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Zanubrutinib plus salvage chemotherapy for relapsed or refractory diffuse large B-cell lymphoma.


ABSTRACT:

Introduction

Relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) has poor clinical outcomes when treated with conventional salvage chemotherapy. Monotherapy using zanubrutinib, a selective Bruton's tyrosine kinase (BTK) inhibitor, has achieved modest antitumor effect in R/R DLBCL. Here we aimed to evaluate the efficacy and safety of zanubrutinib plus salvage chemotherapy in R/R DLBCL patients.

Methods

We retrospectively reviewed R/R DLBCL patients who were administered with zanubrutinib plus salvage chemotherapy in our center between January, 2019 and December, 2021. Targeted panel sequencing of 11 lymphoma-related genes was performed on 8 patients with poor responses to zanubrutinib-based chemotherapy.

Results

27 R/R DLBCL patients were enrolled. Median age at this study was 59 years (range, 15-72). The best overall response rate (ORR) was 74.1% and complete remission rate was 33.3%. With a median follow-up of 11 months (range, 1-17), the median progression-free survival (PFS) was 8.1 months, and the overall survival (OS) was not achieved. The most common grade-3/4 adverse events were neutropenia (70.4%), thrombocytopenia (66.7%), and febrile neutropenia (33.3%). In multivariate analysis, early treatment and overall response after chemotherapy were independent favorable prognostic factors for PFS. Overall response after chemotherapy was an independent favorable factor for OS. Among the 8 patients with poor response to zanubrutinib-based treatment, the majority of patients had NOTCH2 mutations (n=8, 100%) and TP53 mutations (n=7, 87.5%). However, these patients achieved an ORR of 75% at 3 months after CD19-CAR-T cell therapy (including 4 cases of complete remission and 2 cases of partial remission). With a median follow-up of 9 months from CAR-T cell infusion (range, 1-16 months), the median PFS was 14.5 months, and the median OS was not reached.

Conclusion

With high efficacy and manageable tolerability, zanubrutinib plus salvage chemotherapy may be a potential treatment option for R/R DLBCL. CAR-T cell therapy may be a priority strategy for these poor responders to BTKi-based treatment.

SUBMITTER: Yuan X 

PROVIDER: S-EPMC9729240 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Zanubrutinib plus salvage chemotherapy for relapsed or refractory diffuse large B-cell lymphoma.

Yuan Xianggui X   Li Xian X   Huang Yurong Y   Jin Xueli X   Liu Hui H   Zhao Aiqi A   Zhang Weiping W   Qian Wenbin W   Liang Yun Y  

Frontiers in immunology 20221124


<h4>Introduction</h4>Relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) has poor clinical outcomes when treated with conventional salvage chemotherapy. Monotherapy using zanubrutinib, a selective Bruton's tyrosine kinase (BTK) inhibitor, has achieved modest antitumor effect in R/R DLBCL. Here we aimed to evaluate the efficacy and safety of zanubrutinib plus salvage chemotherapy in R/R DLBCL patients.<h4>Methods</h4>We retrospectively reviewed R/R DLBCL patients who were administere  ...[more]

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