Upfront treatment for newly diagnosed transplant-ineligible multiple myeloma patients: A systematic review and network meta-analysis of 14,533 patients over 29 randomized clinical trials

2019 ◽  
Vol 143 ◽  
pp. 102-116 ◽  
Author(s):  
Leo Sekine ◽  
Patrícia Klarmann Ziegelmann ◽  
Denise Manica ◽  
Carolina da Fonte Pithan ◽  
Monalisa Sosnoski ◽  
...  
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Newly Diagnosed

scholarly journals Ixazomib Based Regimens in Patients with Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis of Clinical Trials

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 35-35
Author(s):  
Anum Javaid ◽  
Faryal Razzaq ◽  
Muhammad Ashar Ali ◽  
Muhammad Abu Zar ◽  
Atif Sohail ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trial ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
Placebo Group ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Phase Ii Trial ◽  
Meta Analysis ◽  
Newly Diagnosed

Introduction: Multiple myeloma (MM) is an incurable malignancy, and clinical trials with newer agents have shown improved patient outcomes. Ixazomib (Ixa) is a proteasome inhibitor and induces apoptosis in cancer cells. It is commonly used with immunomodulators for the treatment of MM. We conducted a systematic review and meta-analysis to assess the efficacy of Ixazomib alone and in combination with other drugs for the treatment of newly diagnosed multiple myeloma (NDMM). Methods: A literature search was performed on PubMed, Cochrane, Embase, Web of Science, and clinicaltrials.gov. We used the following MeSH and Emtree terms; "ixazomib" AND "Multiple Myeloma" from inception till 06/05/2020. We screened 1,558 articles and included 3 randomized clinical trials (RCTs) (N=901) and 12 non-randomized clinical trials (NRCT) (N=632). We excluded case reports, case series, preclinical trials, review articles, observational studies, meta-analysis, and ongoing clinical trials that did not report interim efficacy outcomes. We used the R programming language (version 4.0.2) to conduct a meta-analysis. Results: In 15 clinical trials (N=1533), Ixa based regimens were used in patients with age range of 39-92 years. (Table 1) In 3 clinical trials (N=170), Ixa with Lenalidomide (Len) and dexamethasone (Dex) yielded a pooled overall response rate (ORR) of 90% (95% CI=0.82-0.94, I2=32%), a pooled complete response (CR) of 23% (95% CI=0.16-0.32, I2=24%) and a pooled ≥very good partial response and better (≥VGPR) of 39% (95% CI=0.24-0.57, I2 =76%) when used as induction therapy for NDMM patients. As consolidation therapy (N=88), pooled ORR was 91% (95% CI=0.79-0.97, I2=0), pooled CR was 36% (95% CI=0.27-0.47, I2=0) and pooled ≥VGPR was 70% (95% CI=0.53-0.84, I2=60%). (Fig 1-3) In 5 clinical trials (N=233), Ixa + cyclophosphamide (Cyc) + Dex yielded a pooled ORR, CR, and ≥VGPR of 76% (95% CI=0.70-0.81, I2 =0), 12% (95% CI=0.07-0.20, I2=44%), and 25% (95% CI=0.14-0.39, I2=78%), respectively. (Fig 1-3) The lower dose of Cyc 300mg/m2 had similar efficacy as 400mg/m2 with better safety profile in elderly patients. In a RCT (N=175) of Ixa with multiple combinations, Ixa + Dex yielded ORR 55% (95% CI=0.40-0.69), CR 14% (95% CI=0.07-0.28) and ≥VGPR 24% (95% CI=0.13-0.39). Ixa+ thalidomide (Thal) + Dex fostered ORR 82% (95% CI=0.70-0.90), CR 15% (95% CI=0.08-0.26), and VGPR 43% (95% CI=0.31-0.55). Ixa + bendamustine + Dex yielded ORR of 73% (95% CI=0.41-0.91), CR 9% (95% CI=0.01-0.44), and ≥VGPR 27% (95% CI=0.09-0.59). In one clinical trial (N=53), Ixa + melphalan (Mel) + prednisone (Pred) combination yielded pooled ORR, CR, and ≥VGPR of 66% (95% CI=0.52-0.77), 13% (95% CI=0.06-0.25), and 30% (95% CI=0.19-0.44), respectively. In a phase II trial (N=40), Ixa + daratumumab (Dara) + Len + Dex yielded an ORR, CR and ≥VGPR of 97% (95% CI=0.84-1), 15% (95% CI=0.07-0.28), and 35% (95% CI=0.22-0.51) respectively. (Fig 1-3) In a phase III RCT by Dimopholous et al. (N=656), Ixa maintenance therapy after stem cell transplant (SCT) yielded an ORR, CR, and ≥VGPR of 76%, 15%, and 54%, respectively. They observed 28% reduction in the risk of progression or death with Ixa vs. placebo, median progression free survival (mPFS) was 26.5 months (95% CI 23·7-33·8) vs 21·3 months [18·0-24·7]; hazard ratio 0·72, 95% CI 0·58-0·89; p=0·0023). Second malignancies were 3% in both ixazomib and placebo group. 27% of the patients in ixazomib group and 20% patients in placebo group experienced serious adverse events. In a clinical trial on unfit and frail patients (N=46) treated with Ixa + daratumumab (Dara) + Dex, pooled ORR and ≥VGPR were 83% (95% CI=0.69-0.91, I2=0), and 33% (95% CI=0.21-0.47, I2=0), respectively. (Fig 1-3) In the phase II trial, ORR, CR, and VGPR with ixazomib and lenalidomide were 64%, 26%, and 53%, respectively. Conclusion: Ixa in combination with Len, Dex, Cyc, Dara, Mel, Pred is effective in the treatment of NDMM patients. In early phase trials, Ixa with Dara, Len, and Dexa showed the highest overall response as induction therapy. Ixazomib maintainance therapy prolongs PFS after SCT as compared to placebo and represents an additional option for post SCT maintainace therapy in NDMM patiens. The safety profile of Ixa was acceptable with most commonly encountered adverse events were hematological including neutropenia and thrombocytopenia. Additional multicenter, double-blind, randomized 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.

scholarly journals Venous Thromboembolism with Contemporary Lenalidomide-Based Regimens and Adequate Thromboprophylaxis in Newly Diagnosed Multiple Myeloma: A Systemic Review and Meta-Analysis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4835-4835
Author(s):  
Rajshekhar Chakraborty ◽  
Saad Ullah Malik ◽  
Naimisha Marneni ◽  
Alex V. Mejia Garcia ◽  
Faiz Anwer ◽  
...  
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Phase I ◽  
Low Dose ◽  
Meta Analysis ◽  
Combination Regimen ◽  
Newly Diagnosed ◽  
Combination Regimens

Abstract Background: Lenalidomide (Len) and low-dose dexamethasone (dex) in combination with proteasome inhibitor (PI) or cytotoxic agent is an integral part of front-line therapy in multiple myeloma (MM). Use of Lenalidomide (Len) in MM had demonstrated an increased risk of venous thromboembolism (VTE) in initial studies which led to the incorporation of routine thromboprophylaxis with Len-based regimens. Existing estimate of VTE incidence from a prior analysis on Len-based regimens in newly diagnosed MM is 0.8 per 100 patient-cycles [Carrier et al. 2011]. However, there is a gap in literature on the incidence of VTE in patients receiving contemporary Len-based combination regimens along with adequate thromboprophylaxis. Hence, we conducted a systematic review and meta-analysis of clinical trials to assess the incidence of VTE with Len-based regimens in newly diagnosed MM patients. Method: We queried Ovid Medline, Ovid Embase and Cochrane Library databases to obtain relevant studies until March 2018. We included all phase I-III clinical trials testing a Len-based combination regimen for induction +/- consolidation therapy along with protocol-mandated thromboprophylaxis. VTE was defined as deep vein thrombosis or pulmonary embolism (CTCAE Grade 2 or above). Our primary outcome was pooled incidence of VTE events per patient-cycle, which was subsequently converted to VTE events per 100 patient-cycle for ease of comparison with existing literature in MM. We performed meta-analyses with random-effects model using a comprehensive meta-analysis software. Heterogeneity was calculated using I2 statistic and a value <25% was considered negligible, up to 50% moderate, and ≥70% was considered substantial heterogeneity. The protocol for this systematic review is registered with PROSPERO [CRD42018102971]. Results: Initial search generated 1069 citations. After screening, 15 clinical trials with 3381 patients were included. Among 15 trials, 4 were phase I/II, 6 were phase II and 5 were phase III. All but one trial used low-dose dex. The pooled incidence of VTE events was 0.4 per 100 patient-cycles [95% CI. 0.3-0.5; I2: 70%]. Incidence rate of VTE in individual studies are summarized in Table I. The Forest Plot is shown in Figure I. Subsequently, we performed pre-specified subgroup analyses on trials with Len-dex, Len-dex + PI, Len-dex + doxorubicin and Len with Melphalan-Prednisone (MPR). The pooled incidence of VTE per 100-patient cycle with Len-dex was 0.3 [95% CI. 0.1-0.4; I2:92%], Len-dex with PI was 0.9 [95% CI. 0.3-1.6; I2: 69%], Len-dex with doxorubicin was1.5 [95% CI. 0.7-2.2; I2: 0%] and MPR was 0.3 [95% CI. 0.2-0.4; I2: 0%]. Notably, the incidence of VTE was higher with Carfilzomib-Len-dex when compared to Bortezomib-Len-dex regimens. Two trials with Len-dex + Doxorubicin had a higher rate of VTE irrespective of the dex dose. The most common modes of thromboprophylaxis used were ASA (range, 70-325 mg) and low molecular weight heparin. Conclusion: Patients with newly diagnosed MM receiving contemporary Len-based regimens have a significant incidence of VTE despite adequate thromboprophylaxis. However, the incidence rate compares favorably with prior estimate. The rate of VTE was highest with the use of Len-dex + Doxorubicin triplet regimen. In the Len-dex+PI subgroup, the incidence of VTE was higher in trials using Carfilzomib-Len-dex compared to Bortezomib-Len-dex regimen. These findings can be clinically applied at an individual level to choose a Len-based combination regimen based on the risk of thrombosis. New prophylactic agents like direct oral anticoagulants should be tested to further decrease the rate of VTE with Len-based combination regimens. Disclosures Khorana: Janssen: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy; Bayer: Consultancy. Majhail:Anthem, Inc.: Consultancy; Incyte: Honoraria; Atara: Honoraria.

Maternal and Neonatal Effect of Fentanyl as a Premedication before Induction of General Anesthesia in Cesarean Surgery: A Systematic Review and Meta-analysis of Randomized Clinical Trials

2019 ◽  
Vol 15 (4) ◽  
pp. 232-237
Author(s):  
Mir Hadi Musavi ◽  
Behzad Jodeiri ◽  
Keyvan Mirnia ◽  
Morteza Ghojazadeh ◽  
Zeinab Nikniaz
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Cesarean Section ◽  
General Anesthesia ◽  
Apgar Score ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Intravenous Fentanyl ◽  
Neonatal Effect ◽  
Fentanyl Group

Background: Although, some clinical trials investigated the maternal and neonatal effect of fentanyl as a premedication before induction of general anesthesia in cesarean section, to the best of our knowledge, there is no systematic review to summarize these results. Objectives: The present systematic review and meta-analysis evaluated the maternal and neonatal effect of intravenous fentanyl as a premedication before induction of general anesthesia in cesarean section. Methods: The databases of Pubmed, Embase, Scopus and Cochrane library were searched till July 2017 to identify randomized clinical trials which evaluated the effects of intravenous fentanyl as a premedication before induction of general anesthesia compared with placebo on neonate first and fifth minute Apgar score and maternal heart rate and mean arterial pressure (MAP) in cesarean section. Standard Mean difference (SMD) was calculated and I-square statistic test was used for heterogeneity analysis. Results: The present systematic review and meta-analysis consisted of three clinical trials including 180 women in labor. Considering the results of meta-analysis, there is no significant differences between fentanyl and placebo in the case of Apgar score at 1 minute; however, the Apgar score of 5 minutes was significantly lower in fentanyl group compared with placebo (SMD -0.68, 95%CI: - 0.98, -0.38, p<0.001). In the term of maternal hemodynamics, the heart rate (SMD -0.43, 95%CI: - 0.72, -0.13, p=0.004) and MAP (SMD -0.78, 95% CI: -1.09, -0.48, p<0.001) in fentanyl group were significantly lower compared with placebo group. Conclusion: The present meta-analysis showed that using intravenous fentanyl as a premedication before induction of general anesthesia had adverse effects on neonate Apgar score. However, it had positive effects on preventing adverse consequences of intubation on maternal hemodynamics.

scholarly journals Effect of photobiomodulation in secondary intention gingival wound healing—a systematic review and meta-analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Pooya Ebrahimi ◽  
Mahdi Hadilou ◽  
Ferdos Naserneysari ◽  
Amirmohammad Dolatabadi ◽  
Rana Tarzemany ◽  
...  
Keyword(s):  
Systematic Review ◽  
Wound Healing ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Healing Process ◽  
Adjunctive Treatment ◽  
Control Groups ◽  
Secondary Intention ◽  
Post Operative Pain

Abstract Background Photobiomodulation is widely being used to improve the wound healing process in dentistry and a vast majority of studies have proven its benefits. But there are plenty of knowledge gaps according to the optimal laser characteristics which should be used to maximize the healing effects of lasers. The goal of this systematic review and meta-analysis was to determine the effect of photobiomodulation (PBM) as an adjunctive treatment to periodontal therapies to evaluate secondary intention gingival wound healing and post-operative pain. Methods Five databases (PubMed, Embase, Scopus, ProQuest, and Web of Sciences) were searched up to November 30, 2020, for clinical trials that reported the result of the application of PBM on secondary gingival healing wounds and post-operative pain and discomfort after periodontal surgeries. Two independent reviewers selected the eligible studies and the outcomes of interest were extracted. The quality of eligible studies was assessed using the Cochrane Handbook for Systematic Reviews of Interventions. Results Ultimately, twelve studies were included in this review. The application of PBM as an adjunct to periodontal surgeries resulted in a significant improvement in wound healing indices. The Landry wound healing index at the 7th post-operative day was significantly improved (SMD = 1.044 [95% CI 0.62–1.46]; p < 0.01) in PBM + surgery groups compared to the control groups. There was also a statistically significant increase in the complete wound epithelialization (RR = 3.23 [95% CI 1.66–6.31]; p < 0.01) at the 14th post-operative day compared to the control groups. The methods used to assess the post-operative pain were heterogeneous, and therefore the results were limited which made the meta-analysis for post-operative pain assessment not possible. Conclusion Based on the results of this review, PBM can be effectively used as a method to improve secondary intention wound healing. High-quality randomized clinical trials, however, are needed in the future to identify the optimal PBM irradiation parameters and the effect of PBM on post-operative pain.

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