Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

Ahead of print

doi: 10.17219/acem/159288

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Wang S, Zhu YQ, Qian XH, et al. The outcome of ibrutinib-based regimens in relapsed/refractory central nervous system lymphoma and the potential impact of genomic variants [published online as ahead of print on March 7, 2023]. Adv Clin Exp Med. 2023. doi:10.17219/acem/159288

The outcome of ibrutinib-based regimens in relapsed/refractory central nervous system lymphoma and the potential impact of genomic variants

Shu Wang1,A,B,C,D, Yuqi Zhu2,B,C, Xiaohan Qian1,B,C, Tianling Ding1,C,E, Yan Yuan1,C,E, Yuan Li2,C,E, Hanfeng Wu3,A,B,F, Tong Chen1,A,E,F

1 Department of Hematology, Huashan Hospital, Fudan University, Shanghai, China

2 Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China

3 Department of Neurosurgery, Shanghai Gamma Hospital, China

Abstract

Background. Relapsed/refractory (r/r) central nervous system lymphoma (CNSL) exhibits aggressive behavior and poor outcomes. As an effective bruton tyrosine kinase (BTK) inhibitor, ibrutinib yields benefits in B-cell malignancies.
Objectives. We aimed to explore the efficacy of ibrutinib in treating r/r CNSL patients, and whether genomic variants impact treatment outcomes.
Material and Methods. The ibrutinib-based regimens in 12 r/r primary CNSL (PCNSL) and 2 secondary CNSL (SCNSL) patients were analyzed retrospectively. The impact of genetic variants on the effects of treatments was examined using whole-exome sequencing (WES) technology.
Results. In PCNSL, the overall response rate was 75%, with median overall survival (OS) not reached (NR) and progression-free survival (PFS) of 4 months. Both SCNSL patients responded to ibrutinib, with median OS NR and PFS of 0.5–1.5 months. Infections were common during ibrutinib therapy (42.86%). The PCNSL patients harboring gene mutations in PIM1, MYD88 and CD79B, and the proximal BCR and nuclear factor kappa B (NF-κB) pathways responded to ibrutinib. Patients who harbored simple genetic variants and those with a low tumor mutation burden (TMB; 2.39–5.56/Mb) responded swiftly and maintained remission for more than 10 months. A patient with a TMB of 11/Mb responded to ibrutinib but continued to experience disease progression. In contrast, patients with complex genomic features, especially extremely high TMB (58.39/Mb), responded poorly to ibrutinib.
Conclusion. Our study demonstrates that ibrutinib-based therapy is effective and relatively safe for the treatment of r/r CNSL. Patients with less genomic complexity, especially with regard to TMB, might benefit more from ibrutinib regimens.

Key words

ibrutinib, tumor mutation burden, central nervous system lymphoma, relapsed/refractory, genomic variants

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