Efficacy and safety of PD‐1 monoclonal antibody plus rituximab in relapsed/refractory diffuse large B cell lymphoma patients

Qin, Yan; He, Xiaohui; Chen, Xinrui; Xie, Zucheng; Yang, Jianliang; Yang, Sheng; Liu, Peng; Zhou, Shengyu; Zhang, Changgong; Gui, Lin; Shi, Yuankai

doi:10.1111/ejh.14013

Cited by 2 publications

(1 citation statement)

References 25 publications

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“…Sample sequencing was performed. The detailed sequencing procedure was described by Qin Y et al study (Qin et al, 2021;Qin et al, 2023).…”

Section: Capture-based Targeted Dna Sequencing and Data Analysismentioning

confidence: 99%

Genetic landscape and prognostic value of IRF4 alterations in Diffuse large B-cell lymphoma patients

Qin,

Chen,

Xie

et al. 2024

Preprint

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Objective: Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell NHL with high heterogeneity. Patients with IRF4 alterations in various hematologic malignancies have a different prognosis. Methods: From January 1st, 2006 to December 31st, 2022, all enrolled novel DLBCL patients treated with R-CHOP or R-CHOP-like regimens underwent high-resolution sequencing based on probe capture, immunohistochemistry and fluorescence in situ hybridization. Publicity datasets were used to validate. Differential expression gene and connectivity map (CMap) analysis were used to screen the potential drugs to improve the clinical outcome. Results: By April 28th, 2023, 324 patients were enrolled, 164 had disease progressed or recurrence, while 160 hadn’t. The number of patients in each group who had mutations in TP53, MYD88, BCL2, IRF4, STAT3, BCOR, ID3, and CD79A varied significantly. TP53 and IRF4 mutations (mPFS of mutation vs. wildtype: 33.93 vs. 11.17 months, p=0.018, HR:0.60, 95%CI:0.35-1.01) were found to be significantly associated with poor survival, according to univariate and multivariable analysis. Subgroup analysis showed that for IRF4mut GCB/nonGCB and IRF4wt GCB/nonGCB patients had significantly different PFS (p=0.002, HR:2.92, 95%CI: 1.05-8.10). Pairwise comparisons analysis show that the IRF4mutnonGCB subtype is significantly associated with shorter PFS in both our cohort and validation cohort (p=0.001). According to CMap , IRF4mut patients may benefit from regimens containing lenalidomide, ibrutinib, or mitoxantrone as first- and subsequent-line treatment options. Conclusions: This study comprehensively described the genetic landscape of novel DLBCL. IRF4 mutation is an independent prognostic factor in DLBCL patients, and PFS is significantly shortened in IRF4mut nonGCB DLBCL subtype.

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“…Sample sequencing was performed. The detailed sequencing procedure was described by Qin Y et al study (Qin et al, 2021;Qin et al, 2023).…”

Section: Capture-based Targeted Dna Sequencing and Data Analysismentioning

confidence: 99%

Genetic landscape and prognostic value of IRF4 alterations in Diffuse large B-cell lymphoma patients

Qin,

Chen,

Xie

et al. 2024

Preprint

Self Cite

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Multi-omics analysis and response prediction of PD-1 monoclonal antibody containing regimens in patients with relapsed/refractory diffuse large B-cell lymphoma

Chen,

Qin,

Xue

et al. 2024

Cancer Immunol Immunother

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Patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) show varied responses to PD-1 monoclonal antibody (mAb) containing regimens. The mechanisms and predictive biomarkers for the efficacy of this regimen are unclear. This study retrospectively collected r/r DLBCL patients who received PD-1 mAb and rituximab regimens as salvage therapy. Clinical and genomic features were collected, and mechanisms were explored by multiplex immunofluorescence and digital spatial profiling. An artificial neural network (ANN) model was constructed to predict the response. Between October 16th, 2018 and May 4th, 2023, 50 r/r DLBCL patients were collected, 29 were response patients and 21 were non-response patients. CREBBP ( p = 0.029) and TP53 ( p = 0.015) alterations were statistically higher in non-response patients. Patients with PD-L1 CPS ≥ 5 were correlated with a longer overall survival (OS) than those with PD-L1 CPS < 5 (median OS: not reached vs. 9.7 months, hazard ratio [HR]: 3.8, 95% confidence interval [CI] 0.64–22.44, p = 0.016). Immune-related pathways were activated in response patients. The proportion and spatial organization of tumor-infiltrating immune cells affect the response. PD-L1 CPS level, age, and alterations of TP53 , MYD88 , CREBBP , EP300 , GNA13 were used to build an ANN predictive model that showed high prediction efficiency (training set area under curve [AUC] of 0.97 and test set AUC of 0.94). The proportion and spatial distribution of tumor-infiltrating immune cells may be related to the function of immune-related pathways, thereby influencing the efficacy of PD-1 mAb containing regimens. The ANN predictive model showed potential value in predicting the responses of r/r DLBCL patients received PD-1 mAb and rituximab regimens. Supplementary Information The online version contains supplementary material available at 10.1007/s00262-024-03840-0.

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Efficacy and safety of PD‐1 monoclonal antibody plus rituximab in relapsed/refractory diffuse large B cell lymphoma patients

Cited by 2 publications

References 25 publications

Genetic landscape and prognostic value of IRF4 alterations in Diffuse large B-cell lymphoma patients

Genetic landscape and prognostic value of IRF4 alterations in Diffuse large B-cell lymphoma patients

Multi-omics analysis and response prediction of PD-1 monoclonal antibody containing regimens in patients with relapsed/refractory diffuse large B-cell lymphoma

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