Effect of ibrutinib with R-CHOP chemotherapy in genetic subtypes of DLBCL

Wilson, Wyndham H.; Wright, George W.; Huang, Da Wei; Hodkinson, Brendan P.; Balasubramanian, Sriram; Fan, Yue; Vermeulen, Jessica; Shreeve, Martin; Staudt, Louis M.

doi:10.1016/j.ccell.2021.10.006

Cited by 188 publications

(167 citation statements)

References 90 publications

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“…Very recently, after analysis of biopsies from Phoenix trial, Wilson. et al reported that the 3-year event-free survival of younger patients treated with ibrutinib plus R-CHOP was 100% in the MCD subtypes, which provide solid evidence of the efficacy of ibrutinib in DLBCL (3) .…”

Section: Introductionmentioning

confidence: 95%

Preliminary Evaluation of Zanubrutinib-Containing Regimens in DLBCL and the Cerebrospinal Fluid Distribution of Zanubrutinib: A 13-Case Series

Zhang

Zhuang

et al. 2021

Front. Oncol.

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Zanubrutinib is a second-generation Bruton’s tyrosine kinase inhibitor. Its safety and effectiveness in central nervous system (CNS) lymphoma along with its distribution in the brain and ability to cross the blood–brain barrier (BBB) remain unknown. This retrospective case series involved patients with diffuse large B-cell lymphoma (DLBCL) treated with zanubrutinib-containing regimens from August to December 2020 in PUMCH. The amounts of zanubrutinib in the plasma and brain were assessed by liquid chromatography–tandem mass spectrometry in paired plasma and cerebrospinal fluid (CSF) samples. In total, 13 patients were included: eight primary CNS lymphoma cases and five systemic DLBCL cases with 61.5% (8/13) refractory/relapsed and 84.6% (11/13) showing CNS involvement. The overall response rates were 84.5% in the entire population and 81.8% in the CNS-involved cases. A total of 23 time-matched plasma-CSF sample pairs were collected. The mean peak concentration of zanubrutinib in CSF was 2941.1 pg/ml (range, 466–9032.0 pg/ml). The corrected mean CSF/plasma ratio determined based on 94% protein binding was 42.7% ± 27.7% (range, 8.6%–106.3%). This preliminary study revealed the effectiveness of zanubrutinib-containing regimens in DLBLC, especially CNS-involved cases, for the first time. The excellent BBB penetration of zanubrutinib supports its further investigation for the treatment of CNS lymphoma.

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Section: Introductionmentioning

confidence: 95%

Preliminary Evaluation of Zanubrutinib-Containing Regimens in DLBCL and the Cerebrospinal Fluid Distribution of Zanubrutinib: A 13-Case Series

Zhang

Zhuang

et al. 2021

Front. Oncol.

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Section: Introductionmentioning

confidence: 99%

“…In a retrospective analysis of PHOENIX trial biopsies, Wilson et al (2021) investigated the presence of DLBCL genetic subtypes to further explore this finding [ 18 ]. Investigators found that survival benefit among patients receiving ibrutinib + R-CHOP was more pronounced within specific genetic subtypes (MCD and N1) [ 18 , 19 ], common in younger patient participants with ABC-COO. These findings offer preliminary evidence of a biological mechanism for the increased benefit of ibrutinib for patients under 60 with specific genetic subtypes common among the ABC subtype of DLBCL [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…Investigators found that survival benefit among patients receiving ibrutinib + R-CHOP was more pronounced within specific genetic subtypes (MCD and N1) [ 18 , 19 ], common in younger patient participants with ABC-COO. These findings offer preliminary evidence of a biological mechanism for the increased benefit of ibrutinib for patients under 60 with specific genetic subtypes common among the ABC subtype of DLBCL [ 18 ]. As suggested by emerging evidence, age-stratified evaluation of ibrutinib + R-CHOP for patients diagnosed with ABC subtype is a promising area for future investigation [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…These findings offer preliminary evidence of a biological mechanism for the increased benefit of ibrutinib for patients under 60 with specific genetic subtypes common among the ABC subtype of DLBCL [ 18 ]. As suggested by emerging evidence, age-stratified evaluation of ibrutinib + R-CHOP for patients diagnosed with ABC subtype is a promising area for future investigation [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cost-Effectiveness of Molecularly Guided Treatment in Diffuse Large B-Cell Lymphoma (DLBCL) in Patients under 60

Regier

Chan²,

Costa³

et al. 2022

Cancers

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Background: Classifying diffuse large B-cell lymphoma (DLBCL) into cell-of-origin (COO) subtypes could allow for personalized cancer control. Evidence suggests that subtype-guided treatment may be beneficial in the activated B-cell (ABC) subtype of DLBCL, among patients under the age of 60. Methods: We estimated the cost-effectiveness of age- and subtype-specific treatment guided by gene expression profiling (GEP). A probabilistic Markov model examined costs and quality-adjusted life-years gained (QALY) accrued to patients under GEP-classified COO treatment over a 10-year time horizon. The model was calibrated to evaluate the adoption of ibrutinib as a first line treatment among patients under 60 years with ABC subtype DLBCL. The primary data source for efficacy was derived from published estimates of the PHOENIX trial. These inputs were supplemented with patient-level, real-world data from BC Cancer, which provides comprehensive cancer services to the population of British Columbia. Results: We found the cost-effectiveness of GEP-guided treatment vs. standard care was $77,806 per QALY (24.3% probability of cost-effectiveness at a willingness-to-pay (WTP) of $50,000/QALY; 53.7% probability at a WTP of $100,000/QALY) for first-line treatment. Cost-effectiveness was dependent on assumptions around decision-makers’ WTP and the cost of the assay. Conclusions: We encourage further clinical trials to reduce uncertainty around the implementation of GEP-classified COO personalized treatment in this patient population.

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