Hyperprogression, a challenge of PD-1/PD-L1 inhibitors treatments: potential mechanisms and coping strategies

Liping, Zhao; Hu, Jun-hu; Hu, Die; Wang, Haojie; Huang, Chang-gang; Luo, Ruhua; Zhou, Zhao-huang; Huang, Xin‐Yun; Xie, Tian; Lou, Jian-Shu

doi:10.1016/j.biopha.2022.112949

Cited by 7 publications

(11 citation statements)

References 218 publications

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“…In addition, reports have shown that radiotherapy can activate the immune system by releasing tumor antigens, 7 and after antigen release, dendritic cells take up the antigens and present them to effector T cells, serving as a bridge for systemic immune responses 8 . Zhao et al concluded that the induction of sufficient antigen release by radiotherapy helps to suppress the occurrence of HPD 9 . On the other hand, radiotherapy may stimulate the endogenous expression of PD‐L1 through the induction of IFN‐I secretion 10 .…”

Section: Discussionmentioning

confidence: 99%

Hyperprogressive disease in lung metastases without target lesion progression after durvalumab consolidation therapy: A case report

Masuda,

Nagai,

Amari

et al. 2023

Thoracic Cancer

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Hyperprogressive disease (HPD) is a novel progressive pattern that occurs after immune checkpoint inhibitor (ICI) administration. Here, a 74‐year‐old woman who had undergone right lower lobectomy for lung cancer received curative chemoradiotherapy followed by consolidation therapy with durvalumab for metastatic recurrence confined to the mediastinal lymph nodes. Three weeks later, multiple randomly distributed nodular shadows appeared on chest CT, and thoracoscopic lung biopsy led to the diagnosis of multiple pulmonary metastases. HPD may be suspected when multiple metastases appear in new organs early after the administration of ICIs. This phenomenon may occur not only with ICI monotherapy but also with the administration of ICIs after chemoradiotherapy. Therefore, patients who have received radiation therapy should also be given similar attention early after the administration of ICIs.

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Section: Discussionmentioning

confidence: 99%

Hyperprogressive disease in lung metastases without target lesion progression after durvalumab consolidation therapy: A case report

Masuda,

Nagai,

Amari

et al. 2023

Thoracic Cancer

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“…Research shows that chemotherapy combined with PD-1/PD-L1 inhibitors might suppress HPD, and cytotoxic drugs improve the immune microenvironment, such as the promotion of CD8+ T cell and NK cell infiltration and suppression of regulatory T cells ( 26 ). Meanwhile, chemotherapy can activate the antigen-presenting cell (APC)-mediated antigen presentation process, promoting an anti-tumor immune response to treat HPD ( 8 ). Anti-angiogenic therapy reduces the incidence of HPD upon that the increased VEGF induced by immune inhibitors promotes HPD via angiogenesis ( 8 , 33 , 34 ).…”

Section: Discussionmentioning

confidence: 99%

“…HPD is associated with higher mortality and poor prognosis. There is evidence showing that some unique gene mutations and clinical characteristics, such as being older and the presence of multiple metastases, may be high-risk factors for HPD in different types of cancer ( 8 ). Therefore, it is necessary to pay attention to the risk factors in clinical practice to help patients timely to avoid HPD and make suitable treatment decisions.…”

Section: Introductionmentioning

confidence: 99%

Case report: A combined immunotherapy strategy as a promising therapy for MSI-H colorectal carcinomas with multiple HPD risk factors

Zhang

Yang²,

Kong³

et al. 2023

Front. Med.

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Approximately 5% of advanced colorectal carcinomas (CRCs) and 12–15% of early CRCs are microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors. Nowadays, PD-L1 inhibitors or combined CTLA4 inhibitors are the major strategies for advanced or metastatic MSI-H colorectal cancer, but some people still show drug resistance or progression. Combined immunotherapy has been shown to expand the benefit population in non-small-cell lung carcinoma (NSCLC), hepatocellular carcinoma (HCC), and other tumors while reducing the incidence of hyper-progression disease (HPD). Nevertheless, advanced CRC with MSI-H remains rare. In this article, we describe a case of an elder patient with MSI-H advanced CRC carrying MDM4 amplification and DNMT3A co-mutation who responded to sintilimab plus bevacizumab and chemotherapy as the first-line treatment without obvious immune-related toxicity. Our case provides a new treatment option for MSI-H CRC with multiple risk factors of HPD and highlights the importance of predictive biomarkers in personalized immunotherapy.

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“…Studies have shown that age is a biomarker for HPD, because immunosenescence is age related and characterized by a decline in cell-mediated immune function and a decline in humoral immune response. 51 Some studies have shown that in NSCLC and cervical squamous cell carcinoma, the HPD patients are younger. 52 – 54 Therefore, age cannot be used as an independent biomarker to predict HPD.…”

Section: Host-derived Biomarkersmentioning

confidence: 99%

“…Recent studies have reported that first-line ICIs combination therapy in cancer patients with excellent Eastern Cooperative Oncology Group performance status (ECOG PS = 0) has a better prognosis, with improved PFS and OS. 45 51 Some studies have shown that in NSCLC and cervical squamous cell carcinoma, the HPD patients are younger. [52][53][54] Therefore, age cannot be used as an independent biomarker to predict HPD.…”

Section: Performance Statusmentioning

confidence: 99%

Correlation of preclinical and clinical biomarkers with efficacy and toxicity of cancer immunotherapy

et al. 2023

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Immune checkpoint inhibitors (ICIs) have revealed significant clinical values in different solid tumors and hematological malignancy, changing the landscape for the treatment of multiple types of cancer. However, only a subpopulation of patients has obvious tumor response and long-term survival after ICIs treatment, and many patients may experience other undesirable clinical features. Therefore, biomarkers are critical for patients to choose exact optimum therapy. Here, we reviewed existing preclinical and clinical biomarkers of immunotherapeutic efficacy and immune-related adverse events (irAEs). Based on efficacy prediction, pseudoprogression, hyperprogressive disease, or irAEs, these biomarkers were divided into cancer cell-derived biomarkers, tumor microenvironment-derived biomarkers, host-derived biomarkers, peripheral blood biomarkers, and multi-modal model and artificial intelligence assessment-based biomarkers. Furthermore, we describe the relation between ICIs efficacy and irAEs. This review provides the overall perspective of biomarkers of immunotherapeutic outcome and irAEs prediction during ICIs treatment.

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Hyperprogression, a challenge of PD-1/PD-L1 inhibitors treatments: potential mechanisms and coping strategies

Cited by 7 publications

References 218 publications

Hyperprogressive disease in lung metastases without target lesion progression after durvalumab consolidation therapy: A case report

Hyperprogressive disease in lung metastases without target lesion progression after durvalumab consolidation therapy: A case report

Case report: A combined immunotherapy strategy as a promising therapy for MSI-H colorectal carcinomas with multiple HPD risk factors

Correlation of preclinical and clinical biomarkers with efficacy and toxicity of cancer immunotherapy

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