Evaluation of Bruton tyrosine kinase inhibitors monotherapy and combination therapy in lymphocytic leukemia

BTKi is an effective treatment in chronic lymphocytic leukemia. However, head-to-head clinical trials between BTKi are rare. To explore evidence-based treatment decisions, we conducted this network meta-analysis. We searched in PubMed, Cochrane Library and Embase and selected articles of BTKi treatment in CLL patients, with English restrictions. Objective response rate (ORR), progression-free survival (PFS) and safety were outcomes. Combination therapy and acalabrutinib monotherapy achieved great ORR (greater than 80%). Combination therapy (AO and IR) also performed terrific PFS (> 80%). Compared with ibrutinib monotherapy, zanubrutinib, acalabrutinib and IR showed no significance in overall survival. Diarrhea, hypertension, cardiac events, neutropenia were common adverse events of BTKi therapy. IR had higher incidence of hypertension (0.38, 95% CI 0.28-0.48), and IU was more likely occurred cardiac events. Zanubrutinib monotherapy had lower incidence of total serious adverse reaction (0.42, 95% confidence interval (95% CI): 0.36-0.47),while ibrutinib monotherapy occurred higher adverse reactions of grade ≥ 3 (0.77, 95% CI 0.72-0.82). Although both BTKi monotherapy and combination therapy showed great efficacy, combination therapy did not display priority. Meanwhile, safety of BTKi combination therapy needs to be fully and comprehensively considered.Registration number: CRD42022378732.