Venetoclax alone or in combination with other regimens treatment achieve deep and sustained remission of relapsed/refractory chronic lymphocytic leukemia: a meta-analysis

Recently, the use of novel targeted drugs significantly improved the overall response rate (ORR) and survival of patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL). The treatment of R/R CLL has been gradually developed from traditional chemotherapy to targeted therapy. Venetoclax has been proved to be effective for R/R CLL as a single agent or in combination with various regimens. However, the data from clinical studies were still limited, especially since a large number of studies were single arms. Considering that there were few kinds of research in this regard and the data were not uniform, a meta-analysis was conducted to describe ORR and undetectable minimal residual disease (uMRD) of venetoclax in patients with R/R CLL. The pooled cumulative prevalence of total ORR was 82% (95% CI 77-87%), and the pooled ORR in venetoclax + anti-CD20 antibody-based group was 89% (95% CI 83-94%). There were significant differences among venetoclax monotherapy group, venetoclax + ibrutinib group and venetoclax + anti-CD20 group with pooled uMRD of 39% (95% CI 31-47%), 57% (95% CI 50-64%) and 43% (95% CI 19-70%), respectively (P = 0.004 < 0.05). Pooled ORR of patients with high-risk cytogenetic in venetoclax monotherapy group was 73% (95% CI 61-83%). No significant difference was observed in comparison with patients without high-risk cytogenetic who received the same treatment (P = 0.518). Our research results indicate that venetoclax combined with anti-CD20 monoclonal antibody may be an effective treatment for patients with R/R CLL, especially for CLL patients with high-risk cytogenetic factors. Furthermore, ibrutinib in combination with venetoclax showed a longer remission time, the deeper remission degree and uMRD-negative rate gradually increased with the extension of the treatment time.