Efficacy of programmed cell death 1 inhibitor maintenance therapy after combined treatment with programmed cell death 1 inhibitors and anti‐CD19‐chimeric antigen receptor T cells in patients with relapsed/refractory diffuse large B‐cell lymphoma and high tumor burden

Mu, Juan; Deng, Haobin; Li, Qing; Yuan, Jijun; Li, Qing; Wang, Jia; Jiang, Yanyu; Deng, Qi; Shen, J.Z.

doi:10.1002/hon.2981

Cited by 8 publications

(6 citation statements)

References 32 publications

(65 reference statements)

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“…Similar phenomena have been observed in other cancers (Burr et al, 2019;Ennishi, Takata, et al, 2019). Therefore, ICBT is usually ineffective against DLBCL, though some studies have reported its successful use in r/ rDLBCL (Xu-Monette et al, 2018;Mu et al, 2022). It is thus speculated that an inflammatory environment favourable to ICBT might exist in some cases of DLBCL.…”

Section: Introductionsupporting

confidence: 53%

Gene set-based identification of two immune subtypes of diffuse large B cell lymphoma for guiding immune checkpoint blocking therapy

Duan²,

Ke³

et al. 2022

Front. Genet.

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Background: Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma in adults. Tumour microenvironment is closely related to tumour prognosis and immune checkpoint blocking therapy (ICBT). This study aimed to investigate the immunological and prognostic characteristics of the tumour microenvironment (TME), as well as the regulatory mechanisms.Methods: Gene expression profiles and clinical data of patients with DLBCL were obtained from GEO database. ESTIMATE, CIBERSORT, and ssGSEA analyses were used to explore microenvironment characteristics and regulatory mechanism of the immune subtypes, which were identified by consistent clustering. The differences in enriched pathways were showed by GSEA. Hub genes associated with CD8+ T cells, which were identified by WCGNA, were exhibited biological functions through GO and KEGG. Immune-related gene scores (IRGSs) based on hub genes were used to evaluate the prediction of immune subtypes and ICBT, and retrospective analysis was used for validation. Finally, prognostic genes were screened to construct risk models.Results: Consensus clustering divided patients with DLBCL into two subtypes with significant heterogeneities in prognosis and immune microenvironment. Low immune infiltration was associated with poor prognosis. Subtype C1 with high immune infiltration was enriched in multiple immune pathways. We observed that two common mutated genes (B2M and EZH2) in DLBCL were closely related to MHC-I and microenvironment. Our further analysis manifested that MYD88L265P may be the main cause of TLR signalling pathway activation in subtype C1. Hub genes (SH2D1A, CD8A, GBP2, ITK, CD3D, RORA, IL1R2, CD28, CD247, CD3G, PRKCQ, CXCR6, and CD3E) in relation with CD8+ T cells were used to establish IRGS, which was proved an accurate predictor of immune subtypes, and patients in high-IRGS group were more likely to benefit from ICBT. Retrospective analysis showed that absolute lymphocyte count (ALC) was higher in the group that responded to the PD-1 inhibitor. Finally, the risk model was constructed based on two genes (CD3G and CD3D), and the low-risk group showed better prognosis.Conclusion: DLBCL immune classifications with highly heterogeneity are a powerful predictor of prognosis and ICBT. The IRGS is proved to be a reliable tool to distinguish immune subtypes as a substitute for gene expression profile.

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Section: Introductionsupporting

confidence: 53%

Gene set-based identification of two immune subtypes of diffuse large B cell lymphoma for guiding immune checkpoint blocking therapy

Duan²,

Ke³

et al. 2022

Front. Genet.

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“…The ORR was 64.71%, but the CR was changed to 64.71%, because some patients who obtained PR in CAR-T therapy become CR after the following radiotherapy. In our previous study [27], R/R DLBCL who had high tumor bulk and at least one tumor with a maximum diameter of ≥ 7.5 cm obtained 62.11% ORR and 38.89% CR in their anti-CD19-CAR T-cell therapy. Compared with our previous study, the R-C group improved ORR and CR, while the C-R group did not improve ORR, but the CR proportion was signi cantly increased.…”

Section: Discussionmentioning

confidence: 88%

To compare the efficacy and safety of radiotherapy before and after anti-CD19-CAR T-cell therapy in patients withrelapsed/refractory DLBCL

et al. 2022

Preprint

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Background: What is the difference in efficacy and side effects of radiotherapy bridging CAR-T therapy versus CAR-T therapy followed by radiotherapy? Patients and methods: Fourteen R/R DLBCL patients received radiotherapy before CAR-T therapy (R-C group). R-C group was divided into: 1-3 months radiotherapy before CAR-T therapy (1-3 mons) group and more than 3 months before CAR-T therapy (more than 3 mons) group. Seventeen patients received radiotherapy 2-3 months after CAR-T therapy (C-R) group. Results: In R-C group, ORR was 81.82% and CR was 54.55%. In C-R group, ORR was 64.71% and CR was only 35.29% after CAR-T therapy, but CR became 64.71% after the following radiotherapy. CAR-T cell peaks were higher in R-C group than in C-R group, and higher in R-C (1-3 mons) group than that in R-C (more than 3 mons) group. Three patients in R-C group died of CRS, no patient in C-R group died of CRS. There was no difference in CRS and ICANS in R-C and C-R group. CRS and ICANS grades were higher in R-C (1-3 mons) group than that in R-C (more than 3 mons) group. Conclusions: Radiotherapy bridging CAR-T therapy had higher ORR. While, CAR-T therapy followed by radiotherapy might improve CR without higher CRS and ICANS. Trial registration number ChiCTR1800019622.

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“…Mu et al ( 2022) conducted a study involving forty-four patients with relapsed/refractory (R/R) DLBCL to assess the safety and efficacy of combining PD-1 inhibitors with anti-CD19 CAR-T cell therapy, followed by PD-1 inhibitor maintenance therapy in DLBCL patients with high tumor burden (138). These patients were divided into two groups: a combination group of twenty-six patients and a control group of eighteen patients.…”

Section: Cd-19 Directed Car-t Cell Based Combination Immunotherapymentioning

confidence: 99%

The synergistic immunotherapeutic impact of engineered CAR-T cells with PD-1 blockade in lymphomas and solid tumors: a systematic review

Satapathy,

Sheoran,

Yadav

et al. 2024

Front. Immunol.

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Currently, therapies such as chimeric antigen receptor-T Cell (CAR-T) and immune checkpoint inhibitors like programmed cell death protein-1 (PD-1) blockers are showing promising results for numerous cancer patients. However, significant advancements are required before CAR-T therapies become readily available as off-the-shelf treatments, particularly for solid tumors and lymphomas. In this review, we have systematically analyzed the combination therapy involving engineered CAR-T cells and anti PD-1 agents. This approach aims at overcoming the limitations of current treatments and offers potential advantages such as enhanced tumor inhibition, alleviated T-cell exhaustion, heightened T-cell activation, and minimized toxicity. The integration of CAR-T therapy, which targets tumor-associated antigens, with PD-1 blockade augments T-cell function and mitigates immune suppression within the tumor microenvironment. To assess the impact of combination therapy on various tumors and lymphomas, we categorized them based on six major tumor-associated antigens: mesothelin, disialoganglioside GD-2, CD-19, CD-22, CD-133, and CD-30, which are present in different tumor types. We evaluated the efficacy, complete and partial responses, and progression-free survival in both pre-clinical and clinical models. Additionally, we discussed potential implications, including the feasibility of combination immunotherapies, emphasizing the importance of ongoing research to optimize treatment strategies and improve outcomes for cancer patients. Overall, we believe combining CAR-T therapy with PD-1 blockade holds promise for the next generation of cancer immunotherapy.

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Efficacy of programmed cell death 1 inhibitor maintenance therapy after combined treatment with programmed cell death 1 inhibitors and anti‐CD19‐chimeric antigen receptor T cells in patients with relapsed/refractory diffuse large B‐cell lymphoma and high tumor burden

Cited by 8 publications

References 32 publications

Gene set-based identification of two immune subtypes of diffuse large B cell lymphoma for guiding immune checkpoint blocking therapy

Gene set-based identification of two immune subtypes of diffuse large B cell lymphoma for guiding immune checkpoint blocking therapy

To compare the efficacy and safety of radiotherapy before and after anti-CD19-CAR T-cell therapy in patients withrelapsed/refractory DLBCL

The synergistic immunotherapeutic impact of engineered CAR-T cells with PD-1 blockade in lymphomas and solid tumors: a systematic review

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