scholarly journals Reduced-Intensity Versus Myeloablative Conditioning for Allogeneic Hematopoietic Cell Transplantation in Patients with Myelodysplastic Syndrome: A Systematic Review and Meta-Analysis of Randomized Clinical Trials & Cohort Studies

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-26
Author(s):  
Arshia Akbar ◽  
Zunairah Shah ◽  
Muhammad Ali Aziz ◽  
Muhammad Yasir Anwar ◽  
Saman Bahram ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Myelodysplastic Syndrome ◽  
Cohort Studies ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Chronic Gvhd ◽  
P Value ◽  
Grade 3 ◽  
Risk Of Relapse

Background: Conditioning regimen given before allogeneic hematopoietic stem cell transplantation (allo-HSCT) contributes significantly to the outcomes following transplant for myelodysplastic syndrome (MDS). Myeloablative conditioning (MAC) regimens are often associated with a lower risk of relapse; however, their use is often limited by toxicity and a higher risk of non-relapse mortality (NRM). Reduced-intensity conditioning (RIC) regimens are associated with a higher risk of relapse, a lower NRM, a lower incidence of graft versus host disease (GVHD), and hence is feasible in patients with advanced age or comorbidities. This study highlights the importance of the difference between the two interventions used in allo-HSCT for myelodysplastic syndrome (MDS). Methods: We conducted a comprehensive literature search using PubMed, Clinicaltrial.gov, Embase, Cochrane, and Web of Science on 5th May 2020 with no restriction of language or period. Initial research revealed 1698 articles. After excluding review articles, duplicates, and non-relevant articles, we included two randomized clinical trials and three cohort studies, which reported overall survival (OS), relapse-free survival (RFS), relapse incidence (RI), and incidence of acute and chronic (GVHD). Based on inclusion criteria, two randomized clinical trials (BMT CTN 0901 Trial Scott et al. 2017 & EBMT RICMAC Trial Kroger et al. 2017) and three cohort studies (BBMT 55226 Park et al. 2018, BBMT Orozco et al. 2019, BMT Alatrash et al. 2019) were included. Results: Among combined MDS and acute myeloid leukemia (AML) patients (n=1188) enrolled in 5 studies, 651 patients had MDS. Patients underwent MAC (n=484) or RIC (n=692) followed by either a matched related donor (MRD), n=236, or matched unrelated donor (MUD), n=236, allo-HCT. The median age range at the time of transplant was 50-54 years The use of RIC causes statistically non-significant trend of improved overall survival (OS) (OR 1.11: 95% CI: 0.74-1.67, p-value= 0.61) along with more risk of relapse incidence (RI) (R 1.34: 95% CI: 0.56-3.18, p value= 0.51), and reduced relapse free survival (RFS) (OR 0.88, 95% CI: 0.55-1.44: p value= 0.59). Differences were found in terms of safety of both conditioning regimens. MAC allo-HCT have more acute GVHD, grade 3 and 4 (OR 0.66: 95% CI: 0.29-1.52, p value= 0.33) and chronic GVHD, grade 3 and 4 (OR 0.72: 95% CI: 0.41-1.27: p value= 0.26) and treatment-related mortality (TRM) (OR 0.83, 95% CI: 0.37-1.86, p value= 0.65). The meta-analysis results are shown in figure-1. Conclusion: In adult MDS patients undergoing allo-HSCT, RIC is associated with improved overall survival, but at the cost of reduced RFS, and a higher risk of relapse. MAC, on the other hand, is associated with more treatment-related mortality and GVHD. Results of our analysis point out these trends but these are not statistically significant Figure 1 Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

scholarly journals The Value of PD-L1 Expression as Predictive Biomarker in Metastatic Renal Cell Carcinoma Patients: A Meta-Analysis of Randomized Clinical Trials

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1945 ◽  
Author(s):  
Alberto Carretero-González ◽  
David Lora ◽  
Isabel Martín Sobrino ◽  
Irene Sáez Sanz ◽  
María T. Bourlon ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Clinical Trials ◽  
Renal Cell ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Standard Of Care ◽  
Predictive Biomarker ◽  
P Value ◽  
Metastatic Rcc

Immune checkpoint inhibitors (ICIs) are soluble antibodies that have dramatically changed the outcomes including overall survival in a subset of kidney tumors, specifically in renal cell carcinoma (RCC). To date, there is no a single predictive biomarker approved to be used to select the patients that achieve benefit from ICIs targeting. It seems reasonable to analyze whether the programmed death-ligand 1 (PD-L1) expression could be useful. To assess the role of PD-L1 expression as a potential predictive biomarker for benefit of ICIs in RCC patients, we performed a search of randomized clinical trials (RCTs) comparing ICIs (monotherapy or in combination with other therapies) to standard of care in metastatic RCC patients according to PRISMA guidelines. Trials must have included subgroup analyses evaluating the selected outcomes (progression-free survival (PFS) and overall survival (OS)) in different subsets of patients according to PD-L1 expression on tumor samples. Hazard ratios with confidence intervals were used as the measure of efficacy between groups. A total of 4635 patients (six studies) were included (ICIs arm: 2367 patients; standard of care arm: 2268 patients). Globally, PFS and OS results favored ICIs. Differential expression of PD-L1 on tumor samples could select a subset of patients who could benefit more in terms of PFS (those with higher levels; p-value for difference between subgroups: <0.0001) but it did not seem to impact in OS results (p-value for difference: 0.63). As different methods to assess PD-L1 positivity were used among trials, this heterogeneity could have an influence on the results. PD-L1 could represent a biomarker to test PFS in clinical trials but its value for OS is less clear. In this meta-analysis, the usefulness of PD-L1 expression as a predictive biomarker to select treatment in metastatic RCC patients was not clearly shown.

High Dose Chemotherapy and Autologous Stem Cell Transplantation in the Primary Therapy of Advanced Follicular Lymphoma in Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2314-2314
Author(s):  
Murtadha K. Al-Khabori ◽  
John de Almeida ◽  
Gordon Guyatt ◽  
John Kuruvilla ◽  
Michael Crump
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
P Value ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
American Society

Abstract Abstract 2314 Poster Board II-291 Background: The impact of high dose therapy and autologous stem cell transplantation (ASCT) in the upfront management of adults with advanced follicular lymphoma (FL) on overall survival remains uncertain. A number of randomized clinical trials (RCTs) compared ASCT to conventional dose chemotherapy regimens. We performed a systematic review to address this question. Objective: To compare the overall survival (OS), event free survival (EFS), treatment related mortality (TRM), incidence of secondary myelodysplasia/acute myeloid leukemia (t-MDS/AML) and secondary solid tumors within the ASCT strategy and chemotherapy. Methods: We performed a search of MEDLINE, EMBASE, CENTRAL, American Society of Hematology (ASH), American Society of Clinical Oncology (ASCO), BIOSIS, PAPERSFIRST, PROCEEDINGS, clinical trials registries (National Cancer Institute, clinicaltrials.gov) and bibliographies of relevant studies for randomized controlled trials comparing myelo-ablative chemotherapy with ASCT to any chemotherapy in adults with untreated advanced (Ann Arbor stage III-IV) FL. Two reviewers recorded study characteristics, methodology and outcomes. Disagreement was resolved by discussion. Results: Seven trials were identified and included in the systematic review but only four with available data reporting 941 patients were included in the meta-analysis. Three trials excluded: one was never reported; the second was stopped early due to the increased toxicities in the transplant arm; and the third showed no significant difference in EFS or OS at an interim analysis with insufficient data for the meta-analysis. None of these studies has been published. In one of the 7 trials patients in both arms received rituximab during the induction treatment. High dose therapy and ASCT did not result in improved OS compared to standard therapy, Hazard Ratio (HR) 1.15 (0.85, 1.55). The HR for EFS was 0.61 (0.34, 1.11) with substantial heterogeneity, I2 =91%, Chi2 p value <0.00001. Only the duration of the follow up could explain this heterogeneity with statistically significant subgroup interaction, P <0.00001. The incidence of t-MDS/AML ranged from 1% to 7% in the ASCT arms of the four studies, with a difference in favour of standard chemotherapy, Risk Difference (RD) 4% (95%CI: -1%, 8%), and significant heterogeneity (Chi2 p value of 0.008, I2=75%) due to difference in duration of follow up (p=0.005 for the subgroup differences).There was no increase in mortality directly attributable to treatment (RD 0%, 95%CI: -2%, 1%) nor in secondary solid tumors (RD 1%, 95%CI: -2%, 4%). Conclusions: High dose therapy and ASCT as part of initial does not improve overall survival despite a trend towards better disease control, likely because of the effectiveness of second and subsequent lines of treatment for FL. T-MDS/AML occurs more commonly following ASCT and represents a significant risk to patients. With one exception, these studies were conducted before the introduction of monoclonal B cell antibodies. Future trials of ASCT in the context of current chemo-immunotherapy approaches to FL would further inform this issue. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Safety and Efficacy of Four Drug Versus Three Drug Regimens Among Patients with Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 3-3
Author(s):  
Saad Ullah Malik ◽  
Nazma Hanif ◽  
Priyanka Kumari ◽  
Khadija Noor Sami ◽  
Chase Warner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Standard Of Care ◽  
Drug Regimen ◽  
P Value ◽  
Newly Diagnosed ◽  
Drug Regimens ◽  
Grade 3

Introduction: During recent years there has been a boom in the availability of treatments for multiple myeloma (MM). Based on the status of disease (newly diagnosed or relapsed/refractory), several regimens have successfully improved progression free survival (PFS) and overall survival (OS) in these two types of patients. Triple drug regimen is considered the current standard of care for newly diagnosed MM patients. However, with the advent of four drug regimens, some studies demonstrated a significant improvement in PFS and OS compared to standard of care where as others showed marginal to no difference. Also, it remains unclear whether the benefits of using four drug regimen outweigh the risks. Thus, the aim of our meta-analysis was to compare the efficacy and safety of four drug versus three drug regimens among newly diagnosed multiple myeloma patients. Methods: We built a PICO based search strategy using keywords like "multiple myeloma", "randomized clinical trials" and ran literature search on PubMed, Embase, Wiley Cochrane Library, Web of Science and ClinicalTrials.gov ranging from the date of inception till 16th July, 2020. A pre-validated data extraction sheet was used to extract data on PFS, OS and ≥Grade 3 hematologic adverse events at the longest follow-up. We included only randomized clinical trials (RCTs) comparing four versus three drug regimen in newly diagnosed MM patients. We excluded studies other than RCTs, studies conducted on relapsed refractory MM patients or other plasma cell dyscrasias. A generic variance weighted random effects model (DerSimonian and Laird) was used to derive hazard ratio estimates along with their 95% confidence intervals (CIs) for PFS and OS. Risk ratio along with its 95% CIs was estimated for Grade ≥3 hematologic adverse events. Heterogeneity was assessed with Cochrane Q -statistic and was quantified with I2 test (I2 &gt;50% was consistent with a high degree of heterogeneity). A pre-specified sensitivity analysis was also performed for risk of adverse events. Cochrane Collaboration's tool was used to assess the quality of included RCTs and GRADE was used to rate the quality of evidence. Results: Initial search retrieved 7622 titles. After duplicate removal, 4880 articles were left. Following initial screening, 58 articles were considered for full text review. Of these only 3 studies (n=2277) met inclusion criteria. Four drug regimens included daratumumab, bortezomib, melphalan-prednisone (D-VMP), daratumumab, bortezomib, thalidomide-dexamethasone (D-VTd) and bortezomib and melphalan prednisone and thalidomide (VMPT-VT) respectively. Whereas, three drug regimens were bortezomib, melphalan-prednisone (VMP), bortezomib, thalidomide-dexamethasone (VTd) and bortezomib, melphalan and prednisone (VMP) respectively. There was a significant improvement in PFS when 4 vs 3 drug regimens were compared in patients with newly diagnosed MM (HR: 0.53, 95% CI: 0.46-0.62, p-value:&lt;0.001, I2: 0%). Also, OS improved significantly in four drug regimen group (HR: 0.62, 95% CI: 0.51-0.76, p-value:&lt;0.001, I2: 3.5%). There was no statistically significant difference in any grade ≥3 hematologic adverse events when 4 vs 3 drug regimens were compared (RR: 1.26, 95% CI: 0.93-1.73, p-value:0.14, I2: 93%). Sensitivity analysis after removing D-VTd regimen from any grade ≥3 hematologic adverse events revealed similar results (RR: 1.05, 95% CI: 0.97-1.13, p-value:0.23, I2: 23%) confirming the robustness of analysis. When each hematologic adverse event was looked at separately, there was no difference between 4 vs 3 drug regimen in rates of anemia (RR: 0.99, 95% CI: 0.76-1.28, p-value:0.92, I2: 0%), neutropenia (RR: 1.39, 95% CI: 1.00-1.94, p-value:0.05, I2: 85%) and thrombocytopenia (RR: 1.13, 95% CI: 0.92-1.39, p-value:0.24, I2: 33%). There was low risk of bias and strength of evidence was of moderate. Conclusion: Using four drug regimens, compared to three drug regimens, significantly improves PFS and OS among newly diagnosed multiple myeloma patients without any difference in the risk of ≥3 grade hematologic adverse events. Further randomized clinical trials are required to establish four drug regimen as standard of care for patients with newly diagnosed multiple myeloma. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

scholarly journals Safety and Efficacy of Tyrosine Kinase Inhibitors in Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 18-18
Author(s):  
Farwah N. Fatima ◽  
Faiz Anwer ◽  
Muhammad Ashar Ali ◽  
Muhammad Yasir Anwar ◽  
Sana Khan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Acute Myeloid Leukemia ◽  
Placebo Group ◽  
Myeloid Leukemia ◽  
Randomized Clinical Trials ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Salvage Chemotherapy ◽  
Grade 3 ◽  
Acute Myeloid

Introduction: Five year overall survival for acute myeloid leukemia (AML) is estimated to be less than 30%. Encouraging results seen with the tyrosine kinase inhibitors (TKIs), midostaurin and gilteritinib resulted in the approval of these molecular targeted therapies for patients with FLT3 Mutated AML. Other TKIs like sorafenib and quizartinib, have ongoing clinical trials. In this systematic review and meta-analysis, we assessed the efficacy and safety of TKIs for the treatment of newly diagnosed (ND) and relapsed refractory (R/R) AML. Methods: A search was performed on PubMed, Cochrane, Embase, and clinicaltrials.gov. We used the keywords "tyrosine kinase inhibitors" AND "acute myeloid leukemia" from the inception of literature till 07/10/2020. We screened 3245 articles and included 5 randomized clinical trials (RCTs) (N=1919) in this meta-analysis. We extracted data for efficacy (i-e, OS, CR, ORR, EFS) and safety (≥grade 3 treatment related adverse events (TRAE). We excluded case reports, case series, preclinical studies, review articles, meta-analysis, observational studies, and controlled clinical studies not providing any information about the efficacy or safety of TKI. We used the R programming language (version 4.0.2) to conduct a meta-analysis. Results: In the 5 RCTs (n=1919), the age range was 18-85 years. 1675 participants had FLT-3 mutation (Table 1). In 2 RCTs (N=738), two TKIs (gilteritinib and quizartinib) (N=492) were compared with salvage chemotherapy (N=246). Risk ratio (RR) of overall response rate (ORR) and complete remission (CR) was 2.43 (95% CI=1.97-3.00, I2=0) and 2.09 (95% CI=1.5-2.90, I2=48%), respectively in favor of TKIs. The hazard ratio (HR) for overall survival (OS) was 0.70 (95% CI=0.58-0.84, I2=0) in favor of TKIs. (Fig 1-3). The median OS was 6.2 months in the quizartinib group vs. 4.7 months in the chemotherapy group. Similarly, median OS was 9.3 months in the gilteritinib group vs. 5.6 months in the chemotherapy group. Grade 3 or higher TRAEs (anemia, infections, sepsis, febrile neutropenia, and liver toxicity) were reported more often in the TKI group vs. salvage chemotherapy group. (Fig 4-6). In 3 RCTs (N=1181), two TKIs (midostaurin and sorafenib) (N=597) were compared with placebo (N=582). In the RCT evaluating role of sorafenib in older patients (&gt;60 years) (N=197), RR of CR was 0.75 (95% CI=0.58-0.96) in favor of placebo. Although more patients died in the sorafenib group than the placebo group (23 vs 10 within 60-day period), TRAEs were similar in the two groups. In the remaining 2 RCTs, sorafenib and midostaurin were compared with placebo in younger patients (&lt;60 years old) (N=982). RR of CR was 1.07 (95% CI=0.96-1.19, I2=0) in favor of TKIs and the hazard ratio for OS was 0.80 (95% CI=0.66-0.96, I2=0) in favor of TKIs (Fig 7,8). Median event-free survival (EFS) was 21 months in the sorafenib group vs. 9 months in the placebo group. Similarly, median EFS was 8.2 months in the midostaurin group vs. 3 months in the placebo group. Grade 3 or higher TRAEs (anemia, liver toxicity, infections, and diarrhea) were more common in the TKI group as compared to the placebo group. (Fig 9,10) Conclusion: Gilteritinib and quizartinib were not only better tolerated but also more effective than salvage chemotherapy in patients with FLT-3 mutated AML. In older patients, sorafenib appeared to have lower efficacy and higher toxicity when compared with placebo. In contrast, for younger patients, sorafenib and midostaurin had better efficacy and lower toxicity than placebo. 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.

Meta-analysis of randomized trials testing the biochemical modulation of fluorouracil by methotrexate in metastatic colorectal cancer. Advanced Colorectal Cancer Meta-Analysis Project.

1994 ◽  
Vol 12 (5) ◽  
pp. 960-969 ◽  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Clinical Trials ◽  
Regression Model ◽  
Randomized Clinical Trials ◽  
Tumor Response ◽  
Advanced Colorectal Cancer ◽  
Response Rate ◽  
Meta Analysis ◽  
Biochemical Modulation

PURPOSE Even though fluorouracil (5FU) remains the standard treatment of advanced colorectal cancer, almost 90% of patients treated with 5FU alone do not achieve an objective response to chemotherapy. Biochemical modulation of 5FU by methotrexate (MTX) is an attempt to increase the sensitivity of tumor cells to 5FU. However, despite the inclusion of several hundreds of patients in randomized clinical trials, no definitive evidence is available on the clinical benefit of 5FU/MTX over 5FU alone. A meta-analysis was performed to assess this benefit objectively and quantitatively for tumor response rate and overall survival. DESIGN The meta-analysis was based on individual data of 1,178 patients included in eight randomized clinical trials comparing 5FU alone with 5FU/MTX. Patient data were provided by all principal investigators. The analyses were performed by an independent secretariat, and then discussed with all collaborators. RESULTS Tumor response rate was 10% for patients allocated to 5FU alone (complete response [CR] rate, 2%; partial response [PR] rate, 8%) compared with 19% for patients allocated to 5FU/MTX (CR rate, 3%; PR rate, 16%). This difference was highly significant, with an overall response odds ratio (OR) of 0.51 (95% confidence interval [CI], 0.37 to 0.70) (P < .0001). Median overall survival times were 9.1 months and 10.7 months in the 5FU-alone and 5FU/MTX groups, respectively. This difference was also statistically significant, with an overall survival OR of 0.87 (95% CI, 0.77 to 0.98) (P = .024). Logistic regression model and Cox regression model showed that performance status and randomized treatment were the only two significant predictors of tumor response and survival. CONCLUSION It is concluded that the modulation of 5FU by MTX doubles the response rate to 5FU, and yields a small improvement in survival.

scholarly journals Efficacy and Safety Profile of Ixazomib Based Regimens in Relapsed/Refractory Multiple Myeloma: A Meta-Analysis of Clinical Trials

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 20-21
Author(s):  
Ahmad Iftikhar ◽  
Muhammad Ashar Ali ◽  
Anum Javaid ◽  
Muhammad Abu Zar ◽  
Atif Sohail ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Safety Profile ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Case Series ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Grade 3

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.

scholarly journals The safety, tolerability and mortality reduction efficacy of remdesivir; based on randomized clinical trials, observational and case studies reported safety outcomes: an updated systematic review and meta-analysis

2021 ◽  
Vol 12 ◽  
pp. 204209862110425
Author(s):  
Chenchula Santenna ◽  
Kota Vidyasagar ◽  
Krishna Chaitanya Amarneni ◽  
Sai Nikhila Ghanta ◽  
Balakrishnan Sadasivam ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Antiviral Drug ◽  
Mortality Reduction ◽  
Serious Adverse Events ◽  
Significant Difference ◽  
Grade 3

Introduction: Remdesivir, an experimental antiviral drug has shown to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), both in vitro and in vivo. The present systematic review and meta-analysis were performed to quantify the safety and tolerability of remdesivir, based on safety outcome findings from randomized controlled trials, observational studies and case reports of remdesivir in coronavirus disease 2019 (COVID-19) patients. Methods: We have performed a systematic search in the PubMed, Google Scholar and Cochrane Library using specific keywords such as ‘COVID-19’ OR ‘SARS CoV-2’ AND ‘Remdesivir’. The study endpoints include total adverse events (AEs), serious adverse events (SAEs), grade 3 and grade 4 AEs, mortality and drug tolerability. Statistical analysis was carried out by using Revman 5.4 software. Results: Total 15 studies were included for systematic review, but only 5 randomized clinical trials (RCTs) ( n = 13,622) were included for meta-analysis. Visual inspection of the forest plots for remdesivir 10-day versus placebo and remdesivir 10-day versus 5-day groups revealed that there is a significant difference in SAEs [10-day remdesivir versus control (odds ratio [OR] = 0.55, 0.40–0.74) p = 0.0001; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 0.56, 0.38–0.84) p = 0.005; I2 = 13%]. In grade 4 AEs, there is a significant difference in 10-day remdesivir versus control (OR = 0.32, 0.19–0.54) p = 0.0001; I2 = 0%, but not in comparison to 5-day remdesivir (OR = 0.95, 0.59–1.54) p = 0.85; I2 = 0%. But there is no significant difference in grade 3 AEs [remdesivir 10 day versus control (OR = 0.81, 0.59–1.11) p = 0.19; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.24, 0.86–1.80) p = 0.25; I2 = 0%], in total AEs [remdesivir 10 day versus control (OR = 1.07, 0.66–1.75) p = 0.77; I2 = 79%; remdesivir 10 day versus 5 day (OR = 1.08, 0.70–1.68) p = 0.73; I2 = 54%)], in mortality [10-day remdesivir versus control (OR = 0.93, 0.80–1.08) p = 0.32; I2 = 0%; 10-day remdesivir versus 5-day remdesivir (OR = 1.39, 0.73–2.62) p = 0.32; I2 = 0%)] and tolerability [remdesivir 10 day versus control (OR = 1.05, 0.51–2.18) p = 0.89; I2 = 65%, 10-day remdesivir versus 5-day remdesivir (OR = 0.86, 0.18–4.01) p = 0.85; I2 = 78%]. Discussion & Conclusion: Ten-day remdesivir was a safe antiviral agent but not tolerable over control in the hospitalized COVID-19 patients with a need of administration cautiousness for grade 3 AEs. There was no added benefit of 10- or 5-day remdesivir in reducing mortality over placebo. To avoid SAEs, we suggest for prior monitoring of liver function tests (LFT), renal function tests (RFT), complete blood count (CBC) and serum electrolytes for those with preexisting hepatic and renal impairments and patients receiving concomitant hepatotoxic or nephrotoxic drugs. Furthermore, a number of RCTs of remdesivir in COVID-19 patients are suggested. Plain Language Summary Ten-day remdesivir is a safe antiviral drug with common adverse events in comparison to placebo. The rate of serious adverse events and grade 3 adverse events were significantly lower in 10-day remdesivir in comparison to placebo/5-day remdesivir. There was no significant difference in the rate of tolerability and mortality reduction in 10-day remdesivir over placebo/5-day remdesivir. There were no new safety signals reported in vulnerable populations, paediatric, pregnant and lactating women.

scholarly journals Effect of Foot Reflexology on Constipation: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Zahra Anjoman Azari ◽  
Mojgan Mirghafourvand ◽  
Ciara Hughes ◽  
Shiva Havizari
Keyword(s):  
Clinical Trials ◽  
Fixed Effects ◽  
Primary Outcome ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Gastrointestinal Disorders ◽  
P Value ◽  
Prevalent Symptom

Context: Constipation is a prevalent symptom of gastrointestinal disorders, which has an annoying impact on health and quality of life. On the other hand, reflexology is a popular type of complementary and alternative medicine in medical practices. Objectives: The present study aimed to assess the effect of foot reflexology on constipation symptoms. Methods: Nine databases were systematically searched to detect relevant Randomized Clinical Trials. The current used the Cochrane Risk of Bias tool to evaluate the methodological quality of the included articles. The primary outcome was the improvement of constipation symptoms. The Standardized Mean Difference (SMD) was measured, and random effects were reported instead of the fixed effects due to the high heterogeneity. Results: Out of the 693 articles retrieved from the databases and eight additional records identified through other sources, 496 titles, 48 abstracts, and 16 full-texts were reviewed, and 11 articles were included in this study, out of which nine articles entered the meta-analysis. The findings of the meta-analysis indicated that foot reflexology had a significant effect on the constipation score (SMD: -0.82; 95% CI: -1.47 to -0.17; P value = 0.0001; I2 = 93%) Conclusions: Foot reflexology can effectively improve constipation symptoms; however, clinical trials with better designs are recommended.

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