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Ibrutinib combined with venetoclax for the treatment of relapsed/refractory diffuse large B cell lymphoma

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Abstract

Treatment outcomes of relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) are far from satisfactory. Certain efficacy of ibrutinib has been observed in non-GCB subtype DLBCL patients. This study aimed to investigate the efficacy and safety of ibrutinib plus BCL2 inhibitor venetoclax in R/R DLBCL patients with non-GCB subtype and BCL2 overexpression. Combinational therapy (ibrutinib 560mg/day; venetoclax started 1 week later, oral dose increased from 100 to 400mg/day in 3 weeks) was conducted, and one cycle was 4 weeks. Both drugs were stopped when disease progress or serious adverse reactions appear. The primary end-point was overall response rate (ORR) at two cycles. From December 2018 to July 2020, a total of 13 patients were treated with the combined therapy. Among them, eleven (84.6%) patients previously received at least two treatment regimens, eight (61.5%) patients were C-myc and BCL2 double expression. The ORR at two cycles was 61.5%, with 3 (23.1%) patients achieved complete remission (CR) and 5 (38.4%) patients achieved partial remission (PR). The ORR at four cycles and six cycles was 53.8% and 46.2%, respectively. The median duration of response was 11 months (range, 1.5–13.6 months). The median progression-free survival and overall survival were 5.6 months (range, 0.4–15.6) and 11.3 months (range, 2.8–17.2), respectively. The most common adverse event was grade 1/2 neutropenia (53.8%), and nonhematologic toxicities included Grade1/2 diarrhea (46.2%) and elevated liver enzymes (30.8%). Combined therapy of ibrutinib and venetoclax showed promising efficacy and synergistic effects in R/R DLBCL patients with non-GCB subtype and BCL2 overexpression, and the toxicities were well-tolerated.

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Funding

This work was supported by the Scientific and Technological Research Projects in Henan Province No. 202102310106.

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Authors and Affiliations

  1. Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, China

    Zhiyuan Zhou, Lei Zhang, Xinhua Wang, Xin Li, Ling Li, Xiaorui Fu, Xudong Zhang, Zhaoming Li, Zhenchang Sun & Mingzhi Zhang

  2. Lymphoma Diagnosis and Treatment Center of Henan Province, No. 1 Jianshe East Road, Zhengzhou, China

    Zhiyuan Zhou, Lei Zhang, Xinhua Wang, Xin Li, Ling Li, Xiaorui Fu, Xudong Zhang, Zhaoming Li, Zhenchang Sun & Mingzhi Zhang

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  1. Zhiyuan Zhou
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  2. Lei Zhang
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  3. Xinhua Wang
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  4. Xin Li
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  5. Ling Li
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  10. Mingzhi Zhang
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Contributions

Zhiyuan Zhou, Mingzhi Zhang: design the study and wrote the manuscript. Lei Zhang, Xinhua Wang, Xin Li, Ling Li, Xiaorui Fu, Xudong Zhang, Zhaoming Li, Zhenchang Sun: co-investigators, gathered and interpreted data. All authors reviewed and approved the final version of the report.

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Correspondence to Mingzhi Zhang.

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Zhou, Z., Zhang, L., Wang, X. et al. Ibrutinib combined with venetoclax for the treatment of relapsed/refractory diffuse large B cell lymphoma. Ann Hematol 100, 1509–1516 (2021). https://doi.org/10.1007/s00277-021-04535-7

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