Comparison of acalabrutinib plus obinutuzumab, ibrutinib plus obinutuzumab and venetoclax plus obinutuzumab for untreated CLL: a network meta-analysis

Abstract

The optimal chemotherapy-free regimens for treatment-naive CLL still remains undefined. We searched relevant published reports. Three trials with 1017 subjects were identified. In the network meta-analysis, acalabrutinib plus obinutuzumab (Aca + Obi) improved PFS than ibrutinib plus obinutuzumab (Ibu + Obi) (HR:0.43, p = .02) and venetoclax plus obinutuzumab (Ven + Obi) (HR:0.30, p < .001) as IRC assessment. Sensitivity analysis of investigator assessment also showed improved PFS with Aca + Obi than Ibu + Obi (HR:0.46, p = .04) and Ven + Obi (HR:0.34, p = .002). Among these first-line treatments (Aca + Obi, Ibu + Obi, Ven + Obi and chlorambucil plus obinutuzumab (Chl + Obi)), Aca + Obi regimen had the highest probability of 99.1% (IRC assessment) or 98.0% (investigator assessment) to reach the longest PFS. The survival advantage with Aca + Obi was not statistically significant, compared to Ibu + Obi (HR:0.51, p = .21) and Ven + Obi (HR:0.38, p = .07). No significant difference was found in AEs analysis. Our data indicated that Aca + Obi seemed to prolong the PFS than Ibu + Obi and Ven + Obi. Considering our limits, prospective clinical trials directly comparing these regimens are warranted.

Keywords:

• Acalabrutinib
• obinutuzumab
• ibrutinib
• venetoclax
• chronic lymphocytic leukemia
• meta-analysis

Authors’ contributions

Zhixin Sheng participated in the design of the study and performed the statistical analysis. Shilei Song and Miao Yu extracted the data from those trials. Hongguang Zhu, Anran Gao, Weijie Gao and Xuehong Ran helped to perform the statistical analysis. Da Huo helped to perform the statistical analysis and drafted the manuscript. All authors read and approved the final manuscript.

Ethical approval

This pooled analysis was approved by the institutional review boards of Weifang People’s Hospital, in accordance with the Helsinki Declaration.

Acknowledgements

We are indebted to Feng Wang for assistance with data analysis and critiquing the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Availability of data and materials

This analysis is a meta-analysis which overview and extracted data from previous published papers. These enrolled trials were shown in Table 1. All these papers can be found on-line.

Additional information

Funding

The work described in this paper was supported by the grants from the Science and Technology Development Program of Weifang [No. 2018YX049 and No. 2018YX004].