Chinese expert consensus on Bruton tyrosine kinase inhibitors in the treatment of B-cell malignancies

Song, Yuqin; Wu, Shang-Ju; Shen, Zhixiang; Zhao, Donglu; Chan, Thomas Sau Yan; Huang, Huiqiang; Qiu, Lugui; Li, Jianyong; Tan, Tran-der; Zhu, Jun; Song, Yongping; Huang, Wei-Han; Zhao, Weili; Liu, Herman Sung Yu; Xu, Wei; Chen, Naizhi; Ma, Jun; Chang, Cheng-Shyong; Tse, Eric Wai Choi

doi:10.1186/s40164-023-00448-5

Experimental Hematology & Oncology

Table 5 Evidence of BTK inhibitors in patients with DLBCL

From: Chinese expert consensus on Bruton tyrosine kinase inhibitors in the treatment of B-cell malignancies

Patients type	Treatment regimen	Efficacy	Study	Phase	N
Non-GCB
TN	Ibrutinib + R-CHOP (rituximab 375 mg/m², cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², vincristine 1.4 mg/m², and oral prednisone [or equivalent] 100 mg) vs. placebo + R-CHOP	36-month PFS rate: 70.8% vs. 68.1%; 36-month OS rate: 82.8% vs. 81.4%; CR rate: 67.3% v 68.0%	PHOENIX [79]	3	419 vs. 419
TN, ≤ 65 years	Acalabrutinib + R-CHOP	Ongoing	ESCALADE [80]	3	600
R/R	Zanubrutinib	ORR, non-GCB: 36%, GCB: 25%	BGB-3111–207 [83]	2	29
R/R, ASCT ineligible	Zanubrutinib + lenalidomide	Best ORR: 90.9%, CR: 36.4% Study ongoing	BGB-3111–110 [84]	1	27
R/R	Ibrutinib	ORR, non-GCB: 37%, GCB: 5%	NCT00849654 NCT01325701 [85]	2	80
R/R	Acalabrutinib	ORR, non-GCB: 24% (5/21); 4 CR and 1 PR	NCT02112526 [86]	1b	21
BCL2/MYC expression
TN	Ibrutinib + R-CHOP	DE: CR: 67.5%; PR 22.8%	PHOENIX, post hoc [174]	3	200
R/R	Ibrutinib	DE: ORR 47%; CR 37%	Landsburg et al. [90]	Case-series	25
R/R	Zanubrutinib	DE: ORR 61%; NDE: ORR 29%	BGB-3111–207 [83]	Post-hoc	121
TN	Zanubrutinib + R-CHOP	Ongoing	NCT05189197 [92]	2	41
CD79B, MYD88 (MCD)
TN	Ibrutinib + R-CHOP	MCD and aged ≤ 60 years: 3-year EFS and OS: 100%	PHOENIX, post hoc [94]	3	31
TN	Orelabrutinib + R-CHOP	Ongoing	NCT05234684 [95]	3	150
R/R	Zanubrutinib	CD79B mutation: ORR 46%; MYD88 mutation: ORR 40%; MYD88 + CD79B (MCD) mutation: ORR 50%	BGB-3111–207 [83]	2	41
Elderly and unfit/frail
TN	Ibrutinib + rituximab + lenalidomide	ORR 66.7%; CR rate: 56.7%; 2-year PFS rate: 53·3%; 2-year OS rate: 66·7%	NCT03949062 [99]	2	30
TN	Zanubrutinib + rituximab + lenalidomide vs. R-mini-CHOP (rituximab 375 mg/m² on day 1, cyclophosphamide 400 mg/m², doxorubicin 25 mg/m², and vincristine 1 mg on day 2, and prednisone 40 mg/m² on days 2–6, every 21 days)	Ongoing	NCT05179733 [100]	3	280

ASCT, autologous stem cell transplantation; BCL2, B-cell lymphoma 2; BTK, Bruton tyrosine kinase; CR, complete response; DE, double expressor, DLBCL, diffuse large B-cell lymphoma; EFS, event-free survival; GCB, germinal center B cell; MYC, myelocytomatosis oncogene; NDE, non-double expressor; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; R/R, relapsed/refractory; TN, treatment naïve

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ISSN: 2162-3619

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