Meta Analysis of Grade 3 and/or 4 Toxicities in Low-Grade Non-Hodgkin Lymphoma (LG-NHL) Patients Receiving Maintenance Rituximab (MR) Therapy: Impact of Schedule on Toxicity

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2704-2704
Author(s):  
Chadi Nabhan ◽  
Dana Villines ◽  
Tina V. Valdez ◽  
Michele Ghielmini ◽  
Shu-Fang Hsu Schmitz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Research Funding ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Comparative Trial ◽  
Progression Free Survival ◽  
Low Grade ◽  
Front Line ◽  
Grade 3 ◽  
The Impact

Abstract Abstract 2704 Background: MR has improved the outcome and progression-free survival (PFS) in patients with follicular lymphoma (FL) in front-line and relapsed settings. However, maintenance schedules have been empirically designed based on either B-cell depletion kinetics or rituximab levels, with no consensus on the optimal regimen. Overall, toxicities have been predictable and tolerable but the impact of MR schedule on toxicities has not been previously reported and could influence selection of maintenance regimens. Methods: Using PubMed, prospective clinical trials employing MR were identified. Data presented in abstract form or at meetings were deemed incomplete and thus excluded. Data were analyzed from published manuscripts as percentages of subjects experiencing an adverse event (AE). Percentages were considered as the unit of analysis as this adjusted for the uneven sample sizes. Data were collected for overall Grade 3 and/or Grade 4 toxicity (AE reported at any phase of treatment) and was further categorized as AE occurring during initial treatment or during MR. Grade 1 and 2 toxicities were excluded from meta-analysis, given lack of consistent reporting. No grade 5 toxicities were reported. The incidence, severity, and type of toxicity was analyzed by type of induction (Rituximab (R) vs. R plus chemotherapy), histology (FL vs. FL plus other LG-NHL), setting (front-line vs. relapsed), and MR schedule (one dose every 2 months vs. one dose every 3 months vs. 4 doses every 6 months). Results: Nine clinical trials involving 1,928 patients were included in this Meta analysis (4 of which were randomized controlled in the MR phase). Of those, 1,004 patients received MR. The mean percentage of Grade 3/4 toxicities during any phase of treatment was 26% (95% CI = 0.12–51.88) but when restricted to the MR phase; it was 12.88% (95% CI = 6.50–19.26). Toxicities were numerically higher in patients receiving R induction plus chemotherapy versus R induction alone and in patients receiving MR for relapsed disease versus newly diagnosed patients, but did not reach statistical significance (P = 0.661 and 0.517, respectively). However, patients receiving MR every 2 months were significantly more likely to develop grade 3 and 4 toxicities compared to patients receiving MR every 6 months (P = 0.005). No statistical differences were demonstrated between the 2 vs. 3 months schedules or when comparing the 3 vs. 6 months schedules (P = 0.342 and 0.267, respectively) (Table 1). Statistically significant differences were also found in studies restricted to FL versus others allowing non-FL histologies (P = 0.025) with the FL patients experiencing more toxicity than others. The most frequently reported toxicities were neutropenia and infections. There were no treatment-related deaths in any of the arms. Conclusions: Approximately 13% of patients receiving MR experience grade 3 and/or 4 toxicities, mainly consisting of neutropenia and infections. MR given every 6 months appears to provide the least grade 3 and 4 toxicities. There is a suggestion of increased toxicity in FL histologies. It is important to note that this meta-analysis did not address efficacy and only a true comparative trial can definitively establish the relative risk/benefit ratios amongst MR schedules. Disclosures: Nabhan: Genentech: Research Funding, Speakers Bureau. Ghielmini:Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau. Smith:Genentech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Meta Analysis of Grade 3 and/or 4 Toxicities in Follicular (FL) and Mantle Cell (MCL) Non-Hodgkin Lymphoma (NHL) Patients Receiving Maintenance Rituximab (MR): Impact of Schedule, Histology, and Induction Regimen

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3654-3654
Author(s):  
Chadi Nabhan ◽  
Dana Villines ◽  
Brian C-H Chiu ◽  
Nicholas J. Ollberding ◽  
Tina V. Valdez ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Research Funding ◽  
Meta Analysis ◽  
Random Effect ◽  
Cochrane Library ◽  
Induction Phase ◽  
Low Grade ◽  
Front Line ◽  
Grade 3 ◽  
The Impact

Abstract Abstract 3654 Background: MR has improved the outcome and progression-free survival (PFS) of patients (pts) with FL and MCL. However, maintenance schedules have been empirically designed with no consensus on the optimal regimen. While toxicities are usually predictable, the impact of MR schedule on toxicities has not been previously reported and could influence selection of maintenance regimens. We analyzed grade 3 and/or 4 adverse events (AE) in FL and MCL pts enrolled in prospective MR trials in order to compare AEs by MR schedule, histology, and setting (front-line and relapsed). Methods: A systematic search of the Medline (Pub-Med, Google Scholar, Cochrane Library) electronic database was performed to identify prospective clinical trials employing MR in FL and MCL. The following search terms were used: “MR, maintenance immunotherapy, maintenance therapy, low-grade lymphoma, NHL, MCL, and FL”. Abstracts and studies using MR after autologous stem cell transplantation or radioimmunotherapy were excluded. The number of AE reported was considered as the unit of analysis. Data for overall Grade 3 and/or Grade 4 toxicity (AE reported at any phase of treatment) were further categorized as an AE occurring during the induction phase or the maintenance phase. The incidence, severity, and type of toxicity were analyzed by type of induction (R vs. R+chemotherapy), histology (FL, MCL and FL plus other low-grade histologies), setting (front-line vs. relapsed), and MR schedule (one dose every 2 months vs. one dose every 3 months vs. 4 weekly doses every 6 months; all given for 2 years) and analysis was performed using t-tests or one-way ANOVA weighted means by either the total sample or the MR phase sample. Means were calculated using both fixed-effect and random-effect models Results: Thirteen clinical trials met criteria, including six trials which were randomized controlled in the MR phase. Of the total 3,100 pts, 1,263 received MR. The mean percentage of Grade 3/4 toxicities during any phase of treatment was 26% (95% CI = 0.12–51.88) but in the MR phase, it was only 12.88% (95% CI = 6.50–19.26). The overall mean number of grade 3/4 toxicities during any phase of treatment was 173.85 (95% CI = 167.76–179.95) and it was 60.5 (95% CI 58–63) in the MR phase. Toxicities were significantly different between induction therapy regimens, front-line and the relapsed settings and histologies (all P < 0.001). Pts receiving MR every 2 months encountered more grade 3 and 4 toxicities (mean percentage = 33%, mean = 97.46, 95% CI = 94.15–100.77) compared to 3 months (mean percentage = 21%, mean = 29.24, 95% CI = 27.92 –30.57) and 6 months (mean percentage = 13%, mean = 11.62, 95% CI = 10.70–12.54) schedules (P < 0.001). Pts receiving R+ chemo induction had more AEs compared to those receiving R induction [(mean=73.9 (95% CI 70.8–77.0) vs. 7.5 (95% CI 6.4–8.5), P<0.001]. Pts receiving MR in front-line had more AEs compared to those receiving MR in relapsed disease [mean= 73.1 (95% CI 69.9–76.6) vs. 43.3 (95% CI 41.3–45.3), P<0.001]. Pts with FL had more AEs compared to those with MCL [mean=72.9 (95% CI 69.8–75.9) vs. 15.3 (95% CI 13.2–17.3), P<0.001] Neutropenia and infections were the most common reported individual toxicities. Conclusions: Approximately 13% of patients receiving MR experience grade 3 and/or 4 toxicities, mainly neutropenia and infections. MR given every 6 months appears to cause fewer toxicities. Importantly, this meta-analysis did not compare relative efficacy amongst the three most commonly used MR schedules, but may be helpful in advising patients of relative risks amongst the three schedules. Disclosures: Nabhan: Genentech: Research Funding, Speakers Bureau. Ghielmini:Roche: Honoraria, Research Funding. Smith:Genentech/Roche: Data Safety Monitoring Board and advisory Board attendance Other.

Meta-analysis of outcomes of VEGF and EGFR targeted biologic therapy in relapsed metastatic colorectal cancer (mCRC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 534-534 ◽  
Author(s):  
David Chan ◽  
Eva Segelov ◽  
Jeremy David Shapiro ◽  
Timothy Jay Price ◽  
Christos Stelios Karapetis ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Kinase Inhibitors ◽  
Biologic Therapy ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Biologic Agents ◽  
First Line ◽  
Grade 3 ◽  
Line Setting ◽  
The Impact

534 Background: Biologic therapies used in treatment of mCRC are expensive and there is debate about their value. We examined the impact of biologic therapy on overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3/4 toxicity for patients beyond first-line treatment. Methods: MEDLINE, EMBASE, and Cochrane libraries were searched for randomized studies in relapsed mCRC comparing treatment containing targeted therapy to the same treatment without targeted therapy. Biologic agents were classed as: EGFR-inhibitors (EGFR-I), VEGF antibody/trap and VEGFR tyrosine kinase inhibitors (TKI). Only KRAS wild-type patients were included for EGFR-I analysis. Results were aggregated according to standard meta-analytic techniques. Results: 10 studies evaluating 5,847 patients were identified. Considering subgroups and lines, OS and PFS benefit was demonstrated in all groups across all lines except for OS in 2nd line EGFR-I use (which may be due to subsequent crossover). A benefit to ORR was seen with EGFR-I 2nd line (Pooled ORR benefit +24%, Odds Ratio (OR) 4.44, 95% CI 3.20-6.18), EGFR-I 3rd line and beyond (Pooled ORR benefit +16%), VEGF antibody/trap (Pooled ORR benefit +7.2%, OR 2.00, 95% CI 1.57-2.54) and VEGFR TKI (Pooled ORR benefit +1.9%, OR 2.05, 95% CI 1.27-3.30). The risk of grade 3/4 toxicity was greater with the addition of all targeted agents. Conclusions: The use of VEGF and EGFR targeted biologic agents beyond first-line setting in mCRC results in a benefit to OS, PFS and ORR for all agents except for OS benefit with second-line EGFR-I. This benefit comes at the cost of increased toxicity. [Table: see text]

Clinical and prognostic features of adult patients with gangliogliomas.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2063-2063
Author(s):  
Shlomit Yust-Katz ◽  
Mark Daniel Anderson ◽  
Diane Liu ◽  
Ying Yuan ◽  
Greg Fuller ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Histological Grade ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Tumor Grade ◽  
Histologic Grade ◽  
Low Grade ◽  
Prognostic Features ◽  
Grade 3 ◽  
The Impact

2063 Background: Gangliogliomas (GG) represent less than 1% of primary brain tumors in adults. Little is known regarding prognostic features, clinical characteristics or the impact of treatment on patient (pt) outcomes. Methods: In this IRB approved retrospective study, our neuro-oncology longitudinal database was screened for pts with GG from 1992-2012. 67 adult pts (age>18) were identified. Results: 60 pts presented with low grade GG and 7 with anaplastic GG. The median age at diagnosis was 27 years (18-59). 22 pts developed recurrent disease (18 low grade and 4 high grade) with a median time to recurrence of 87 weeks from surgery. 7 of the pts with low grade GG had malignant transformation to a malignant tumor (anaplastic GG or GBM). 22 pts received radiation therapy, 16 at diagnosis. 14 pts received chemotherapy at recurrence. Pts with incomplete resections or higher grade tumors were more likely to receive chemotherapy or radiation. The median overall survival (OS) time for these pts was not reached with a median follow-up time of 4.6 years. The 2-, 5- and 10-year OS were 98%, 87%, and 76%. Factors on univariate analysis that were significantly associated with OS were KPS at presentation (HR 10.1; 95% CI 2.6, 39.1; p = 0.0008), extent of resection (EOR) (biopsy vs gross total; HR 12.1; 95% CI 2.3, 63.6; p = 0.003), histologic grade (Grade 1-2 vs Grade 3-4; HR 0.06; 95% CI 0.01, 0.3; p = 0.0002), and seizure control following surgery (Engel I vs Engel 2-3; HR 0.1; 95% CI 0.01, 0.9; p = 0.02). Factors on univariate analysis that were significantly associated with progression free survival (PFS) were EOR (biopsy vs gross total; HR 4.0; 95% CI 1.4, 11.9; p = 0.01) and histologic grade (Grade 1-2 vs .Grade 3-4; HR 0.3; 95% CI 0.08, 0.8; p = 0.02). On multivariate analysis, EOR is most significant for PFS (p = 0.01), while tumor grade is most significant for OS (p = 0.004). Conclusions: While GG have an excellent prognosis, malignant histological grade, diagnosis with a biopsy only, poor initial KPS, and presence of seizures following surgery could indicate a worse prognosis. The role of chemotherapy and radiation therapy for incompletely resected or inaccessible low grade GG is unclear.

Addition of Cyclophosphamide, on Demand, to Lenalidomide and Corticosteroids in Patients with Relapsed/Refractory Multiple Myeloma, a Retrospective Review of a Single Centre Experience

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1842-1842
Author(s):  
Majed Alahmadi ◽  
Esther Masih-Khan ◽  
Eshetu G Atenafu ◽  
Limore Arones ◽  
Christine Chen ◽  
...  
Keyword(s):  
At Risk ◽  
Confidence Interval ◽  
Research Funding ◽  
Progression Free Survival ◽  
Free Survival ◽  
Lower Upper ◽  
Start Date ◽  
On Demand ◽  
Grade 3 ◽  
The Impact

Abstract Introduction The lenalidomide + dexamethasone combination (Len-dex) is an established regimen for myeloma patients (pts) with relapsed or refractory disease. In order to prolong the benefit of this effective regimen, the Myeloma Program at Princess Margaret Cancer Centre has routinely added a third agent, oral weekly cyclophosphamide (Cy), to Len-dex at the time of progression. We have now retrospectively analyzed the results of this pt cohort to assess the response rate (RR), duration of response (DOR), progression-free survival (PFS), overall survival (OS) and toxicity of the Len-dex-Cy regimen subsequent to progression on Len-dex. Methods The Princess Margaret Myeloma Database identified 54 patients that received Len-dex-Cy for a minimum of 4 weeks following Len-dex as a doublet between 12/2007-12/2014. Hematologic responses were assessed using modified IMWG consensus criteria. Survival times were measured in months both from the start of Len-dex and the time of addition of Cy up to date of event of interest or end of follow-up. The impact of diagnostic and clinical variables on PFS and OS were also assessed in both cases using the log rank test. Results Baseline pt characteristics at addition of Cy included: median age 66 yrs; Hgb 107 g/L; creatinine 76 umol/L; albumin 36g/L; ANC 2.5 109/L; and median platelet count 158 109/L . Myeloma isotypes were IgG (61%), IgA (19%), and FLC (20%). The median number of prior regimens including Len-dex was 2; 80% pts had undergone prior ASCT. The dose of added Cy ranged between 250-500mg once weekly. Twenty-six percent patients experienced dose reductions primarily due to cytopenias. Overall, Len-dex-Cy was well tolerated with grade 3-4 toxicities in < 20% (Table 1). The mean duration of Len-Dex-Cy therapy was 8.9 months (range 0.9 - 37.7). The overall RR (≥ PR) was 41%; however clinical benefit was seen in 85% (≥ SD) pts. The median PFS was 8 months (95 % CI 5.8- 10.3 months) from addition of Cy and 25 months (95 % CI 17.3- 32.5 months) from start of Len-dex. The median OS was 24.5 months (95 % CI 15.2-41.8 months) from addition of Cy and 50.1 months (95 % CI 40.6-70.4 months) from start of Len-dex (Figure 1). Significant adverse factors for PFS were del(13q) from start of Len-dex and presence of anemia at the time of addition of Cy (p=0.027) and (p=0. 031) respectively. Decreased baseline serum albumin at the time of addition of Cy was identified as a significant factor for shorter OS (p=0.004). Conclusions 1) The addition of Cy in pts with myeloma progressing on Len-dex resulted in a clinically meaningful extension of disease control with an acceptable safety profile; 2) The effectiveness of adding a third agent to pts with progression on a doublet regimen raises the possibility that only a limited number of resistant myeloma clone(s) is/are responsible for the progression; 3) Although subject to many limitations, the results of this sequential "on demand" approach compare favorably with our previously reported phase 2 study of the Len+ prednisone+ Cy ("CPR") regimen in which triple-drug therapy was given throughout (PFS: 25 vs 16.1 months; OS: 50.1 vs 27.6 months) (Reece et al, Br J Haematol 2015; 168: 46-54); 4) future prospective studies evaluating a strategy of adding a third agent to a doublet ( such as Len-dex) "on demand" versus using triple therapy throughout the relapse would be worthwhile; a number of potential agents, including Cy as well as other newer anti-myeloma drugs, might be candidates for such studies. Table 1. Grade 3-4 toxicities associated with Len-Dex-Cy therapy in Len-dex relapsed patients Toxicity No. of patients (%) Grade 3-4 Thrombocytopenia 4 (7.7) Grade 3-4 Anemia 10 (18.8) Grade 3-4 Hematuria 1 (1.9) Febrile Neutropenia 2 (3.9) Infections 7 (12.9) Secondary Malignancy 2 (3.7) Table 2. Years PFS Rate 95% Confidence Interval Status Lower Upper Events so far Number at risk 1 0.8675 0.74204 0.93454 7 45 2 0.5591 0.41457 0.68112 23 29 3 0.3433 0.21795 0.47228 34 15 Table 3. Years OS Rate 95% Confidence Interval Status Lower Upper Events so far Number at risk 1 0.9426 0.83250 0.98114 3 48 2 0.7428 0.59831 0.84183 13 37 5 0.4136 0.25436 0.56596 25 11 Figure 1. Progression Free Survival (PFS) from the start date of Len-Dex Figure 1. Progression Free Survival (PFS) from the start date of Len-Dex Figure 2. OS of patients from start date of Len-Dex with 95% CI Figure 2. OS of patients from start date of Len-Dex with 95% CI Disclosures Chen: Celgene: Consultancy, Honoraria, Research Funding. Kukreti:Celgene: Honoraria; Roche: Honoraria; Janssen Ortho: Honoraria; Amgen: Honoraria; Lundbeck: Honoraria. Tiedemann:Amgen: Honoraria; Janssen Ortho: Honoraria; Celgene: Honoraria. Prica:Celgene: Honoraria; Janssen: Honoraria. Reece:Amgen: Honoraria; Bristol-Myers Squibb: Research Funding; Lundbeck: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Onyx: Consultancy; Otsuka: Research Funding; Millennium Takeda: Research Funding; Otsuka: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Onyx: Consultancy; Merck: Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Honoraria; Lundbeck: Honoraria; Novartis: Honoraria, Research Funding; Millennium Takeda: Research Funding.

scholarly journals Effectiveness and Safety of S-1-Based Therapy Compared with 5-Fluorouracil-Based Therapy for Advanced Colorectal Cancer: A Meta-Analysis

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Jiaxiang Ye ◽  
Jiawei Chen ◽  
Lianying Ge ◽  
Aiqun Liu ◽  
Shaozhang Zhou
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Attractive Alternative ◽  
Significant Difference ◽  
Different Populations ◽  
Grade 3

Objectives.The aim of our study was to compare the efficacy and safety of S-1-based therapy (SBT) versus 5-fluorouracil-based therapy (FBT) for advanced colorectal cancer (ACRC).Methods.A meta-analysis of all eligible randomized controlled trials (RCTs) was performed using RevMan 5.1.0 software.Results.A total of 1625 patients from twelve RCTs including 820 patients in the SBT group and 805 patients in the FBT group were available for analysis. The meta-analysis of overall survival (hazards ratio HR = 0.94, 95% CI = 0.80–1.10), progression-free survival (HR = 1.03, 95% CI = 0.91–1.18), and overall response rate (odds ratio OR = 1.23, 95% CI = 1.00–1.53) showed no statistical significance between SBT group and FBT group. The statistically significant differences in the meta-analysis indicated less incidence of graded 3-4 neutropenia (OR = 0.49, 95% CI = 0.35–0.68) and nausea/vomit (OR = 0.41, 95% CI = 0.23–0.72) in the SBT group, and there was no statistically significant difference in the incidence of grade 3-4 anemia, thrombocytopenia, leucopenia, diarrhea, and treatment-related deaths between two groups.Conclusions.SBT had similar efficacy and better safety than FBT and was an attractive alternative to FBT for patients of ACRC, but further investigations in different populations would be needed to confirm it.

The Improved Efficacy of Bortezomib Containing Induction Regimens (BCIR) Versus Non-Bortezomib Containing Induction Regimens (NBCIR) in Transplant-Eligible Patients with Multiple Myeloma (MM): Meta-Analysis of Phase III Randomized Controlled Trials (RCTs),

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3994-3994
Author(s):  
Ajay K. Nooka ◽  
Jonathan L. Kaufman ◽  
Madhusmita Behera ◽  
Charise Gleason ◽  
Amelia Langston ◽  
...  
Keyword(s):  
Research Funding ◽  
Mixed Model ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Response Rates ◽  
Phase Iii ◽  
P Value ◽  
Cell Transplant ◽  
Odds Ratios ◽  
Grade 3

Abstract Abstract 3994 Introduction: Patients with MM undergoing autologous stem cell transplant (ASCT) achieving complete response (CR) or very good partial response (VGPR) have prolonged progression free survival (PFS) and overall survival (OS) compared to the patients that achieve <VGPR prior to ASCT (Lahuerta JJ et al., 2008; Moreau P et al., 2011). Therefore it is of profound significance to attain the best response with induction therapies to obtain the better long-term outcomes. The response rates have significantly improved since the introduction of bortezomib, a proteasome inhibitor, in the induction therapies for myeloma. We performed a meta-analysis to evaluate the efficacy of the addition of bortezomib to the existing regimens used in induction therapy. Methods: We searched Medline, Embase, Cochrane databases and ASH, ASCO conference proceedings from 01/2000 through 08/2011 for publications and abstracts to identify the phase III RCTs comparing BCIR vs. NBCIR in transplant-eligible patients with myeloma. A meta-analysis was performed using both the fixed (Mantel-Haenszel) and random (DerSimonain and Laird) models to calculate the risk difference with the comparator arm to evaluate the rates of CR, ≥VGPR, ORR, PFS, OS and toxicities. Altogether, we identified 4 RCTs (two published articles and unpublished data from two RCTs including 2086 patients). The consistency of results (effect sizes) among studies was investigated by means of two heterogeneity tests, the χ 2-based Cochran's Q test, and the I2 Statistic. We considered that heterogeneity was present when the P value of the Cochran's Q test was <.1 and I 2 statistic was > 50%. Results: Q-statistic for ORR (P =0.338; df =3; I2 = 11.1); ≥VGPR (P =0.175; df =3; I2 = 39.53); CR (P =0.677; df =3; I2 = 0) suggests homogeneity across studies. Pooled odds ratios of overall response rates (ORR), ≥VGPR, CR with BCIR vs. NBCIR were 2.619 (P <0.000; 95% CI: 2.103–3.261); 3.558 (P <0.000; 95% CI: 2.908–4.354); 2.739 (P <0.000; 95% CI: 2.072–3.621) respectively indicating BCIR result in improved efficacy. Similar results were translated post-ASCT demonstrating the superiority of BCIR over NBCIR. Post-ASCT ORR (p =0.141; df =3; I2 = 45.03); ≥VGPR (P =0.442; df =3; I2 = 0); CR (P =1.00; df =3; I2 = 0) suggest homogeneity. Pooled odds ratios of ORR, ≥VGPR, CR post-ASCT for BCIR vs. NBCIR were 1.907 (P <0.000; 95% CI: 1.431–2.639); 2.43 (P <0.000; 95% CI: 2.025–2.914); 2.406 (P <0.000; 95% CI: 1.966–2.945) respectively. The pooled hazard ratios (HR) for 3 year PFS and OS were HR 0.723 (95% CI 0.620–0.844; P =0.000); 3 year OS HR 0.789 (95% CI 0.651–0.957; P =0.016) respectively in favor of BCIR. The relative risk (RR) of selected ≥grade 3 toxicities was higher with BCIR. RR of peripheral neuropathy (PN) was 2.469 (95% CI 1.848–3.297; P =0.000) and infection with herpes-zoster virus (HZV) was 2.197 (95% CI 1.368–3.529; P =0.001). The RR of a thromboembolic event (TEE) with BCIR was 0.8 (95% CI 0.56–1.15; P =0.206). Conclusion: Our mixed model meta-analysis demonstrates that the addition of bortezomib to the induction regimens in the transplant-eligible patients with MM results in improved ORR, ≥VGPR, CR, PFS and OS compared with the NBCIR. Known bortezomib related grade 3 toxicities are higher with BCIR recommending appropriate PN monitoring and HZV prophylaxis. The pooled estimates of response and survival strongly favor inclusion of bortezomib in the induction regimens. Disclosures: Kaufman: Millenium, Onyx, Novartis, Keryx: Consultancy; Merck, Celgene: Research Funding. Gleason:Celgene, Merck, Millenium: Consultancy. Flowers:Genentech/Roche (unpaid): Consultancy; Celgene: Consultancy; Millennium/Takeda: Research Funding; Wyeth: Research Funding; Novartis: Research Funding. Lonial:Millennium: Consultancy; Novartis: Consultancy; Celgene: Consultancy; BMS: Consultancy; Onyx: Consultancy; Merck: Consultancy.

The impact of interval cytoreduction and age in advanced-stage ovarian cancer: A GOG ancillary study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5056-5056
Author(s):  
Stuart M. Lichtman ◽  
James Java ◽  
John L. Lovecchio ◽  
Dennis Chi ◽  
William P. Tew ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cox Regression ◽  
Residual Disease ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Ancillary Study ◽  
Primary Surgery ◽  
The Impact

5056 Background: To determine if an age group exists for which interval cytoreductive surgery (ICS) in patients with suboptimal residual disease at primary surgery influences progression free survival (PFS) and overall survival (OS) among women with advanced ovarian cancer treated on GOG 182. Methods: GOG 182 was a prospective, randomized trial of first-line chemotherapy in patients with advanced ovarian cancer. Patients with both optimal and suboptimal residual disease were included, and those with suboptimal residual were considered for ICS, with intent registered and stratified prior to randomization. Patients were randomized to one of five chemotherapy arms, employing combinations of either two or three agents delivered intravenously, with a control arm of paclitaxel and carboplatin. A retrospective analysis was approved by the GOG Ancillary Study Committee to investigate the influence of age on treatment and outcomes. In that analysis, Cox regression was used to identify independent prognostic factors and estimate their covariate effects on the adjusted PFS and OS of patients with suboptimal residual disease. Statistical significance was set at p<0.05. Results: Among the entire eligible study population, 28% (n=1,042) were registered with suboptimal residual disease (> 1 cm) and 109 of these patients elected to undergo ICS. Hazard ratios (HR) were determined for patients undergoing ICS with reference to patients with suboptimal disease not undergoing ICS. Based on the most current follow-up data, the HR for progression or death was not statistically different between the groups, but the HR of death alone was significant at 0.72 (95% CI: 0.57–0.92, p=0.008). There was no significant association of age with ICS in either the PFS or the OS model. Conclusions: In this trial, a patient’s age did not influence the effect of ICS on PFS or OS. There is no demonstrable benefit in PFS associated with ICS, but there was a statistically significant improvement in OS. To elucidate this finding, further study is warranted, likely in the form of a meta-analysis incorporating data from other prospective trials.

scholarly journals A Comparison Between Chemo-Radiotherapy Combined With Immunotherapy and Chemo-Radiotherapy Alone for the Treatment of Newly Diagnosed Glioblastoma: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Montserrat Lara-Velazquez ◽  
Jack M. Shireman ◽  
Eric J. Lehrer ◽  
Kelsey M. Bowman ◽  
Henry Ruiz-Garcia ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Combined Therapy ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Care Group ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Grade 3

BackgroundImmunotherapy for GBM is an emerging field which is increasingly being investigated in combination with standard of care treatment options with variable reported success rates.ObjectiveTo perform a systematic review of the available data to evaluate the safety and efficacy of combining immunotherapy with standard of care chemo-radiotherapy following surgical resection for the treatment of newly diagnosed GBM.MethodsA literature search was performed for published clinical trials evaluating immunotherapy for GBM from January 1, 2000, to October 1, 2020, in PubMed and Cochrane using PICOS/PRISMA/MOOSE guidelines. Only clinical trials with two arms (combined therapy vs. control therapy) were included. Outcomes were then pooled using weighted random effects model for meta-analysis and compared using the Wald-type test. Primary outcomes included 1-year overall survival (OS) and progression-free survival (PFS), secondary outcomes included severe adverse events (SAE) grade 3 or higher.ResultsNine randomized phase II and/or III clinical trials were included in the analysis, totaling 1,239 patients. The meta-analysis revealed no statistically significant differences in group’s 1-year OS [80.6% (95% CI: 68.6%–90.2%) vs. 72.6% (95% CI: 65.7%–78.9%), p = 0.15] or in 1-year PFS [37% (95% CI: 26.4%–48.2%) vs. 30.4% (95% CI: 25.4%–35.6%) p = 0.17] when the immunotherapy in combination with the standard of care group (combined therapy) was compared to the standard of care group alone (control). Severe adverse events grade 3 to 5 were more common in the immunotherapy and standard of care group than in the standard of care group (47.3%, 95% CI: 20.8–74.6%, vs 43.8%, 95% CI: 8.7–83.1, p = 0.81), but this effect also failed to reach statistical significance.ConclusionOur results suggests that immunotherapy can be safely combined with standard of care chemo-radiotherapy without significant increase in grade 3 to 5 SAE; however, there is no statistically significant increase in overall survival or progression free survival with the combination therapy.

scholarly journals Long-Term Outcome of Patients with Low-Grade Follicular Lymphoma Treated with Yttrium-90 Ibritumomab Tiuxetan: The Mayo Clinic Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2809-2809 ◽  
Author(s):  
Muhamad Alhaj Moustafa ◽  
Ricardo Parrondo ◽  
Gregory Wiseman ◽  
Jennifer Peterson ◽  
Thomas E. Witzig ◽  
...  
Keyword(s):  
Median Time ◽  
Research Funding ◽  
Progression Free Survival ◽  
Low Grade ◽  
Ibritumomab Tiuxetan ◽  
Entire Cohort ◽  
Grade 3 ◽  
Yttrium 90

Background Follicular lymphoma (FL) is the second most common lymphoma accounting for approximately 15% of all non-Hodgkin's lymphoma (NHL). Yttrium-90 ibritumomab tiuxetan [(90)Y-IT; Zevalin] is a radio-immunoconjugate (RIC) which targets CD20. It is approved in relapsed/refractory low-grade NHL and as consolidation after upfront induction chemoimmunotherapy for FL. This study analyzed patients with previously untreated (UFL) or relapsed/refractory low-grade FL (RFL) treated at our institution with (90)Y-IT. It represents the largest reported cohort for therapeutic use of (90)Y-IT in low-grade FL. Methods Medical records of patients with low-grade FL (WHO grade 1-2) who received treatment with (90)Y-IT at Mayo Clinic Cancer Center between January 2003 and December 2018 were analyzed. Overall response rate (ORR) and complete response rate (CR) were calculated. Progression-free survival (PFS), time to next therapy (TTNT), and overall survival (OS) were analyzed using the Kaplan-Meier method. Results Our cohort consists of 137 patients - 29% (40/137) with UFL and 71% (97/137) with RFL. The median age at diagnosis was 60 years (range, 18-86) with 54% (74/137) males. The median number of previous treatments in RFL patients was 1 (range, 1-5). ECOG performance status at the time of treatment was 0 in 90% and 1 in 10% of patients. 87% (119/137) had stage III/IV disease at the time of (90)Y-IT therapy. The median follow up from the time of (90)Y-IT therapy was 10.2 years (95% CI; 8.8, 11.6); 69% (95/137) of patients are alive. The ORR was 100% in UFL with 93% (37/40) CR while ORR in UFL was 93% (90/97) with 73% (71/97) CR. 45% (48/108) of the CR patients remain in continuous CR (CCR) with a median follow-up of 7 years (95% CI; 5.2, 9.9). CCR was observed in 55% (22/40) of UFL patients compared to 27% (26/97) of RFL patients. 63% (86/137) of patients had relapsed. More relapses occurred in the RFL group (69/97; 71%) compared to the UFL group (17/40; 43%), (p=0.002). In the entire cohort, the median PFS was 2.5 years (95% CI; 2.1, 3.5) and TTNT was 3.6 years (95% CI; 2.5, 4.7). Median PFS was significantly higher in UFL group compared to RFL group- 4.1 years (95% CI; 2.3, NR) vs 2.2 years (95% CI; 1.6, 3.1), respectively (Figure 1-A). Median TTNT was higher in UFL group compared to RFL group- NR (95% CI; 4.1 years, NR) vs 2.4 years (95% CI; 2, 3.6), respectively (Figure 1-B). Median OS (entire cohort) was 18 years (95% CI; 15.8, NR) with no statistically significant difference between UFL group and RFL group; NR (95% CI; NR, NR) vs 18 years (95% CI; 12.3, 20.5), respectively (Figure 1-C). Transformation to high grade lymphoma was seen in 19% (18/97) in RFL group compared to 2.5% (1/40) in UFL group, (p=0.005). Median time to transformation was 4.3 years (range, 1-11). More patients developed therapy-related myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) in the RFL group 14% (14/97) compared to 2.5% (1/40) in the UFL group (p= 0.02). Median time to develop MDS/AML was 3.3 years (range, 0-9.7). Grade ³3 neutropenia was observed in 46% of patients with median time to recovery of 21 days (range, 2-706). Grade ³3 thrombocytopenia was observed in 47% of patients with median time to recovery of 23 days (range, 7-548). Eighteen patients required growth factors support and 14 required transfusions. Non-hematologic AEs included mild to severe fatigue in 35 patients. Conclusion Radio-immunoconjugate therapy with (90)Y-IT is an effective single-agent regimen for low-grade FL. The response and survival data in this large real-world cohort is superior to the pivotal trials of this agent conducted nearly 20 years ago. The data in untreated FL is also of interest and provides the rationale for our current randomized phase 2 trial in untreated FL (https://clinicaltrials.gov/show/NCT02320292). Long-term complete remission (>7 years) was seen in 35% of the study population. Based on these promising results, clinical trials combining RIC with novel agents that could potentiate its effects are warranted. Figure 1 (A) Progression-free survival; comparing time to progression or death after (90)Y-IT treatment between previously untreated patients (UFL) and patients with relapsed/refractory FL (RFL), (B) Time to next therapy; comparing time to starting next line of treatment after (90)Y-IT treatment between UFL and RFL, (C) Overall survival; comparing time to death from all causes after (90)Y-IT treatment between UFL and RFL. Figure 1 Disclosures Tun: DTRM Biopharma: Research Funding; TG Therapeutics: Research Funding; BMS: Research Funding; Curis: Research Funding; Celgene: Research Funding; Mundi-pharma: Research Funding. OffLabel Disclosure: Yttrium-90 ibritumomab tiuxetan [(90)Y-IT; Zevalin] is a radio-immunoconjugate (RIC) which targets CD20. It is approved in relapsed/refractory low-grade NHL and as consolidation after upfront induction chemoimmunotherapy for FL. We are discussing its use as a frontline therapy in low grade FL.

scholarly journals Uncertainty in the impact of liver support systems in acute-on-chronic liver failure: a systematic review and network meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Klementina Ocskay ◽  
Anna Kanjo ◽  
Noémi Gede ◽  
Zsolt Szakács ◽  
Gabriella Pár ◽  
...  
Keyword(s):  
Liver Failure ◽  
Support Systems ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Bioartificial Liver ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Liver Support ◽  
Bioartificial Liver Support ◽  
The Impact

Abstract Background The role of artificial and bioartificial liver support systems in acute-on-chronic liver failure (ACLF) is still controversial. We aimed to perform the first network meta-analysis comparing and ranking different liver support systems and standard medical therapy (SMT) in patients with ACLF. Methods The study protocol was registered with PROSPERO (CRD42020155850). A systematic search was conducted in five databases. We conducted a Bayesian network meta-analysis of randomized controlled trials assessing the effect of artificial or bioartificial liver support systems on survival in patients with ACLF. Ranking was performed by calculating the surface under cumulative ranking (SUCRA) curve values. The RoB2 tool and a modified GRADE approach were used for the assessment of the risk of bias and quality of evidence (QE). Results In the quantitative synthesis 16 trials were included, using MARS®, Prometheus®, ELAD®, plasma exchange (PE) and BioLogic-DT®. Overall (OS) and transplant-free (TFS) survival were assessed at 1 and 3 months. PE significantly improved 3-month OS compared to SMT (RR 0.74, CrI: 0.6–0.94) and ranked first on the cumulative ranking curves for both OS outcomes (SUCRA: 86% at 3 months; 77% at 1 month) and 3-month TFS (SUCRA: 87%) and second after ELAD for 1-month TFS (SUCRA: 76%). Other comparisons did not reach statistical significance. QE was moderate for PE concerning 1-month OS and both TFS outcomes. Other results were of very low certainty. Conclusion PE seems to be the best currently available liver support therapy in ACLF regarding 3-month OS. Based on the low QE, randomized trials are needed to confirm our findings for already existing options and to introduce new devices.

Sign in / Sign up

Export Citation Format

Share Document