Predicting Responses to Checkpoint Inhibitors in Lymphoma: Are We Up to the Standards of Solid Tumors?

Jeong, Ah-Reum; Ball, Edward D.; Goodman, Aaron M.

doi:10.1177/1179554920976366

Cited by 8 publications

(10 citation statements)

References 98 publications

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“…Factors include immunogenic neoantigen generation, immunoselection favoring antigenic mutant proteins, and the tumor microenvironment affecting T-cell infiltration and activation. TMB’s relation to PD-1/PD-L1 ICB response in hematological malignancies is evolving ( 10 , 26 ). The median TMB in hematological malignancies is approximately 1.7 mut/Mb, with lymphoma TMB varying due to multiple factors ( 10 , 26 ).…”

Section: Discussionmentioning

confidence: 99%

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Case report: From sequence to solution: tailoring treatment for transformed follicular lymphoma (DLBCL) through next generation sequencing study

Bouroumeau,

Perdikis-Prati,

Lang

2024

Front. Oncol.

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Immune checkpoint blockade (ICB) has indeed transformed the outlook for many advanced-stage solid tumors, yet its effectiveness in hematological malignancies has been particularly limited, with success predominantly demonstrated in classical Hodgkin lymphoma (cHL) and immune-privilege subtypes of non-Hodgkin lymphoma (NHL). In this report, we present an impactful case of a 71-year-old man grappling with refractory follicular lymphoma (rFL) that had progressed to a high-grade lymphoma, leaving no conventional treatment options on the table. Notably, the histological examination of the tumor tissue revealed a markedly elevated PD-L1 expression, illuminating the potential for immunotherapy to be effective. Additionally, comprehensive gene sequencing unveiled a moderate tumor mutational burden (TMB), deepening our understanding of the tumor’s molecular intricacies. As his health declined with no access to cell therapies or clinical trials at that time, a combination treatment of PD-1 ICB and an anti-CD20 drug surprisingly led to a significant improvement in his condition and long-term remission. While PD-1 ICB therapy has historically shown limited responses in non-Hodgkin lymphomas (NHLs), this case serves as a beacon of optimism, underscoring the promise of combining immunotherapy modalities and the potential of comprehensive molecular assessments in charting innovative treatments for extensively treated NHL patients. The quest for predictive biomarkers to gauge treatment response remains a formidable challenge. This report serves as a testament to the ever-evolving landscape of cancer treatment, where precision medicine and immunotherapy continue to unlock new possibilities for those confronting the most challenging malignancies.

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Section: Discussionmentioning

confidence: 99%

“…TMB’s relation to PD-1/PD-L1 ICB response in hematological malignancies is evolving ( 10 , 26 ). The median TMB in hematological malignancies is approximately 1.7 mut/Mb, with lymphoma TMB varying due to multiple factors ( 10 , 26 ). In FL, Chalmers et al.…”

Section: Discussionmentioning

confidence: 99%

Case report: From sequence to solution: tailoring treatment for transformed follicular lymphoma (DLBCL) through next generation sequencing study

Bouroumeau,

Perdikis-Prati,

Lang

2024

Front. Oncol.

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“…Several cancer types, notably those with MSI, can benefit from the use of TMB as a promising biomarker for predicting the susceptibility to immune checkpoint inhibitor therapies. [30,34] The potential relationship between the NT5E expression and TMB/MSI in different cancers was assessed in this study. These findings suggest that NT5E may serve as a novel target for cancer immunotherapy in cancers like GBM, ESCA, SARC, PAAD, UCEC, THYM, and COAD.…”

Section: Discussionmentioning

confidence: 99%

CD73/NT5E is a Potential Biomarker for Cancer Prognosis and Immunotherapy for Multiple Types of Cancers

Xie

et al. 2022

Advanced Biology

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Cluster of Differentiations 73 (CD73)/ecto‐5'‐nucleotidase (NT5E) is a novel type of immune molecular marker expressed on many tumor cells and involved in regulating the essential immune functions and affecting the prognosis of cancer patients. However, it is not clear how the NT5E is linked to the infiltration levels of the immune cells in pan‐cancer patients and their final prognosis. This study explores the role of NT5E in 33 tumor types using GEPIA, TIMER, Oncomine, BioGPS databases, and several bioinformatic tools. The findings reveal that the NT5E is abnormally expressed in a majority of the types of cancers and can be used for determining the prognosis prediction ability of different cancers. Moreover, NT5E is significantly related to the infiltration status of numerous immune cells, immune‐activated pathways, and immunoregulator expressions. Last, specific inhibitor molecules, like NORNICOTINE, AS‐703026, and FOSTAMATINIB, which inhibit the expression of NT5E in various types of cancers, are screened with the CMap. Thus, it is proposed that NT5E can be utilized as a potential biomarker for predicting the prognosis of cancer patients and determining the infiltration of various immune cells in different types of cancers.

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“…A few studies have aimed to assess predictors of ICI efficacy and toxicity in patients with ML [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. In contrast, most studies have sought to identify factors associated with the clinical efficacy and/or toxicity of CAR T cells.…”

Section: Introductionmentioning

confidence: 99%

Predictive Factors of Response to Immunotherapy in Lymphomas: A Multicentre Clinical Data Warehouse Study (PRONOSTIM)

Detroit,

Collier,

Beeker

et al. 2023

Cancers

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Immunotherapy (IT) is a major therapeutic strategy for lymphoma, significantly improving patient prognosis. IT remains ineffective for a significant number of patients, however, and exposes them to specific toxicities. The identification predictive factors around efficacy and toxicity would allow better targeting of patients with a higher ratio of benefit to risk. PRONOSTIM is a multicenter and retrospective study using the Clinical Data Warehouse (CDW) of the Greater Paris University Hospitals network. Adult patients with Hodgkin lymphoma or diffuse large-cell B lymphoma treated with immune checkpoint inhibitors or CAR T (Chimeric antigen receptor T) cells between 2017 and 2022 were included. Analysis of covariates influencing progression-free survival (PFS) or the occurrence of grade ≥3 toxicity was performed. In total, 249 patients were included. From this study, already known predictors for response or toxicity of CAR T cells such as age, elevated lactate dehydrogenase, and elevated C-Reactive Protein at the time of infusion were confirmed. In addition, male gender, low hemoglobin, and hypo- or hyperkalemia were demonstrated to be potential predictive factors for progression after CAR T cell therapy. These findings prove the attractiveness of CDW in generating real-world data, and show its essential contribution to identifying new predictors for decision support before starting IT.

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Predicting Responses to Checkpoint Inhibitors in Lymphoma: Are We Up to the Standards of Solid Tumors?

Cited by 8 publications

References 98 publications

Case report: From sequence to solution: tailoring treatment for transformed follicular lymphoma (DLBCL) through next generation sequencing study

Case report: From sequence to solution: tailoring treatment for transformed follicular lymphoma (DLBCL) through next generation sequencing study

CD73/NT5E is a Potential Biomarker for Cancer Prognosis and Immunotherapy for Multiple Types of Cancers

Predictive Factors of Response to Immunotherapy in Lymphomas: A Multicentre Clinical Data Warehouse Study (PRONOSTIM)

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