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Background:Background: Zanubrutinib is an oral, highly selective, next-generation Bruton tyrosine kinase inhibitor. Efficacy of zanubrutinib was compared with bendamustine + rituximab (BR) in adult patients with treatment-naïve (TN) chronic lymphocytic leukemia (CLL) in the phase 3 SEQUOIA trial (NCT03336333). However, efficacy of zanubrutinib compared with other frontline CLL treatments remains unknown. Aims:Aims: The goal of this network meta-analysis of randomized controlled trials (RCTs) was to estimate the relative efficacy of zanubrutinib compared with standard frontline treatments for CLL. Methods:Methods: A total of 4 relevant RCTs were identified by a targeted literature review conducted throughout January 2022, CLL11 (NCT01010061), ALLIANCE (NCT01886872), MABLE (NCT01056510), and SEQUOIA. A feasibility assessment was performed to ensure that RCTs included within each population strata did not differ with respect to effect modifiers including presence of mutation, age, del11, and del17 status. A network was constructed for the composed 4 RCTs to compare the efficacy of zanubrutinib with bendamustine + rituximab, chlorambucil + obinutuzumab, chlorambucil + rituximab, and ibrutinib in patients with previously untreated CLL. Bayesian NMA models were conducted to simultaneously synthesize hazard ratio (HR) and 95% credible intervals (CI) for investigator-assessed progression-free survival (PFS). A constant hazard ratio was assumed in the NMA analysis. Statistical analyses were performed using codes suggested by the National Institute for Health and Care Excellence. Results: Results: The efficacy results of the NMA indicated a statistically significant improvement in PFS for zanubrutinib over bendamustine + rituximab (HR = 0.42; [95% CI = 0.27, 0.65]), chlorambucil + obinutuzumab (0.45 [0.23, 0.86]), and chlorambucil + rituximab (0.22 [0.12, 0.41]). Zanubrutinib achieved comparable PFS to ibrutinib (1.07 [0.59, 1.94]).

Purpose: Evidence from observational researches and clinical trials showed the relationship between gut microbiomes (GMs) and hematological malignancies. Nevertheless, the causal role of GM taxa in development of hematological malignancies remains to be explored. Therefore, we aim to assess the causal links between 196 GM taxa and seven common hematological malignancies using the two-sample Mendelian randomization (MR) analyses. Methods: All datasets were derived from published genome-wide association studies (GWAS) statistics. The primary analysis was performed using random effects inverse variance weighted (IVW). To verify the robustness of the MR results, we performed several sensitivity analyses such as Egger intercept test, the Cochran Q test, MR pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out analysis. Results: We revealed the family Oxalobacteraceae would increase the risk of myeloid leukemia by the Bonferroni correction [odds ratio (OR): 2.08, 95% CI: 1.49, 2.90, p = 1.68E-05]. In addition, 22 nominally significant associations between genetic liability in GMs and hematological malignancies were also found (P < 0.05). Sensitivity analysis verified the robustness of the above causal relationships. Conclusion: This study confirms the causal relationship between GMs and hematological malignancies and may provide new insights to the mechanistic and clinical researches of GM-mediated hematological malignancies.

Purpose: Evidence from observational researches and clinical trials showed the relationship between gut microbiomes (GMs) and hematological malignancies. Nevertheless, the causal role of GM taxa in development of hematological malignancies remains to be explored. Therefore, we aim to assess the causal links between 196 GM taxa and seven common hematological malignancies using the two-sample Mendelian randomization (MR) analyses. Methods: All datasets were derived from published genome-wide association studies (GWAS) statistics. The primary analysis was performed using random effects inverse variance weighted (IVW). To verify the robustness of the MR results, we performed several sensitivity analyses such as Egger intercept test, the Cochran Q test, MR pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out analysis. Results: We revealed the family Oxalobacteraceae would increase the risk of myeloid leukemia by the Bonferroni correction [odds ratio (OR): 2.08, 95% CI: 1.49, 2.90, p = 1.68E-05]. In addition, 22 nominally significant associations between genetic liability in GMs and hematological malignancies were also found (P < 0.05). Sensitivity analysis verified the robustness of the above causal relationships. Conclusion: This study confirms the causal relationship between GMs and hematological malignancies and may provide new insights to the mechanistic and clinical researches of GM-mediated hematological malignancies.