PMID- 36881367
OWN - NLM
STAT- MEDLINE
DCOM- 20230831
LR  - 20230831
IS  - 1899-5276 (Print)
IS  - 1899-5276 (Linking)
VI  - 32
IP  - 8
DP  - 2023 Aug
TI  - The outcome of ibrutinib-based regimens in relapsed/refractory central nervous 
      system lymphoma and the potential impact of genomic variants.
PG  - 855-863
LID - 10.17219/acem/159288 [doi]
AB  - 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-kappaB) 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. CONCLUSIONS: 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.
FAU - Wang, Shu
AU  - Wang S
AD  - Department of Hematology, Huashan Hospital, Fudan University, Shanghai, China.
FAU - Zhu, Yuqi
AU  - Zhu Y
AD  - Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China.
FAU - Qian, Xiaohan
AU  - Qian X
AD  - Department of Hematology, Huashan Hospital, Fudan University, Shanghai, China.
FAU - Ding, Tianling
AU  - Ding T
AD  - Department of Hematology, Huashan Hospital, Fudan University, Shanghai, China.
FAU - Yuan, Yan
AU  - Yuan Y
AD  - Department of Hematology, Huashan Hospital, Fudan University, Shanghai, China.
FAU - Li, Yuan
AU  - Li Y
AD  - Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China.
FAU - Wu, Hanfeng
AU  - Wu H
AD  - Department of Neurosurgery, Shanghai Gamma Hospital, China.
FAU - Chen, Tong
AU  - Chen T
AD  - Department of Hematology, Huashan Hospital, Fudan University, Shanghai, China.
LA  - eng
PT  - Journal Article
PL  - Poland
TA  - Adv Clin Exp Med
JT  - Advances in clinical and experimental medicine : official organ Wroclaw Medical 
      University
JID - 101138582
RN  - 1X70OSD4VX (ibrutinib)
SB  - IM
MH  - Humans
MH  - Retrospective Studies
MH  - *Lymphoma
MH  - *Central Nervous System Neoplasms/drug therapy/genetics/metabolism
MH  - *Lymphoma, Non-Hodgkin
MH  - Genomics
MH  - Central Nervous System
OTO - NOTNLM
OT  - central nervous system lymphoma
OT  - genomic variants
OT  - ibrutinib
OT  - relapsed/refractory
OT  - tumor mutation burden
EDAT- 2023/03/08 06:00
MHDA- 2023/08/31 06:41
CRDT- 2023/03/07 11:23
PHST- 2023/08/31 06:41 [medline]
PHST- 2023/03/08 06:00 [pubmed]
PHST- 2023/03/07 11:23 [entrez]
AID - 10.17219/acem/159288 [doi]
PST - ppublish
SO  - Adv Clin Exp Med. 2023 Aug;32(8):855-863. doi: 10.17219/acem/159288.