balch ◽  
Patricia Hurley ◽  
Sanjiv S. Agarwala ◽  
Timothy J. Akhurst ◽  
...  
Keyword(s):  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Disease Control ◽  
Clinical Oncology ◽  
Surgical Oncology ◽  
Breslow Thickness ◽  
Newly Diagnosed ◽  
Evidence Review ◽  
Regional Disease ◽  
American Society

Purpose The American Society of Clinical Oncology (ASCO) and Society of Surgical Oncology (SSO) sought to provide an evidence-based guideline on the use of lymphatic mapping and sentinel lymph node (SLN) biopsy in staging patients with newly diagnosed melanoma. Methods A comprehensive systematic review of the literature published from January 1990 through August 2011 was completed using MEDLINE and EMBASE. Abstracts from ASCO and SSO annual meetings were included in the evidence review. An Expert Panel was convened to review the evidence and develop guideline recommendations. Results Seventy-three studies met full eligibility criteria. The evidence review demonstrated that SLN biopsy is an acceptable method for lymph node staging of most patients with newly diagnosed melanoma. Recommendations SLN biopsy is recommended for patients with intermediate-thickness melanomas (Breslow thickness, 1 to 4 mm) of any anatomic site; use of SLN biopsy in this population provides accurate staging. Although there are few studies focusing on patients with thick melanomas (T4; Breslow thickness, > 4 mm), SLN biopsy may be recommended for staging purposes and to facilitate regional disease control. There is insufficient evidence to support routine SLN biopsy for patients with thin melanomas (T1; Breslow thickness, < 1 mm), although it may be considered in selected patients with high-risk features when staging benefits outweigh risks of the procedure. Completion lymph node dissection (CLND) is recommended for all patients with a positive SLN biopsy and achieves good regional disease control. Whether CLND after a positive SLN biopsy improves survival is the subject of the ongoing Multicenter Selective Lymphadenectomy Trial II. Copyright © 2012 American Society of Clinical Oncology and Society of Surgical Oncology. All rights reserved. No part of this document may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission by the American Society of Clinical Oncology and Society of Surgical Oncology.

Quantitative Defects Of Cellular Immune Responses In Patients With Newly-Diagnosed Diffuse Large B-Cell Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4733-4733
Author(s):  
Pairaya Rujirojindakul
Keyword(s):  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Conditional Logistic Regression ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
Color Flow ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Altered immune status in non-Hodgkin lymphoma is characterized by undesired autoimmune phenomena and frequent occurrence of infections. The immune defects may be responsible for the initiation, maintenance and progression of malignant clone. We therefore evaluated immune effector cells between 35 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) and 34 age- and sex- matched healthy controls using three-color flow cytometry. For patients with DLBCL, there were 19 males and 16 females with a mean age of 59.9 ± 15.6 years. There were 6, 17 and 13 patients with ECOG > 2, stage III-IV and high intermediate to high International Prognostic Index, respectively. We found significant decreases in CD3+CD4+, CD4/CD8 ratio, CD4 central memory (CD4+CD45RO++CD27+) and B cells (Figure 1). From conditional logistic regression, only CD4/CD8 ratio showed significant association with being cases with the odds ratio of 0.29 (95% CI 0.12, 0.68). Disclosures: No relevant conflicts of interest to declare.

scholarly journals Event-Free Survival at 12 Months (EFS12) from Diagnosis Is a Robust Endpoint for Disease-Related Survival in Patients with Follicular Lymphoma in the Immunochemotherapy Era

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1664-1664 ◽  
Author(s):  
Matthew J Maurer ◽  
Herve Ghesquieres ◽  
Stephen M Ansell ◽  
Carrie A Thompson ◽  
Grzegorz S. Nowakowski ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Conflicts Of Interest ◽  
B Cell Lymphoma ◽  
French Population ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Current Standard ◽  
Free Survival ◽  
Related Mortality

Abstract Background: Follicular lymphoma (FL) is an indolent lymphoma generally considered incurable with current standard therapies. Recent advances have resulted in prolongation of overall survival (OS) for patients with FL such that death from competing causes may now limit the mortality impact of FL in some patient groups. Identification of patients for whom FL related mortality is expected to be minimal, or conversely those at high risk of disease related mortality, is highly clinically relevant. We recently reported (Maurer et al, JCO 2014;32:1066-73) that event-free survival (EFS) at 24 months from diagnosis is a robust endpoint for disease related outcome in patients with diffuse large B cell lymphoma (DLBCL). Here we use the same approach to assess if landmark timepoints of EFS can stratify subsequent OS in FL. Methods: All newly diagnosed grade 1-3a FL patients enrolled on the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER) from 2002-2011 were eligible. Patients with grade 3b FL, transformation, or presence of DLBCL at diagnosis were excluded. EFS was defined as time from diagnosis to progression, relapse, re-treatment, or death due to any cause. EFS12 was defined based on EFS status 12 months after date of diagnosis; we also assessed EFS at 24 months. OS was defined as time from a specific timepoint (diagnosis, event, or EFS12) until death due to any cause. OS was compared to age and sex matched survival in the general US population using an expected survival approach and standardized mortality ratios (SMR) and 95% confidence intervals (CI). Outcomes were examined in all patients as well as selected subsets defined by initial treatment. Replication was performed using a Lyon, France hospital registry of newly diagnosed grade 1-3a FL patients enrolled from 2002-2010 with survival compared to French population data. Results: 936 patients with grade 1-3a FL were eligible from the MER. The median age at diagnosis was 60 years (range 19-91) and 53% were male. 86% had grade 1-2 disease and 14% grade 3a disease. 23% had high-risk disease (FLIPI score ≥3). 347 (37%) were initially treated with alkylator or anthracyline based immunochemotherapy (IC), 113 (12%) rituximab monotherapy (RM), and 318 (34%) were initially observed; the remaining patients received radiation for limited stage disease (8%), chemotherapy without rituximab (4%), or other therapy (5%). At a median follow-up of 59 months (range 1-131), 403 patients (43%) had an event and 120 patients (13%) had died; 155 patients (17%) failed to achieve EFS12. From diagnosis, patients with FL had inferior OS compared to the general population (SMR=1.24, 95% CI: 1.03-1.48, p=0.018); results were similar for patients with grade 1-2 (SMR=1.23) and grade 3a (SMR=1.29) disease. The survival deficit was eliminated in patients who achieved EFS12 (SMR=0.85, 95% CI: 0.66-1.09, p=0.20, Fig 1a), and so we did not pursue modeling EFS24. In contrast, patients with a non-death event (relapse, retreatment, or progression) within 12 months of diagnosis had inferior subsequent OS (SMR=3.90, 95% CI: 2.89-5.25, p=4.8x10-19, Fig 1b). These results were replicated in 153 FL patients from the Lyon registry: patients who achieved EFS12 had equivalent subsequent OS to the general French population (SMR=0.82, 95% CI: 0.39-1.72, p=0.60, Fig 1c), while patients who failed to achieve EFS12 had poor subsequent OS (SMR=4.16, 95% CI: 1.34-12.91, p=0.013, Fig 1d). In subset analysis of the MER, patients achieving EFS12 initially treated with IC (SMR=0.98, 95% CI: 0.63-1.54, p=0.93), RM (SMR=0.66, 95% CI: 0.31-1.38, p=0.27), or observation (SMR=0.73, 95% CI: 0.47-1.15, p=0.18) had equivalent OS to the population. In contrast, for patients not achieving EFS12, OS after event was inferior for those treated with IC (SMR=15.0, 95% CI: 10.22-22.05, p=2.0x10-43) or RM (SMR=4.96, 95% CI: 1.24-19.84, p=0.023), while trending towards inferior for those initially observed (SMR=1.55, 95% CI: 0.81-2.99, p=0.19). Summary: Events within the first 12 months of diagnosis are associated with poor OS in FL, especially in patients treated with IC, while patients achieving EFS12 have excellent subsequent survival, overall and in the main treatment subsets. Prognosis for FL patients should be recalibrated at 12 months from diagnosis. EFS12 will be useful in counseling and should be considered as an endpoint in studies of newly diagnosed FL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Primary Mediastinal B Cell Lymphoma Treated with CHOP-Like Chemotherapy with or without Rituximab: 5-Year Results of the Mabthera International Trial Group (MInT) Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1612-1612 ◽  
Author(s):  
Mathias Witzens-Harig ◽  
Anthony D Ho ◽  
Evelyn Kuhnt ◽  
Marek Trneny ◽  
Michael Rieger ◽  
...  
Keyword(s):  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Bulky Disease ◽  
Long Term Outcome ◽  
Free Survival ◽  
The Impact

Abstract Abstract 1612 Purpose The aim of this subgroup analysis of the MInT study was to evaluate the impact of chemotherapy and rituximab in primary mediastinal B cell lymphoma (PMBCL) in comparison to other diffuse large B-cell lymphoma (DLBCL). Extended follow-up was needed to establish long-term effects. Patients and Methods Eligible for the randomized open-label MInT study were patients aged 18–60 years with DLBCL who had 0–1 risk factors according to age-adjusted International Prognostic Index (aaIPI), stage II-IV disease, or stage I disease with bulk. Patients were randomly assigned to six cycles of CHOP-like regimens with or without rituximab. Consolidating radiotherapy was given to sites of primary bulky disease. Results Of 824 patients enrolled, 87 had PMBCL and 627 other types of DLBCL. Rituximab increased the rates of complete remission (unconfirmed) in both PMBCL (from 54% to 80%; p =.015) and DLBCL (from 72% to 87%; p<.001). In PMBCL rituximab virtually eliminated progressive disease (PD) (2.5% vs 24%; p =.006), whereas without rituximab PD was more frequent in PMBCL than in DLBCL (24% vs 10%; p =.023). With a median observation time of 62 months for PMBCL and 73 months for DLBCL, the 5-year event-free survival was improved by rituximab for PMBCL (79.1% vs 47.3%; p =.011) and for DLBCL (76.9% vs 59.7%; p <.001). Furthermore, 5-year progression-free survival was improved by rituximab for PMBCL (89.8% vs 60.1%; p=.006) and DLBCL (81.1% vs. 67.8%; p <.001). Overall survival benefit was similar for DLBCL (92.0% vs 80.9%; p <.001) and PMBCL (90.2% vs 78.3%; p =.234). Conclusion Addition of rituximab to 6 cycles of CHOP-like chemotherapy improved long-term outcome for young patients with PMBCL and aaIPI 0–1 and eliminated differences in outcome between PMBCL and DLBCL. Disclosures: No relevant conflicts of interest to declare.

Assessment of Value Using the American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) Frameworks for Novel Therapies for the Hematologic Malignancies

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3578-3578
Author(s):  
Matthew C Cheung ◽  
Sierra Cheng ◽  
Erica McDonald ◽  
Vanessa Arciero ◽  
Mahin Qureshi ◽  
...  
Keyword(s):  
Correlation Coefficient ◽  
Clinical Oncology ◽  
European Society ◽  
Medical Oncology ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Hematologic Malignancies ◽  
Novel Therapies ◽  
Free Survival ◽  
American Society

Abstract Introduction The cost of cancer care is rising to unsustainable levels, predominantly driven by an increase in expenditures for novel therapies. In the era of biologic therapies, these excessive costs are disproportionately borne by patients with hematologic malignancies. Although the American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) have both developed frameworks to determine the relative value associated with new solid tumor therapies (and specifically with ESMO, to the exclusion of therapies in hematology), it is unclear if they can be applied in the assessment of value of treatments for blood cancers. Methods We evaluated the value of new therapies for hematologic malignancies using the ASCO (version 1 from August 10, 2015 and version 2 from May 31, 2016) and ESMO (version 1 or v1) frameworks. All US Food and Drug Administration, European Medicinal Agency, or Health Canada approved parenteral therapies for hematologic malignancies from 2006-2015 were identified. A systematic review of randomized controlled trials (RCTs) for these therapies was conducted. Two reviewers independently scored the trials using the ASCO value framework v1 (range of scores -20 to 130), v2 (lower range undefined to 180) and ESMO Magnitude of Clinical Benefit Scale (range 1-5). Disagreements were descriptively presented and resolved by consensus. The concurrent validity between the ASCO and ESMO scores was measured by the Spearman correlation coefficient. Results Twenty-three RCTs in malignant hematology were identified and scored. Seven of 23 studies reported primary outcomes unique to hematologic malignancies (for example, time-to-progression in myeloma, cytogenetic response in chronic myeloid leukemia, and symptomatic response in multicentric Castleman's), other than the main outcomes used to derive ASCO/ESMO scores (overall and progression-free survival). The median ASCO v1 score for the trials was 24 (IQR 22-40, min 6 and max 53). The median ASCO v2 score was 26.7 (IQR 17.4-37.6, min -33.3 and max 116.3). The median ESMO score was 2 (IQR 2-3, min 1 and max 4). Using the ASCO v1 framework, 10 studies resulted in disagreements in scoring, predominantly due to variable interpretations of the scoring system. Two studies could not be scored. One study did not report toxicity grades and another study of maintenance rituximab in lymphoma did not report on conventional oncology outcomes that could fit into the ASCO model. Using the ASCO v2 framework, 14 studies resulted in disagreements, predominantly due to differences in scoring toxicities. With the ESMO Scale, 12 studies resulted in disagreements, most occurring due to variable interpretations in scoring survival or progression-free survival outcomes when median values were not provided in the study publication. Two studies could not be scored with the ESMO Scale. One study did not report hazard ratios and another study's reported outcomes did not fit the ESMO scoring options. The correlation coefficient between ASCO v1 and ESMO scores was 0.10 (95% CI: -0.37 to 0.53), suggesting that the correlation was not significantly different from chance only. The coefficient between ASCO v2 and ESMO was -0.21 (95% CI: -0.59 to 0.24) and between ASCO v1 and ASCO v2 was 0.30 (95% CI: -0.15 to 0.65). Conclusions Current value frameworks are challenging to apply to therapies for hematologic malignancies. When studies could be scored, the correlations between ASCO (v1 and v2) and ESMO results were poor, suggesting that these frameworks may not reliably identify the value of therapies in hematology. Consideration for the unique outcomes and toxicities in this population is warranted. The ASCO and ESMO frameworks continue to evolve, and a partnership with societies representing hematologists and their patients would be fruitful. Disclosures No relevant conflicts of interest to declare.

scholarly journals Prognostic implication of human papillomavirus types in cervical cancer patients: a systematic review and meta-analysis

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Yuanyuan Xu ◽  
Yichao Qiu ◽  
Shuang Yuan ◽  
Hongjing Wang
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Hpv 16 ◽  
Free Survival ◽  
American Society ◽  
Hpv 18

Abstract Background To estimate the prognostic relevance of human papillomavirus (HPV) 16 and HPV 18 in patients with cervical cancer. Method We searched PubMed, EMBASE, American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO), CNKI, and Wanfang databases to search primary articles illustrating the survival outcomes in cervical cancer patients with or without HPV 16/18 infection. A meta-analysis was conducted to generate a combined hazard ratio (HR) with 95% confidence intervals (CI) for progression-free survival (PFS), disease free survival (DFS) and overall survival (OS). Results A total of 13 studies were included. Our meta-analysis revealed that HPV 16 positive did not have any impact on OS (HR, 0.76; 95% CI = 0.37–1.54; P = 0.44). Cervical cancer patiensts infected with HPV 18 had worse OS (HR, 1.66; 95% CI = 1.28–2.17; P = 0.0001), DFS (HR, 2.10; 95% CI = 1.73–2.54; P < 0.0001) and worse PFS (HR, 2.97; 95% CI = 1.69–5.23; P = 0.00012) compared with those not infected with HPV 18. cervical cancer patiensts infected with HPV 18 had worse PFS compared with those infected with HPV 16 ((HR, 1.34; 95% CI = 1.06–1.70; P = 0.01). Conclusion Cervical cancer patients infected with HPV 18 had worse survival compared with cervical cancer patients with HPV 16 infection.

scholarly journals Diagnosis-to-Treatment Interval Is an Important Clinical Factor in Newly Diagnosed Diffuse Large B-Cell Lymphoma and Has Implication for Bias in Clinical Trials

2018 ◽  
Vol 36 (16) ◽  
pp. 1603-1610 ◽  
Author(s):  
Matthew J. Maurer ◽  
Hervé Ghesquières ◽  
Brian K. Link ◽  
Jean-Philippe Jais ◽  
Thomas M. Habermann ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Odds Ratio ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
Clinical Factors ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Purpose Selection bias in clinical trials has consequences for scientific validity and applicability of study results to the general population. There is concern that patients with clinically aggressive disease may not have enrolled in recent diffuse large B-cell lymphoma (DLBCL) trials due to the consent process and the inability to delay therapy for eligibility evaluation. We have examined the diagnosis-to-treatment interval (DTI) and its association with clinical factors and outcome in a clinic-based observational cohort of patients with DLBCL from the United States. Validation of results was performed in an independent, clinical trial-based cohort from Europe. Patients and Methods Patients were prospectively enrolled in the University of Iowa and Mayo Clinic Specialized Programs of Research Excellence Molecular Epidemiology Resource (MER; N = 986) or the Lymphoma Study Association (LYSA) LNH-2003 clinical trials program (N = 1,444). All patients received anthracycline-based immunochemotherapy at initial diagnosis. Associations of DTI with clinical factors and outcome were examined. Outcome was assessed using event-free survival at 24 months from diagnosis (EFS24). Results Median (range) DTI was 15 days (0 to 155 days in the MER and 23 days (0 to 215 days) in LYSA. Shorter DTI was strongly associated with adverse clinical factors, including elevated lactate dehydrogenase levels, poor performance status, B symptoms, and higher International Prognostic Index in both cohorts (all P < .001). Longer DTI was associated with improved EFS24 in both the MER (per-week odds ratio, 0.80; 95% CI, 0.74 to .0.87) and LYSA (per-week odds ratio, 0.90; 95% CI, 0.86 to 0.94); association with EFS24 remained significant after adjustment for International Prognostic Index. Conclusion DTI is strongly associated with prognostic clinical factors and outcome in newly diagnosed DLBCL. DTI should be reported in all clinical trials of newly diagnosed DLBCL and future trials should take steps to avoid selection bias due to treatment delay.

scholarly journals A phase 2 trial of standard-dose cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and rituximab plus bevacizumab for patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: SWOG 0515

Blood ◽  
2012 ◽  
Vol 120 (6) ◽  
pp. 1210-1217 ◽  
Author(s):  
Alison T. Stopeck ◽  
Joseph M. Unger ◽  
Lisa M. Rimsza ◽  
Michael LeBlanc ◽  
Brent Farnsworth ◽  
...  
Keyword(s):  
B Cell ◽  
Standard Dose ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Left Ventricular ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Phase 2 Trial ◽  
Large B Cell

Abstract S0515 was a phase 2 trial to determine whether the addition of bevacizumab to cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) plus rituximab (R-CHOP) would improve progression-free survival (PFS) without adding significant toxicity in patients with newly diagnosed advanced diffuse large B-cell lymphoma. A total of 73 patients were enrolled. For the 64 eligible patients, median age was 68 years, and 60% had International Prognostic Index scores more than or equal to 3. The observed 1- and 2-year PFS estimates were 77% and 69%, respectively. These PFS estimates were not statistically different from the expected PFS for this population if treated with R-CHOP alone. Grade 3 or higher toxicities were observed in 81% of patients, including 2 grade 5 events. The majority of serious toxicities were hematologic but also included 5 patients with gastrointestinal perforations, 4 patients with thrombotic events, and 11 patients who developed grade 2 or 3 left ventricular dysfunction. Higher baseline urine VEGF and plasma VCAM levels correlated with worse PFS and overall survival. In conclusion, the addition of bevacizumab to R-CHOP chemotherapy was not promising in terms of PFS and resulted in increased serious toxicities, especially cardiac and gastrointestinal perforations. This study is registered at www.clinicaltrials.gov as #NCT00121199.

Cell of origin, germinal center versus nongerminal center, determined by immunohistochemistry on tissue microarray, does not correlate with outcome in patients with relapsed and refractory DLBCL

Blood ◽  
2005 ◽  
Vol 106 (10) ◽  
pp. 3383-3385 ◽  
Author(s):  
Craig H. Moskowitz ◽  
Andrew D. Zelenetz ◽  
Tarun Kewalramani ◽  
Paul Hamlin ◽  
Simone Lessac-Chenen ◽  
...  
Keyword(s):  
De Novo ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Second Line ◽  
Cell Of Origin ◽  
Free Survival ◽  
Significant Difference ◽  
The Common

AbstractA number of prognostic factors affect outcome in patients with relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL), including refractory disease and the second-line age-adjusted international prognostic index. In de novo DLBCL, the cell of orgin, as determined by expression microarray analysis or immunohistochemistry (IHC), predicts event-free survival (EFS). We evaluated the cell of origin, as well as other pathologic markers of outcome, on the repeat biopsy specimen of 88 transplantation-eligible patients undergoing ifosfamide, carboplatin, etoposide (ICE) second-line chemotherapy (SLT) followed by high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) to see if were they prognostic in the salvage setting. Pretreatment clinical factors were well balanced between the cohorts. There was no significant difference in response to SLT, HDT, event-free or overall survival based on the cell of origin or any of the common pathologic markers examined. The cell of origin as determined by IHC does not predict outcome in transplantation-eligible patients with relapsed or primary refractory DLBCL.

Poly(ADP-ribose) polymerase inhibitors as maintenance treatment in patients with newly diagnosed advanced ovarian cancer: a meta-analysis

2020 ◽  
Vol 16 (10) ◽  
pp. 585-596 ◽  
Author(s):  
Ezzeldin M Ibrahim ◽  
Ahmed A Refae ◽  
Ali M Bayer ◽  
Emad R Sagr
Keyword(s):  
Ovarian Cancer ◽  
Randomized Clinical Trials ◽  
Brca Mutation ◽  
Meta Analysis ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Polymerase Inhibitors

Aim: Poly(ADP-ribose) polymerase inhibitors (PARPIs) improved progression-free survival among patients with recurrent ovarian cancer. This meta-analysis examined the effectiveness of PARPIs as maintenance strategy for newly diagnosed patients with advanced high-grade ovarian cancer with or without mutations. Materials & methods: Using defined selection criteria, a literature search identified four eligible randomized clinical trials involving 2386 patients. Results: Compared with placebo maintenance, PARPIs achieved a 46% reduction in the risk of progression or death as compared with placebo (hazard ratio: 0.54; 95% CI: 0.39–0.73; p < 0.0001). That benefit was shown in all clinical subgroups: among those with BRCA mutation, with negative/unknown BRCA mutation, and in those with homologous recombination deficient tumors. Data about the effect on overall survival are still premature. Conclusion: In patients with newly diagnosed advanced ovarian cancer, PARPIs maintenance after standard therapy achieved a significant improvement in progression-free survival as compared with placebo, overall and in all subgroups.

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