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PloS One 2022Currently, there are no approved options to prevent or treat chemotherapy-induced thrombocytopenia (CIT). We performed a systematic literature review and meta-analysis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Currently, there are no approved options to prevent or treat chemotherapy-induced thrombocytopenia (CIT). We performed a systematic literature review and meta-analysis on use of thrombopoietic agents for CIT.
PATIENTS AND METHODS
We searched Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PubMed, EMBASE, ClinicalTrials.gov, and health technology assessments from January 1995 to March 2021 for studies evaluating thrombopoietic agents for CIT, including recombinant human thrombopoietin (rhTPO), megakaryocyte growth and development factor (MGDF), romiplostim, and eltrombopag. Random effects meta-analyses were conducted for efficacy and safety endpoints.
RESULTS
We screened 1503 titles/abstracts, assessed 138 articles, and abstracted data from 39 publications (14 recombinant human thrombopoietin, 7 megakaryocyte growth and development factor, 9 romiplostim, 8 eltrombopag, and 1 romiplostim/eltrombopag). Random effects meta-analyses of data from multiple studies comparing thrombopoietic agents versus control (comparator, placebo, or no treatment) showed that thrombopoietic agents did not significantly improve chemotherapy dose delays and/or reductions (21.1% vs 40.4%, P = 0.364), grade 3/4 thrombocytopenia (39.3% vs 34.8%; P = 0.789), platelet transfusions (16.7% vs 31.7%, P = 0.111), grade ≥ 2 bleeding (6.7% vs 16.5%; P = 0.250), or thrombosis (7.6% vs 12.5%; P = 0.131). However, among individual studies comparing thrombopoietic agents with placebo or no treatment, thrombopoietic agents positively improved outcomes in some studies, including significantly increasing mean peak platelet counts (186 x 109/L with rhTPO vs 122 x 109/L with no treatment; P < 0.05) in one study and significantly increasing platelet count at nadir (56 x 109/L with rhTPO vs 28 x 109/L with not treatment; P < 0.05) in another study. Safety findings included thrombosis (n = 23 studies) and bleeding (n = 11), with no evidence of increased thrombosis risk with thrombopoietic agents.
CONCLUSION
Our analyses generate the hypothesis that thrombopoietic agents may benefit patients with CIT. Further studies with well-characterized bleeding and platelet thresholds are warranted to explore the possible benefits of thrombopoietic agents for CIT.
Topics: Anemia; Antineoplastic Agents; Hemorrhage; Humans; Receptors, Fc; Recombinant Fusion Proteins; Recombinant Proteins; Thrombocytopenia; Thrombopoiesis; Thrombopoietin
PubMed: 35679540
DOI: 10.1371/journal.pone.0257673 -
British Journal of Haematology Dec 2014Thrombocytopenia is common (40-65%) and potentially serious in myelodysplastic syndromes (MDS). A systematic review was conducted to determine the safety and efficacy of... (Meta-Analysis)
Meta-Analysis Review
Thrombocytopenia is common (40-65%) and potentially serious in myelodysplastic syndromes (MDS). A systematic review was conducted to determine the safety and efficacy of adding a thrombopoietin-receptor (THPO-R) agonist to standard MDS treatment. MEDLINE, EMBASE and CENTRAL databases were searched. We included randomized controlled trials comparing a THPO-R agonist to placebo. A meta-analysis of the effects was performed. Endpoints included bleeding and platelet transfusion rates, risk of progression to acute myeloid leukaemia (AML) and mortality. Three hundred and eighty four patients from five trials were included, four using romiplostim and one using eltrombopag. Overall, the relative risk (RR) of bleeding with romiplostim versus placebo was 0·84 [95% confidence interval (CI): 0·57-1·24]. However, compared to placebo, romiplostim significantly decreased the exposure-adjusted bleeding rate (RR 0·92; 95% CI: 0·86-0·99), as well as the exposure-adjusted platelet transfusion rate (RR 0·69; 95% CI: 0·53-0·88). The RR of AML progression with romiplostim was 1·36 (95% CI: 0·54-3·40), however the outcome data were judged as higher risk of bias. Romiplostim is promising in its ability to decrease patient-important outcomes: bleeding and platelet transfusion need. Although the risk of AML progression was not increased, due to unclear risk of bias in the data, this safety concern is difficult to assess. Therefore, romiplostim cannot yet be routinely recommended. Early eltrombopag data is promising.
Topics: Female; Hemorrhage; Humans; Leukemia, Myeloid, Acute; MEDLINE; Male; Myelodysplastic Syndromes; Platelet Transfusion; Randomized Controlled Trials as Topic; Receptors, Fc; Receptors, Thrombopoietin; Recombinant Fusion Proteins; Risk Factors; Thrombopoietin
PubMed: 25155450
DOI: 10.1111/bjh.13088 -
Frontiers in Pharmacology 2021Thrombopoietin receptor agonists (TPO-RAs) play a crucial role in stimulating thrombopoiesis. However, conventional meta-analyses have shown inconsistent results...
Comparative Efficacy and Safety of Thrombopoietin Receptor Agonists in Adults With Thrombocytopenia: A Systematic Review and Network Meta-analysis of Randomized Controlled Trial.
Thrombopoietin receptor agonists (TPO-RAs) play a crucial role in stimulating thrombopoiesis. However, conventional meta-analyses have shown inconsistent results regarding the efficacy of thrombopoietin receptor agonists versus placebo. Therefore, we performed a network meta-analysis to assess the effects of five TPO-RAs indirect comparison. For this network meta-analysis, we considered randomized trials that included any of the following interventions: avatrombopag, lusutrombopag, eltrombopag, romiplostim, recombinant human thrombopoietin (rhTPO). We searched the , , , , and databases for randomized controlled clinical trials from inception to January 31, 2021. We use randomized controlled clinical trials of TPO-RAs for treatment of immune thrombocytopenia in adults. The primary outcome was the number of patients achieving platelet response which was defined as the achievement of a platelet count of more than 30 or 50 cells × 10/L in the absence of rescue therapy, and the secondary outcome was the therapy-related serious adverse events and incidence of bleeding episodes. To obtain the estimates of efficacy and safety outcomes, we performed a random-effects network meta-analysis. These estimates were presented as odds ratios with 95% confidence intervals. We use surface under the cumulative ranking probabilities to rank the comparative effects and safety of all drugs against the placebo. In total, 2,207 patients were analyzed in 20 clinical trials. All preparations improved the point estimates of platelet response when compared with the placebo. Avatrombopag and lusutrombopag had the best platelet response compared to the placebo, the former had a non-significant advantage compared to the latter [odds ratio (OR) = 1.91 (95% confidence interval: 0.52, 7.05)]. The treatments were better than eltrombopag, romiplostim, rituximab, and rhTPO + rituximab, with corresponding ORs of 3.10 (1.01, 9.51), 9.96 (2.29, 43.29), 33.09 (8.76, 125.02), and 21.31 (3.78, 119.98) for avatrombopag and 1.62 (0.63, 4.17), 5.21 (1.54, 17.62), 17.34 (5.15, 58.36), and 11.16 (2.16, 57.62) for lusutrombopag. Regarding bleeding, the placebo group had the highest probability of bleeding, whereas lusutrombopag had the lowest risk of bleeding when compared to the placebo. Adverse events were slightly higher in patients receiving rituximab than in those receiving placebo or other treatments. Overall, this meta-analysis showed that avatrombopag may yield the highest efficacy because it has the most favorable balance of benefits and acceptability.
PubMed: 34393785
DOI: 10.3389/fphar.2021.704093