Management of cancer-related vertebral compression fracture: Comparison of treatment options: A literature meta-analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20529-e20529
Author(s):  
A. Bhargava ◽  
D. Trivedi ◽  
L. Kalva ◽  
M. Tumas ◽  
M. Hooks ◽  
...  

e20529 Objective: The objective of this review was to compare the efficacy and safety of treatment options for management of vertebral compression fractures (VCF) secondary to multiple myeloma and/or metastatic tumors based on a meta-analysis of the literature. Methods: A search was performed of published literature through November 2008. All articles reporting at least one clinical outcome were included. VAS pain scores and cement extravasation were the most common efficacy and safety outcomes reported in the included studies and were considered for analysis. The mean weighted difference in VAS scores or the effect size was calculated using the number of patients in each study as the weights. The paired t-test was used to assess significance of these differences. A 95% confidence interval (CI) was computed around these differences. The significance of difference (VAS and % cement extravasations) between different modes of treatment was assessed using a two sample t-test. Results: A total of 59 studies met the inclusion criteria and were included in the meta-analysis. The majority of the included studies (56 studies) were case series. No randomized controlled study was identified. The total sample size from the included study was 4,460 patients - 73% of patients had a diagnosis of tumor metastasis to the vertebral column; 18% had a diagnosis of multiple myeloma. Percutaneous vertebroplasty (VP) was described in 57.6% studies; balloon kyphoplasty (BKP) in 20.3%; conservative/combined (CC) therapy in 22%. Results are shown in the Table . Conclusions: This meta-analysis indicates that BKP is more effective than either VP or conservative therapy in relieving pain secondary to cancer-related VCF and that BKP is a safer intervention than VP based on the analysis of the rates of cement extravasation. [Table: see text] No significant financial relationships to disclose.

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 20-21
Author(s):  
Ahmad Iftikhar ◽  
Muhammad Ashar Ali ◽  
Anum Javaid ◽  
Muhammad Abu Zar ◽  
Atif Sohail ◽  
...  

Background: Multiple myeloma (MM) is an incurable disease, and clinical trials with newer agents have shown improved patient outcomes. There is a need for effective and tolerable treatment for patients with relapsed/refractory MM (RRMM). Proteasome inhibitors (bortezomib, carfilzomib, ixazomib) remain an integral part of regimens used in RRMM or newly diagnosed (ND) MM. This meta-analysis aims to assess the efficacy and safety of ixazomib (Ixa) based regimens in RRMM. Methods: A comprehensive literature search was performed on PubMed, Cochrane, Embase, Web of Science, and clinicaltrials.gov. We used MeSH and Emtree terms, "ixazomib" AND "multiple myeloma" from the inception of literature till 06/01/2020. We screened 1529 articles and included 3 randomized clinical trials (RCT, N=907) and 8 non-randomized clinical trials (NRCT, N=321). We excluded case reports, case series, review articles, meta-analysis, observational studies, and clinical trials that didn't provide data about the efficacy and safety of Ixa in RRMM. We used the R programming language (version 4.0.2) to conduct a meta-analysis. Results: In 11 clinical trials (N=1228), the age range of patients was 30-91 years. In Phase III RCTs (N=837) comparing Ixa + Lenalidomide (Len) + dexamethasone (Dex) vs. placebo + Len + Dex, risk ratio of overall response rate (ORR), complete response (CR), and very good partial response (VGPR) were 1.14 (95% CI=1.05-1.24, I2=80%), 1.87 (95% CI=1.17-2.99, I2=0), and 1.15 (95% CI=0.95-1.40, I2=0), respectively in favor of Ixa + Len + Dex. (Fig 1-3) Grade 3 or higher treatment-related adverse events (TRAEs) thrombocytopenia, diarrhea, and rash were reported in 20%, 5.7% and 6.4% of the patients in the Ixa group vs. 10%, 2.1%, and 2.8% in the placebo group, respectively. In a Phase II RCT by Kumar et al (N=70) comparing the Ixa dosage, 4 mg Ixa + Dex yielded an ORR of 31%, CR 2.8%, and VGPR 17.1%, while 5.5 mg Ixa yielded improved ORR of 54%, CR 2.8%, and VGPR 25.7%. In a NRCT by Costello et al. (N=6), Ixa + daratumumab (Dara) + Pom + Dex yielded 100% ORR, CR 5% (95% CI=0.17-0.83), and VGPR 50% (95% CI=0.17-0.83). ≥Grade 3 TRAEs were hypertension (16%), and hematological (33%). Among 417 patients from two RCT in single arm who received Ixa + Len + Dex, pooled ORR was 70% (95% CI=0.53-0.82, I2=84%), pooled CR 11% (95% CI=0.8-0.14, I2=0), and pooled VGPR was 29% (95% CI=0.18-0.43, I2=66%). In a NRCT by Dhakal et al. (N=19), Ixa + bendamustine + Dex yielded an ORR 58% (95% CI=0.36-0.77), CR 0, and VGPR 11% (95% CI =0.03-0.34). ≥Grade 3 TRAEs were neutropenia 31%, thrombocytopenia 52%, and diarrhea 10%. In 2 NRCT (N=106), Ixa + cyclophosphamide (Cyc) + Dex yielded a pooled ORR 52% (95% CI=0.42-0.61, I2=0), CR 4% (95% CI=0.01-0.10, I2=0), and VGPR 17% (95% CI=0.11-0.25, I2=0). ≥Grade 3 TRAEs were thrombocytopenia (15%), and upper abdominal pain (4%). In a NRCT by Ludwig et al. (N=90), Ixa + thalidomide (Thal) + Dex yielded an ORR 51% (95% CI=0.41-0.61), CR 9% (95% CI=0.5-0.17), and VGPR 14% (95% CI=0.09-0.23). ≥Grade 3 TRAEs were anemia (17.8%), and infections (16.1%). In a NRCT by Krishnan et al. (N=31), Ixa + Pomalidomide (Pom) + Dex yielded an ORR 48% (95% CI=0.32-0.65) and VGPR 16% (95% CI=0.07-0.33). (Fig 4-6) ≥Grade 3 TRAEs were neutropenia (10%), and lymphopenia (35%). In 2 NRCT by Kumar et al. (N=70) of two drugs combination, Ixa + Dex yielded a pooled ORR 43% (95% CI=0.28-0.59, I2=47%), pooled CR 1% (95% CI=0-0.09, I2=0), and pooled VGPR 24% (95% CI=0.16-0.36, I2=0). ≥Grade 3 TRAEs were hematological (28%), and non-hematological (22.8%). In 2 NRCT of Ixa monotherapy (N=69), pooled ORR was 17% (95% CI=0.10-0.28, I2=0), and pooled CR 6% (95% CI=0.2-0.22, I2=0). (Fig 4-6) ≥Grade 3 TRAEs were anemia (11%), thrombocytopenia (5.4%), and neutropenia (2.7%). Conclusion: Our study provides useful insight into relative efficacy of various Ixa regimens for the treatment of RRMM. The pooled analysis of RCT showed that the combination of Ixa + Len + Dex yielded better response as compared to placebo. In the pooled analysis of outcomes in single arm NRCT, Ixa + Dara + Pom + Dex and Ixa + Len + Dex showed better efficacy outcomes as compared to Ixa + Dex in combination with Thal, Cyc, or Bendamustin. Three drugs Ixa combination regimens had better efficacy as compared to two drugs combination of Ixa + Dex and Ixa monotherapy. Ixa was well tolerated with acceptable safety profile. Additional multicenter, double-blind clinical trials are needed to confirm these results. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S787-S787
Author(s):  
Tim Reason ◽  
Karan Gill ◽  
Christopher Longshaw ◽  
Rachael McCool ◽  
Katy Wilson ◽  
...  

Abstract Background Antimicrobial resistance is a major and growing threat to global public health. Cefiderocol (CFDC) is a new siderophore-cephalosporin with a wide activity spectrum covering all aerobic GN pathogens including all WHO critical priority pathogens, that was recently approved by FDA for the treatment of GN cUTI in susceptible organisms. We aim to understand the relative efficacy and safety of current treatment options for cUTI caused by MDR GN pathogens. Methods We conducted a systematic review to identify all relevant trials that investigated the efficacy and safety of antimicrobial regimens, for the treatment of GN pathogens in cUTI. Outcomes of interest included clinical cure and microbiological eradication (ME) at time of cure (TOC) and sustained follow up (SFU), and safety. Evidence networks were constructed using data for outcomes of interest and analyses were conducted in a frequentist framework using NMA methods outlined by the NICE decision support unit using the netmeta package in R. Results A total of 5 studies, 6 interventions and 2,349 randomised patients were included in the final analysis. Interventions included CFDC, imipenem-cilastatin (IPM-CIL), ceftazidime-avibactam (CAZ/AVI), doripenem (DOR), levofloxacin and ceftolozane-tazobactam (CEF/TAZ). Trials included predominantly Enterobacterales, and Pseudomonas aeruginosa and very few Acinetobacter baumannii. The patient population presented some clinical differences across trials, which were not adjusted for the NMA. Overall, there were numerical differences (especially in endpoints at SFU favouring CFDC), but all treatments showed similar efficacy and safety, with exception of higher ME rate at TOC for CFDC vs IPM, Table 1, also observed at SFU, consistent with the data from the individual clinical trial. Table 1- Results for microbiological eradication Table 1- Results for microbiological eradication Conclusion This NMA, showed superiority of CFDC vs IPM-CIL in ME at TOC and SFU and similar efficacy and safety vs all other comparators, with numeric differences favouring CFDC for outcomes at SFU. These traditional methodologies for NMA, are only valid within a similar pathogens pool and population across the trials, and may not reflect the full value of breadth of coverage that new therapeutic options bring for the treatment of MDR GN pathogens. Disclosures Tim Reason, PhD, Shionogi (Consultant) Karan Gill, MSc, Shionogi BV (Employee) Christopher Longshaw, PhD, Shionogi B.V. (Employee) Rachael McCool, PhD, York Health Economics Consortium (Employee, YHEC was commissioned by Shionogi to conduct the systematic review) Katy Wilson, PhD, York Health Economics Consortium (Employee, Shionogi commissioned YHEC to conduct the systematic review) Sara Lopes, PharmD, Shionogi BV (Employee)


2021 ◽  
Vol 49 (8) ◽  
pp. 030006052110381
Author(s):  
Yin Wang ◽  
Yanqing Li ◽  
Ye Chai

Objective To systematically evaluate the efficacy and safety of combination regimens containing daratumumab in patients with multiple myeloma (MM). Methods A systematic search of publications listed on electronic databases (PubMed®, The Cochrane Library, Science Direct and Web of Science) between inception and 13 November 2020 was conducted to find randomized controlled trials (RCTs) that included patients with MM that were treated with combination regimens containing daratumumab. Results A total of seven RCTs were included ( n = 4268 patients). Meta-analysis showed that compared with the control group, the group containing daratumumab showed a significantly better overall response rate and a complete response or better. Daratumumab improved efficacy in both standard-risk and cytogenetically high-risk patients with MM. The prevalence of neutropenia (≥grade 3) and pneumonia was significantly higher in the daratumumab group compared with the control group. Conclusion The available evidence demonstrated that the clinical application of combination regimens containing daratumumab improved the efficacy in patients with MM and had acceptable safety.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20015-e20015
Author(s):  
Kihyun Kim ◽  
Chang Ki Min ◽  
Youngil Koh ◽  
Kenichi Ishizawa ◽  
Sung-Hyun Kim ◽  
...  

e20015 Background: The Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) plus carfilzomib and dexamethasone (Kd) significantly improved progression-free survival (PFS) compared with Kd in patients (pts) with relapsed multiple myeloma (RMM) (hazard ratio [HR] 0.53; 99% confidence interval [CI] 0.32–0.89; P= 0.0007). We evaluated the efficacy and safety of Isa-Kd in the East Asian patients (19 Japanese, 27 Korean). Methods: RMM pts who received 1-3 prior lines of therapy were stratified to receive Isa-Kd or Kd. Isa-Kd arm received Isa (10 mg/kg intravenously) weekly for 4 weeks, then every 2 weeks. Both arms received K (20 mg/m2 days 1-2, 56 mg/m2 thereafter) twice-weekly for 3 of 4 weeks, and d (20 mg) twice-weekly. Treatment continued until disease progression or unacceptable adverse events (AE). The primary endpoint was prolongation of PFS. Key secondary endpoints included; very good partial response or better (≥VGPR), complete response (CR) rate and minimal residual disease negativity (MRD–) rate. Results: East Asian pts (25 Isa-Kd, 21 Kd) were randomized. Pt characteristics were similar in the East Asian subgroup compared with the intent to treat (ITT) population (N = 302). Median age (Isa-Kd 64.0 [range 45–83] years vs Kd 60.0 [range 33–73] years); median prior lines Isa-Kd 2.0 (range 1–3) vs Kd 1.0 (range 1–3); refractory to lenalidomide 16.0% Isa-Kd vs 47.6% Kd; refractory to PI 20.0% Isa-Kd vs 33.3% Kd; high-risk cytogenetics 48.0% Isa-Kd vs 42.9% Kd. After a median follow-up of 20.7 months, the addition of Isa to Kd improved ≥VGPR, CR and MRD– rates (Table). The HR 0.64 (95%CI: 0.231-1.764) for disease progression or death favored Isa-Kd. Grade ≥3 AEs were observed in 79.2% Isa-Kd vs 55.0% Kd pts, serious TEAEs in 45.8% Isa-Kd vs 50.0% Kd; TEAEs leading to treatment discontinuation were lower in the Isa-Kd group (4.2% Isa-Kd vs 10.0% Kd). Overall, 64.0% Isa-Kd vs 42.9% Kd pts were still receiving treatment. Conclusions: Efficacy and safety results of Isa-Kd in East Asian pts are consistent with the results of the overall IKEMA population, in which significantly better efficacy (PFS, CR, ≥VGPR and MRD– rate) was reported in favor of Isa-Kd without an increase in the number of patients with serious TEAEs or discontinuations. Isa-Kd is a potential treatment option for East Asian pts with RMM. Clinical trial information: NCT03275285. [Table: see text]


BMJ Open ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. e035346
Author(s):  
Yuchen He ◽  
Hongyi He ◽  
Dong-Xing Xie ◽  
Xiaoxiao Li ◽  
Yilun Wang

IntroductionMost of the patients who received arthroscopic knee surgery will suffer moderate to severe pain, which can delay the rehabilitation process and increase the risk of postoperative complications. Therefore, seeking a safe and effective postoperative analgesia is necessary for promoting the application of arthroscopic surgery. This protocol aims to detail a planned systematic review and meta-analysis on the comparative efficacy and safety of single-dose intra-articular injection of analgesics for pain relief after knee arthroscopy.Method and analysisPubMed, Embase, Web of Science and Cochrane Library will be searched from inception to 1 June 2020 to retrieve randomised controlled trials (RCTs) that compared the commonly used single-dose intra-articular analgesics (ie, morphine; bupivacaine (including levobupivacaine); ropivacaine and magnesium alone or in combination) with placebo or between each other for postoperative pain relief among patients who had received knee arthroscopy. The primary outcome is pain intensity at 2-hour and 24-hour postoperatively; the secondary outcomes include side effects (eg, knee effusion, nausea, vomiting and flushing), the number of patients requiring supplementary analgesia and the time to first analgesic request. The methodological quality of the included RCTs will be assessed based on the Cochrane risk of bias table. The Bayesian network meta-analysis will be conducted using WinBUGS V.1.4.3.Ethics and disseminationSince no private or confidential patient data will be contained in the reporting, approval from an ethics committee is not required. Our study raises no ethical issue, and the results will be published in a peer-reviewed journal.PROSPERO registration numberCRD42019130876.


2020 ◽  
Vol 11 (8) ◽  
pp. 1285-1292 ◽  
Author(s):  
Smith Giri ◽  
Madan Raj Aryal ◽  
Han Yu ◽  
Alyssa Grimshaw ◽  
Ranjan Pathak ◽  
...  

2019 ◽  
Vol 13 (5) ◽  
pp. 372-377 ◽  
Author(s):  
Daniel J. Scott ◽  
John Steele ◽  
Amanda Fletcher ◽  
Selene G. Parekh

Background. Patients with talar avascular necrosis (AVN) have limited treatment options to manage their symptoms. Historically, surgical options have been limited and can leave patients with little ankle motion and have high failure rates. The use of custom 3D printed total talar replacements (TTRs) has arisen as a treatment option for these patients, possibly allowing better preservation of hindfoot motion. We hypothesized that patients undergoing TTR will demonstrate a statistically significant improvement in Foot and Ankle Outcome Score (FAOS) at 1 year after surgery. Methods. We retrospectively reviewed 15 patients who underwent a TTR over a 2-year period. Patient outcomes were reviewed, including age, sex, comorbidities, etiology of talar pathology, number and type of prior surgeries, radiographic alignment, FAOS and Visual Analog Scale (VAS) score, and range of motion. Data analysis was performed with Student t-tests and multivariate regression. Results. FAOSs and VAS scores showed statistically significant improvements postoperatively as compared with preoperative scores. There was a statistically significant decrease in VAS pain scores from 7.0 preoperatively to 3.6 (P < .001). Average follow-up was 12.8 months. With the number of patients available, there was no statistically significant change in radiographic alignment parameters postoperatively as compared with preoperatively (P values ranged from .225 to .617). Conclusion. Our hypothesis that these patients show statistically significant improvements in FAOSs at 1 year was confirmed. TTR represents an exciting treatment option for patients with talar AVN, though longer-term follow-up is needed. Level of Evidence: Level IV: Case series


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3477-3477
Author(s):  
Yucai Wang ◽  
Fang Yang ◽  
Wenwen Zhang ◽  
Xiaoxiang Guan ◽  
Neil Kothari ◽  
...  

Abstract Objective: To evaluate the efficacy and safety of immunomodulatory drugs (IMiDs) in maintenance therapy of multiple myeloma through meta-analysis of randomized controlled trials (RCTs). Patients and methods: PubMed, Web of Science, ASCO, ESMO and ASH databases were searched for RCTs that investigated the treatment outcomes (overall survival [OS], progression-free survival [PFS] and/or event-free survival [EFS] and/or time to progression [TTP]) of maintenance therapy with IMiDs in patients with multiple myeloma. Study endpoints included OS, PFS/EFS/TTP, and grade 3 or 4 adverse events. Pooled hazard ratios (HRs) for survival outcomes and risk ratios (RRs) for dichotomous data with 95% confidence interval (CI) were calculated using Comprehensive MetaAnalysis (v2). The random-effect model was utilized in view of clinical heterogeneity in the study population. Results: Eighteen RCTs comprising a total of 6562 patients were included in this meta-analysis. IMiDs used in the RCTs included thalidomide (14 trials) and lenalidomide (4 trials). Overall, IMiD-based maintenance therapy significantly improved OS (HR = 0.91, 95% CI = 0.84 - 0.99, P = 0.027) and PFS (HR = 0.63, 95% CI = 0.60 - 0.68, P < 0.001). Notably, IMiDs maintenance therapy increased OS in the setting of ASCT but showed no OS prolongation without ASCT. On further stratification, thalidomide-based maintenance therapy demonstrated OS benefit only in the setting of ASCT, while lenalidomide-based maintenance therapy did not show OS benefit regardless of transplantation status. For PFS however, both thalidomide- and lenalidomide-based maintenance therapies demonstrated significant survival benefits, regardless of transplantation status (Table 1). IMiD-based maintenance therapy increased the risk of developing grade 3 or 4 neutropenia (RR = 3.04, 95% CI = 2.49 - 3.70, P < 0.001), thrombocytopenia (RR = 2.68, 95% CI = 1.90 - 3.79, P < 0.001), anemia (RR = 1.97, 95% CI = 1.23 - 3.15, P = 0.005), infection (RR = 1.53, 95% CI = 1.22 - 1.92, P < 0.001), fatigue (HR = 1.71, 95% CI = 1.24 - 2.36, P = 0.001), constipation (RR = 2.04, 95% CI = 1.15 - 3.62, P = 0.015), and peripheral neuropathy (RR = 2.02, 95% CI = 1.20 - 3.39, P = 0.008). Conclusions: IMiD-based maintenance therapy results in significant improvement in OS and PFS in multiple myeloma patients but increased the risk of developing some grade 3 or 4 adverse events. While thalidomide-containing maintenance therapy regimens showed OS benefits in the setting of ASCT, lenalidomide-containing maintenance therapy did not prolong OS regardless of transplantation status. Both thalidomide- and lenalidomide-based maintenance therapies increased PFS in multiple myeloma patients independent of transplantation status. When more data on lenalidomide and the newer agent pomalidomide become available, further analysis will be warranted to analyze the efficacy and safety of IMiDs in multiple myeloma maintenance therapy. Table 1. Effects of IMiD-based maintenance therapy on OS and PFS in multiple myeloma patients IMiD ASCT status Survival Number of trials HR 95% CI P value Thalidomide/Lenalidomide combined OS 18 0.91 0.84 - 0.99 0.027 with ASCT OS 10 0.88 0.78 - 0.99 0.036 without ASCT OS 9 0.94 0.83 - 1.06 0.299 Thalidomide combined OS 14 0.92 0.84 - 1.01 0.090 with ASCT OS 8 0.87 0.77 - 1.00 0.049 without ASCT OS 7 0.97 0.85 - 1.10 0.640 Lenalidomide combined OS 4 0.84 0.67 - 1.04 0.102 with ASCT OS 2 0.89 0.66 - 1.20 0.457 without ASCT OS 2 0.78 0.57 - 1.06 0.114 Thalidomide/Lenalidomide combined PFS 17 0.63 0.60 -0.68 < 0.001 with ASCT PFS 9 0.62 0.57 - 0.67 < 0.001 without ASCT PFS 9 0.66 0.60 - 0.73 < 0.001 Thalidomide combined PFS 13 0.67 0.63 - 0.72 < 0.001 with ASCT PFS 7 0.66 0.60 - 0.72 < 0.001 without ASCT PFS 7 0.69 0.62 -0.77 < 0.001 Lenalidomide combined PFS 4 0.50 0.43 - 0.58 < 0.001 with ASCT PFS 2 0.49 0.41 - 0.58 < 0.001 without ASCT PFS 2 0.52 0.40 - 0.67 < 0.001 Disclosures No relevant conflicts of interest to declare.


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