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<p>In diffuse large B-cell lymphoma (DLBCL), although most patients are curable, the approximately one-third who experience refractory or relapsed disease face a poor prognosis, underscoring the need for novel therapeutic strategies. Although Bruton’s tyrosine kinase inhibitors (BTKis) exhibit anti-lymphoma activity in various B-cell malignancies, they are less effective in patients with the germinal center B-cell-like (GCB) subtype. The anti-CD79b antibody-drug conjugate polatuzumab vedotin has been approved for DLBCL treatment. Previous studies have shown that the combination of the second-generation BTKi zanubrutinib and polatuzumab vedotin, within the R-CHOP regimen, yielded higher response rates in preliminary clinical studies; however, the efficacy of this combination remains unclear. This study aimed to evaluate whether zanubrutinib plus polatuzumab vedotin could represent a novel therapeutic approach. Through assays of drug combination, cell proliferation, cell cycle, and apoptosis, we demonstrated that this combination synergistically inhibited DLBCL cell proliferation both in vitro and in vivo. Moreover, zanubrutinib enhanced polatuzumab vedotin-induced G<sub>2</sub>/M phase arrest and apoptosis in DLBCL cells, accompanied by increased CD79b expression. Notably, the combination showed superior synergistic efficacy in GCB-subtype cells. In conclusion, these findings provide a novel mechanistic rationale for combining zanubrutinib and polatuzumab vedotin in DLBCL treatment, regardless of cell-of-origin subtype.</p>

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Zanubrutinib potentiates polatuzumab vedotin efficacy in DLBCL with concurrent CD79b upregulation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月19日

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  • Xiaolong Zhou,
  • Jingjing Li,
  • Zipeng Zhao,
  • Jie Liu,
  • Junyi Zhang,
  • Wen Zhou,
  • Ailing Gui,
  • Yichen Yan,
  • Shun Zhu,
  • Wen Liu,
  • Ji Zuo,
  • Qunling Zhang,
  • Ling Yang

摘要

In diffuse large B-cell lymphoma (DLBCL), although most patients are curable, the approximately one-third who experience refractory or relapsed disease face a poor prognosis, underscoring the need for novel therapeutic strategies. Although Bruton’s tyrosine kinase inhibitors (BTKis) exhibit anti-lymphoma activity in various B-cell malignancies, they are less effective in patients with the germinal center B-cell-like (GCB) subtype. The anti-CD79b antibody-drug conjugate polatuzumab vedotin has been approved for DLBCL treatment. Previous studies have shown that the combination of the second-generation BTKi zanubrutinib and polatuzumab vedotin, within the R-CHOP regimen, yielded higher response rates in preliminary clinical studies; however, the efficacy of this combination remains unclear. This study aimed to evaluate whether zanubrutinib plus polatuzumab vedotin could represent a novel therapeutic approach. Through assays of drug combination, cell proliferation, cell cycle, and apoptosis, we demonstrated that this combination synergistically inhibited DLBCL cell proliferation both in vitro and in vivo. Moreover, zanubrutinib enhanced polatuzumab vedotin-induced G2/M phase arrest and apoptosis in DLBCL cells, accompanied by increased CD79b expression. Notably, the combination showed superior synergistic efficacy in GCB-subtype cells. In conclusion, these findings provide a novel mechanistic rationale for combining zanubrutinib and polatuzumab vedotin in DLBCL treatment, regardless of cell-of-origin subtype.