scholarly journals The Prognostic Impact of Abnormal Protein Bands in Multiple Myeloma: A Systematic Review and Meta-Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4738-4738
Author(s):  
Soon Khai Low ◽  
Matthew Ho ◽  
Saad Jamshed
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Complete Response ◽  
Oligoclonal Bands ◽  
Prognostic Impact ◽  
Free Survival ◽  
Abnormal Protein ◽  
Statistical Heterogeneity

Abstract Introduction: The detection of abnormal protein bands (APB) different from the original monoclonal protein in patients with multiple myeloma (MM) who underwent stem cell transplantation and/or chemotherapy has been reported. These atypical serum immunofixation patterns may be monoclonal (also termed secondary monoclonal gammopathy of undetermined significance) or oligoclonal bands (OB). The prognostic significance of this phenomenon remains controversial. This systematic review and meta-analysis aimed to summarize and analyze the evidence for the association between APB with survival in MM patients. Methods: A systematic search of PubMed, Cochrane, Google Scholar, Medline-Ovid, CINAHL, and ERIC, was conducted using relevant search terms. All studies were screened using predefined selection criteria and critically appraised for quality assessment following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. All studies that described the presence of APB, defined as monoclonal spike with heavy or light chain immunoglobulin distinct from the original paraprotein at initial diagnosis of MM, and its associations with survival were included. Studies that reported multivariate adjusted hazard ratios (HR) were further included for meta-analysis. Random-effects model was used to synthesize the pooled HR estimate for the association of APB with survival. Cochran's Q statistics and I2 tests were used to evaluate statistical heterogeneity. Results: A total of 24 out of 181 eligible studies were included for qualitative synthesis. Four studies (including 1115 patients) that reported HR estimates were included in the final meta-analysis. The random-effect summary HR for the progression-free survival among patients with APB was 0.44 (95% CI, 0.31-0.65) with no statistical heterogeneity (I2=0%, p=0.93). The pooled HR for the association with overall survival was 0.31 (95% CI, 0.14-0.66) with moderate statistical heterogeneity (I2=45%; p=0.16) for patients with APB. One study (Silva et al, 2017) only included patients with at least very good partial response while the other three studies reported similar findings of higher occurrence of APB with complete response (Tovar et al, 2013; Jo et al, 2014; Zou et al, 2014). These results are also consistent with the presumed association of APB with complete response as suggested in other studies included in qualitative review. Conclusions: This study indicated a potential prognostic value of APB for favorable outcomes in the context of both overall and progression-free survival in MM patients after treatment. Further research is needed to evaluate the prognostic impact of the sole emergence of APB irrespective of treatment response. Figure 1 Figure 1. Disclosures Jamshed: Takeda: Honoraria.

Efficacy Of Bortezomib-Based Regimens With Or Without An Immunomodulatory Agent In Older Adults With Multiple Myeloma: A Systematic Review and Meta-Analysis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5580-5580
Author(s):  
Jordan Atkins ◽  
Susan A Fowler ◽  
Methodius Tuuli ◽  
Aimee S James ◽  
Tanya M Wildes
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Overall Survival ◽  
Partial Response ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Complete Response ◽  
Inclusion Criteria ◽  
Free Survival ◽  
Good Partial Response

Abstract Introduction Multiple myeloma (MM) is an incurable disease within older adults, caused by the malignant proliferation of plasma cells and destruction of skeletal structure, with subsequent end-organ dysfunction. In the elderly and transplant ineligible population, chemotherapeutic regimens that include novel and conventional drugs are currently being employed to attain optimal response and survival outcomes. We performed a systematic review and meta-analysis to investigate the efficacy of the proteasome inhibitor bortezomib, in combination with an immunomodulatory drug (IMiD) versus bortezomib-containing regimens alone in improving overall survival, progression-free survival, and response in patients aged 65 and older ineligible for stem cell transplant. Methods We searched Pubmed/Medline, Embase, Scopus, CENTRAL, DARE, and clinicaltrials.gov databases for randomized controlled trials (RCTs) published from January 1946 until March 2013 using search terms such as: “bortezomib” “thalidomide/analogs and derivatives” and “lenalidomide.” Primary outcomes such as overall survival “OS” and progression-free survival “PFS” were harvested from standard indexes and on-topic articles. We abstracted data from relevant studies for analysis. Heterogeneity was assessed using Cochrane's Q and Higgin's I2 with p<0.1 considered significant. Pooled risk ratios (RR) and hazard ratios (HR) were estimated using DerSimonain and Laird random effect models. Results We identified 762 studies, 201 of which were duplicates that were excluded. Of these studies, 561 met initial inclusion criteria. After screening and systematic review, we found a majority of the articles originated from sub-analyses or reviews of 2 major studies which fully met inclusion criteria: 1) bortezomib-melphalan-prednisone-thalidomide (VMPT) versus bortezomib-melphalan-prednisone (VMP) [Palumbo JCO 2010] and 2) bortezomib-thalidomide-prednisone (VTP) versus VMP [Mateos Lancet Onc 2010). Of the two studies included, 384 patients received thalidomide and bortezomib-containing regimens (VMPT or VTP), and 387 patients received VMP. Thalidomide-containing combinations were associated with improvement in complete response (pooled RR 1.55 [95% Confidence intervals 1.23-1.95]) and very good partial response (pooled RR 1.19 [95% Confidence intervals 1.04-1.38]). There was no evidence of significant heterogeneity associated with either of these outcomes across the studies (I2=0; p=0.559 and I2=0; p=0.600). There were no significant differences in partial response (pooled RR 1.08; 95% CI 0.98-1.19), overall survival (pooled HR 1.04; 95% CI 0.65-1.44), or progression-free survival (pooled HR 0.91; 95% CI 0.29-1.42). There were also no significant differences in toxic side effects (Table). Conclusion Based on the limited data included in this meta-analysis, we found that the addition of thalidomide to a bortezomib-based regimen was associated with improved complete response and very good partial response, but no improvement in overall or progression-free survival. Larger studies of thalidomide and other immunomodulatory agents are required to further clarify the role of adding IMiDs to bortezomib-based regimens in the treatment of MM. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Systematic review and meta-analysis of docetaxel perioperative chemotherapy regimens in gastric and esophagogastric tumors

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Pedro Luiz Serrano Uson Junior ◽  
Vanessa Montes Santos ◽  
Diogo Diniz Gomes Bugano ◽  
Elivane da Silva Victor ◽  
Edna Terezinha Rother ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Complete Response ◽  
Significant Heterogeneity ◽  
Free Survival ◽  
Dose Ranging ◽  
Prospective Trials ◽  
Grade 3 ◽  
One Year

Abstract FLOT regimen became the standard perioperative treatment in several centers around the world for esophagogastric tumors despite concerns about toxicity. In addition, FLOT has never been compared with other docetaxel-based regimens. To address this question, we conducted a systematic review of PubMed, Embase and Web of Science including prospective or retrospective studies of docetaxel based perioperative regimen in gastric and esophagogastric tumors. Data regarding chemotherapy regimens, efficacy and toxicity were extracted. Outcomes were compared using a random effects model. Of 548 abstracts, 16 were considered eligible. Comparing the studies with meta-analysis we can see that the regimens are similar in terms of pathological complete response, resection rate, progression free survival and overall survival in one year, without significant heterogeneity. The meta-regression of docetaxel dose failed to show any association with dose ranging between 120–450 mg/m². Regarding the toxicity of the regimens it is noted that the regimens are quite toxic (up to 50–70% of grade 3–4 neutropenia). The results of this meta-analysis with a combined sample size of more than 1,000 patients suggest that docetaxel perioperative regimens are equivalent in outcomes. Prospective trials addressing modified regimens should be performed to provide less toxic strategies and be applicable to all patients.

The role of complete response in multiple myeloma

Blood ◽  
2009 ◽  
Vol 114 (15) ◽  
pp. 3139-3146 ◽  
Author(s):  
Jean-Luc Harousseau ◽  
Michel Attal ◽  
Herve Avet-Loiseau
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Dose ◽  
Prognostic Impact ◽  
Free Survival ◽  
Depth Of Response ◽  
The Impact ◽  
Good Partial Response

AbstractIn multiple myeloma (MM), the impact of complete response (CR) could be shown only after introduction of high-dose therapy plus autologous stem cell transplantation (ASCT). In the context of ASCT, achieving CR (negative immunofixation and normal bone marrow) or at least very good partial response is associated with longer progression-free survival and in most studies longer survival. With novel agents, high CR rates are achieved and this prognostic impact of CR is being shown as well, both in relapsed and in newly diagnosed MM. However the benefit of CR achievement depends on the type of treatment and is not identical for all patients. In elderly patients, treatments inducing more CR may be more toxic. Although CR achievement is necessary in patients with poor-risk disease, it might not be as critical for long survival in more indolent MM. CR achievement is not the only objective of treatment because it is possible to further improve the depth of response and the outcome by continuing treatment after CR achievement. Finally, there are several levels of CR and in the future it will be necessary to confirm the prognostic impact of immunophenotypic or molecular CR or of CR defined by imaging procedures.

scholarly journals Prognostic Impact of Memory CD8(+) T Cells on Immunotherapy in Human Cancers: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Yao Jin ◽  
Aili Tan ◽  
Jia Feng ◽  
Zexi Xu ◽  
Peiwei Wang ◽  
...  
Keyword(s):  
Systematic Review ◽  
T Cells ◽  
Cancer Patients ◽  
Cd8 T Cells ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Prognostic Impact ◽  
Free Survival ◽  
Memory Cd8 T Cells

ObjectiveThe objective of this systematic review and meta-analysis was to determine the prognostic value of memory CD8(+) T cells in cancer patients with immunotherapy.MethodsEMBASE, MEDLINE (PubMed), and Web of Science databases were searched to identify suitabile articles published before March 2021. Risk of bias on the study level was assessed using the Cochrane Bias Risk Assessment Tool. The hazard ratios (HRs) and 95% confidence intervals (CIs) of pooled progression-free survival (PFS) and overall survival (OS) were calculated using RevMan 5.4 to evaluate the prognostic impact of memory CD8(+) T cells.ResultsIn total, nine studies were included in the final analysis. High levels of memory CD8(+) T cells were significantly closely correlated with better progression-free survival (PFS) and overall survival (OS) of cancer patients with immunotherapy (PFS, HR 0.64, 95% CI 0.53–0.78; OS, HR 0.37, 95% CI 0.21–0.65). Memory CD8(+) T cells still have significant prognostic value in cancer patients given immunotherapy alone after excluding of other interfering factors such as chemotherapy, radiotherapy, and targeted therapy (PFS, HR 0.65, 95% CI 0.48–0.89; OS, HR 0.23, 95% CI 0.13–0.42). However, high memory CD8(+) T cells levels did not correspond to a longer PFS or OS in cancer patients with non-immunotherapy (PFS, HR 1.05, 95% CI 0.63–1.73; OS, HR 1.29, 95% CI 0.48–3.48). Thus, memory CD8(+) T cells might be a promising predictor in cancer patients with immunotherapy.ConclusionsThe host’s overall immune status, and not only the tumor itself, should be considered to predict the efficacy of immunotherapy in cancer patients. This study is the first to show the significant prognostic value of memory CD8(+) T cells in immunotherapy of cancer patients through systematic review and meta-analysis. Thus, the detection of memory CD8(+) T cells has a considerable value in clinical practice in cancer patients with immunotherapy. Memory CD8(+) T cells may be promising immunotherapy targets.

scholarly journals The Prognostic Value of CD206 in Solid Malignancies: A Systematic Review and Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3422
Author(s):  
Jens M. Debacker ◽  
Odrade Gondry ◽  
Tony Lahoutte ◽  
Marleen Keyaerts ◽  
Wouter Huvenne
Keyword(s):  
Systematic Review ◽  
Prognostic Value ◽  
Negative Impact ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Prognostic Impact ◽  
Free Survival ◽  
Meta Analyses ◽  
Tumor Types

An increased presence of CD206-expressing tumor associated macrophages in solid cancers was proposed to be associated with worse outcomes in multiple types of malignancies, but contradictory results are published. We performed a reproducible systematic review and meta-analysis to provide increased evidence to confirm or reject this hypothesis following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. The Embase, Web of Science, and MEDLINE-databases were systematically searched for eligible manuscripts. A total of 27 papers studying the prognostic impact of CD206 in 14 different tumor types were identified. Meta-analyses showed a significant impact on the overall survival (OS) and disease-free survival (DFS). While no significant differences were revealed in progression-free survival (PFS) and disease-specific survival (DSS), a shift towards negative survival was correlated with increased CD206-expresion. As a result of the different tumor types, large heterogeneity was present between the different tumor types. Subgroup analysis of hepatocellular carcinoma and gastric cancers revealed no heterogeneity, associated with a significant negative impact on OS in both groups. The current systematic review displays the increased presence CD206-expressing macrophages as a significant negative prognostic biomarker for both OS and DFS in patients diagnosed with solid cancers. Because a heterogenous group of tumor types was included in the meta-analysis, the results cannot be generalized. These results can, however, be used to further lead follow-up research to validate the specific prognostic value of CD206 in individual tumor types and therapeutic approaches.

Bendamustine for Patients with Indolent Lymphoma an Updated Meta-Analysis of Randomized Controlled Trials (RCT)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3963-3963
Author(s):  
Liat Vidal ◽  
Liat Shargian ◽  
Ofer Shpilberg ◽  
Ron Ram ◽  
Pia Raanani ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Complete Response ◽  
Advisory Board ◽  
Lymphocytic Leukemia ◽  
Indolent Lymphoma ◽  
Statistical Heterogeneity ◽  
Grade 3

Abstract Background In 2011 we performed a systematic review and meta-analysis evaluating the efficacy of bendamustine for patients with indolent lymphoproliferative malignancies. We included 5 trials. Since then several new trials of bendamustine for indolent lymphoproliferative malignancies were conducted, and some are still ongoing. Individual trials supported a progression free survival (PFS) benefit but none was powered to demonstrate an effect on overall survival (OS). In order to evaluate the effect of bendamustine on the OS of patients with indolent lymphoproliferative malignancies we performed a systematic review and meta-nalysis of RCTs. Methods We included RCTs that compared bendamustine to other chemotherapy regimens for patients with indolent lymphoproliferative malignancies including chronic lymphocytic leukemia (CLL). We included patients in both first line and the relapsed setting. In July 2015 we searched The CochraneLibrary, MEDLINE, conference proceedings, and databases of ongoing trials. Two reviewers appraised the quality of trials and extracted data.The primary outcome wasall cause mortality. Secondary outcomes included: PFS, complete response (CR), and adverse events. Relative risk (RR) with 95% confidence intervals (CIs) were estimated and pooled for dichotomous data and hazard ratio (HR) for time to event data. Results We identified 8 trials, conducted between the years 1994 and 2012 (one trial is ongoing) randomizing 2484 adult patients with a mean/median age of 58 - 74 years. The rate of patients with follicular lymphoma ranged between 40% to 70%, and mantle cell lymphoma 16% to 22% in the 3 trials that included patients with those types of lymphoma. Four trials included only patients with CLL. The comparisons were between bendamustine, vincristine, prednisone to cyclophosphamide, vincristine, prednisone (CVP); bendamustine-rituximab (BR) to cyclophosphamide, adriamycin, vincristine, prednisone, rituximab (RCHOP), RCVP; BR to fludarabine-rituximab and to fludarabine, cyclophosphamide, rituximab (FCR); and bendamustine to chlorambucil (+-rituximab). Bendamustine significantly reduced mortality risk of patients with indolent lymphoproliferative malignancies compared to control, RR for death 0.84; 95% CI 0.73 - 0.96, I2 = 0 (Figure). Including only CLL patients the RR is 0.84; 95% CI 0.69 - 1.03. PFS was improved with bendamustine in each of the trials and when trials were pooled, HR 0.55, 95% CI 0.41 - 0.74, I2 of heterogeneity 78%. The rate of CR improved with bendamustine compared to control for patients with indolent lymphoma, RR 1.40; 95% CI 1.09 - 1.81, random effects model, I2 = 46%. We did not pool results of CR of patients with CLL due to a high statistical heterogeneity. The rates of grade 3/4 infection or any grade 3/4 adverse events were not different between the arms. Discussion This meta-analysis shows that bendamustine decreases the risk of mortality of patients with indolent lymphoma and CLL compared to other chemotherapy. In addition, PFS is improved. Further analysis of results with longer follow up is expected. Disclosures Shpilberg: Gilead: Consultancy; Millennium Takeda: Consultancy. Raanani:Novartis: Other: Advisory Board, Research Funding; Ariad: Other: Advisory Board; BMS: Other: Advisory Board; Pfizer: Other: Advisory Board.

scholarly journals A Systematic Review and Network Meta-Analysis of Randomized Data on Efficacy of Novel Therapy Combinations in Patients with Lenalidomide Refractory Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-12
Author(s):  
Ghulam Rehman Mohyuddin ◽  
Jill Hampton ◽  
Muhammad Aziz ◽  
Sadik Khuder ◽  
Saad Ullah Malik ◽  
...  
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Controlled Trials ◽  
Significant Heterogeneity ◽  
Free Survival ◽  
Treatment Regimens ◽  
Randomized Controlled

Introduction: Advancements in the treatment of multiple myeloma (MM) with proteasome inhibitors [bortezomib (bort), carfilzomib (carf)], monoclonal antibodies [daratumumab (dara), isatuximab (isa) and elotozumab (elo)], and immunomodulatory drugs [IMiD) [lenalidomide and pomalidomide (pom)] have improved outcomes. However, using lenalidomide as frontline treatment and maintenance therapy exposes greater numbers of patients to lenalidomide prior to relapse. Consequently, the treatment of lenalidomide-refractory (LR) disease is an increasing area of concern. Given the lack of direct comparisons of different treatment regimens for LR MM, we used a systematic review to identify randomized controlled trials (RCTs) that included subgroup analysis of LR patients. The objective of our study was to compare the efficacy of novel treatment regimens in randomized trials for patients with LR MM using a network meta-analysis. Methods: Three databases were searched: MEDLINE/PubMed, Embase, and Cochrane Registry of Controlled Trials. All studies published between January 1, 2005 and December 30, 2019 were queried using keywords "multiple myeloma" and "randomized controlled trial". Only RCT's were included. Primary outcome was progression free survival (PFS) of patients enrolled in myeloma RCT's. Two independent investigators reviewed all the studies and resolved any conflict through mutual discussion. WNetwork meta-analysis using random-effects model was performed to generate direct and indirect comparisons between various treatment groups. Frequentist method was used to rank the interventions and P-score was generated. A higher P score (close to 1.00) corresponded to superior progression free survival. A P-value of &lt;0.05 was considered statistically significant. Hazard ratios (HR) with 95% confidence interval (CI) were calculated. I2statistic was used to assess heterogeneity between the studies as defined by the Cochrane Handbook for Systematic Reviews with a value &gt;50% considered as significant heterogeneity. We used 'R' (Bell Labs, Murray Hill, NJ, USA) for generating our statistical analysis and plots. Results: Our initial search strategy yielded 1171 results. After excluding duplicates, trials in progress, subset analysis and non-randomized studies, 123 RCTs were identified. Only 8 studies clearly reported outcomes of patients with LR myeloma and 7 studies (1698 patients) were included in final analysis of two discrete networks. Pom/bort/dex (HR: 0.65,95% CI: 0.50-0.84), dara/bort/dex (HR: 0.36, 95% CI: 0.21-0.63), and dara/carf/dex (HR: 0.38, 95% CI: 0.21-0.69) were all found to have improved PFS compared to bort/dex (Figure 2). These interventions were ranked as follows: Dara-bort-dex was the most efficacious with a P-score of 0.8758, followed by Dara/carf/Dex (P of 0.8514), Pom/bort/dex (P of 0.4791), Carf/dex (P of 0.2707) and Bort/dex (P of 0.0231). Within Network 2 (Figure 3), pom/dex (HR :0.50, 95% CI= 0.40-0.62), isa/pom/dex (HR: 0.30, 95% CI= 0.20-0.44) and elo/pom/dex (HR: 0.27, 95% CI=0.16-0.45), were all found to have improved PFS compared to dexamethasone (Figure 4). In Network 2, the ranking of interventions was as follows with Elo-pom-dex (P of 0.8716) the most efficacious, followed by Isa-pom-Dex (P of 0.7932) and Pom-dex (P of 0.3352). Conclusion: The results of our network meta-analysis of 1698 patients with lenalidomide refractory myeloma enrolled in seven randomized myeloma trials demonstrate that for lenalidomide refractory myeloma, triplet therapy is superior to doublet therapy. Regimens with the highest efficacy in this subset of patients were triplets containing monoclonal antibodies (such as dara/elo/isa). There is a need for further randomized data to better ascertain the best standard of care for these patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Efficacy and Safety of Novel Agent-Based Therapies for Multiple Myeloma: A Meta-Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Xiaoxue Wang ◽  
Yan Li ◽  
Xiaojing Yan
Keyword(s):  
Multiple Myeloma ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Complete Response ◽  
The Novel ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Agent Based ◽  
Randomized Controlled ◽  
Novel Agent

This study aimed at comparing bortezomib, thalidomide, and lenalidomide in patients with multiple myeloma (MM) for safety and efficacy using meta-analysis. This meta-analysis identified 17 randomized controlled trials (RCTs) including 6742 patients. These RCTs were separated according to the different agent-based regimens and to autologous stem-cell transplantation (ASCT). Complete response (CR), progression-free survival (PFS), overall survival (OS), and adverse events (AE) were combined. The total weighted risk ratio (RR) of CR was 3.29 [95% confidence interval (95% CI): 2.22–4.88] (P<0.0001) for the novel agent-based regimens. These novel agent-based regimens showed greater benefit in terms of PFS of all subgroups irrespective of whether the patient received ASCT or not. The hazard ratio (HR) for PFS was 0.64 [95% CI: 0.60–0.69] (P<0.00001). Improvements of OS could be found only in the bortezomib- and thalidomide-based regimens without ASCT. The pooled HRs were 0.74 [95% CI: 0.65–0.86] (P<0.0001) and 0.80 [95% CI: 0.70–0.90] (P=0.0004), respectively. Several AEs were shown more frequently in the novel agent-based regimens compared with controls such as hematologic events (neutropenia, anemia, and thrombocytopenia), gastrointestinal infection, peripheral neuropathy, thrombosis, and embolism events. In conclusion, in spite of the AEs, novel agent-based regimens are safe and effective for the treatment of MM.

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