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. 2023 Aug;41(4):606-616.
doi: 10.1007/s10637-023-01376-1. Epub 2023 Jul 8.

Indirect comparisons of efficacy of zanubrutinib versus orelabrutinib in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma or relapsed or refractory mantle cell lymphoma

Yuqin Song  1 , Keshu Zhou  2 , Shenmiao Yang  3 , Jianda Hu  4 , Dehui Zou  5 , Sujun Gao  6 , Ling Pan  7 , Tingyu Wang  5 , Haiyan Yang  8 , Huilai Zhang  9 , Daobin Zhou  10 , Jie Ji  7 , Wei Xu  11 , Ru Feng  12 , Jie Jin  13 , Fangfang Lv  14 , Haiwen Huang  15 , Xiaosi Fan  16 , Sheng Xu  16 , Jun Zhu  17
Affiliations

Indirect comparisons of efficacy of zanubrutinib versus orelabrutinib in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma or relapsed or refractory mantle cell lymphoma

Yuqin Song et al. Invest New Drugs. 2023 Aug.

Abstract

We conducted two indirect comparisons to estimate the efficacy of zanubrutinib versus orelabrutinib in Chinese patients with relapsed or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) or R/R mantle cell lymphoma (MCL). An unanchored matching-adjusted indirect comparison (MAIC) was performed in R/R CLL/SLL patients. Individual patient data from zanubrutinib trial (BGB-3111-205) were adjusted to match the aggregated data from the orelabrutinib trial (ICP-CL-00103). A naïve comparison was performed in R/R MCL for the different response assessment methodology and efficacy analysis set between the zanubrutinib (BGB-3111-206) and orelabrutinib (ICP-CL-00102) trials. Efficacy outcomes included ORR and PFS. In R/R CLL/SLL patients, after matching, IRC-assessed ORR was comparable (86.6% vs. 92.5%; risk difference, -5.9% [95% CI: -15.8%-3.8%]); IRC-assessed PFS was similar with a favorable trend in zanubrutinib over orelabrutinib (HR, 0.74 [95% CI: 0.37-1.47]) and the 18-month PFS rate was numerically higher in zanubrutinib (82.9% vs. 78.7%). In R/R MCL patients, naïve comparison showed investigator-assessed ORR was similar (83.7% vs. 87.9%; risk difference, -4.2% [95% CI: -14.8%-6.0%]), and CR rate was significantly higher in zanubrutinib over orelabrutinib (77.9% vs. 42.9%; risk difference, 35.0% [95% CI: 14.5%, 53.7%]). Investigator-assessed PFS was similar with a favorable trend (HR, 0.77 [95% CI: 0.45-1.32]) in zanubrutinib over orelabrutinib and the 12-month PFS rate was numerically higher in zanubrutinib (77.5% vs. 70.8%). MAIC result showed zanubrutinib demonstrated favorable PFS over orelabrutinib for R/R CLL/SLL patients. The naïve comparison showed zanubrutinib had favorable PFS and higher CR rate than orelabrutinib for R/R MCL patients.

Keywords: Indirect treatment comparison; Orelabrutinib; R/R CLL/SLL; R/R MCL; Zanubrutinib.

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Conflict of interest statement

The authors have no relevant financial or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
Progression-free survival in R/R CLL/SLL patients assessed by IRC before and after matching
Fig. 2
Fig. 2
Progression-free survival in R/R MCL patients assessed by the investigator * The HR of PFS is descriptive and for reference only
See this image and copyright information in PMC

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