Nivolumab plus ipilimumab combination therapy in cancer: Current evidence to date

Nikoo, Marzieh; Rabiee, Fatemeh; Mohebbi, Hossein; Eghbalifard, Negar; Rajabi, Hamid; Yazdani, Yalda; Sakhaei, Delaram; Khosravifarsani, Mohammadreza; Akhavan‐Sigari, Reza

doi:10.1016/j.intimp.2023.109881

Cited by 11 publications

(5 citation statements)

References 203 publications

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“…The IFN signaling system is essential in modulating tumor immunogenicity and has been known to enhance tumor sensitivity to ICIs by inducing PD-L1 expression [29]. While PD-L1 expression may promote tumor susceptibility to ICIs, aberrant IFN-␥ signaling-induced adaptive PD-L1 expression on cancer cells also results in T cell inactivation, which mediates resistance to anti-CTLA-4 therapy or PD1/PD-L1 inhibitors [30]. Further, our study provided insight into several metabolic pathways, including glycolysis, adipogenesis, and reactive oxygen species, which were enriched in the 'no clinical benefit' cohort.…”

Section: Discussionmentioning

confidence: 99%

Genomic and Transcriptomic Characteristics of Tumors of Patients with Metastatic Clear Cell Renal Cell Carcinoma Clinically Benefiting from First-Line Treatment with Ipilimumab Plus Nivolumab

Tripathi,

Meza,

Sayegh

et al. 2023

KCA

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Background: Ipilimumab plus nivolumab is approved as a first-line treatment for intermediate or poor risk metastatic renal cell carcinoma (mRCC). However, ∼35% of patients progress within six months on ipilimumab plus nivolumab, and no validated genomic biomarkers predict the benefit. In this study, we explore the genomic and transcriptomic differences among patients with clear cell mRCC patients who either did or did not experience clinical benefit from first-line ipilimumab plus nivolumab therapy. Method: Patients with clear cell mRCC intermediate or poor IMDC risk scores, with available tumor whole exome with/without transcriptome sequencing before starting systemic therapy were included. Patients who developed a complete response, partial response, or stable disease for at least six months after initiating treatment were categorized into the ‘clinical benefit’ group, whereas the rest were classified as ‘no clinical benefit.’ Genomic alteration frequencies between the groups were assessed with a chi-square test. Differentially expressed genes and gene sets were identified via DeSeq2 and GSEA v4.2.3, respectively. Result: 53 patients with clear cell mRCC (37 clinical benefit and 16 no clinical benefit) were eligible and included. No significant difference was found in the genomic alteration frequencies between these groups. Baseline tumor transcriptomic data were available for 14 patients (9 clinical benefit and 5 no clinical benefit). The apical surface and pathways downregulated by KRAS signaling were enriched in the clinical benefit group, whereas inflammatory pathways were enriched in the no clinical benefit group. Conclusion: These findings suggest that tumor specific gene expression as assessed by RNA sequencing could serve as a potential biomarker of response to ipilimumab plus nivolumab therapy.

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Section: Discussionmentioning

confidence: 99%

Genomic and Transcriptomic Characteristics of Tumors of Patients with Metastatic Clear Cell Renal Cell Carcinoma Clinically Benefiting from First-Line Treatment with Ipilimumab Plus Nivolumab

Tripathi,

Meza,

Sayegh

et al. 2023

KCA

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“…Nonetheless, some patients experienced resistance during or after treatment, leading to immune escape and tumor recurrence. Dual checkpoint blockade, which have synergistic anti-tumor effects in advanced malignancies, such as anti-CTLA-4 and anti-PD-1, could potentially serve as a more effective therapeutic strategy ( 23 ). Furthermore, recent studies have explored innovative strategies, such as bispecific antibodies targeting TGF-β and PD-L1 (BiTP), which have demonstrated potent antitumor activity in TNBC.…”

Section: Discussionmentioning

confidence: 99%

Single-cell and bulk RNA sequencing analysis of B cell marker genes in TNBC TME landscape and immunotherapy

Zhao,

et al. 2023

Front. Immunol.

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ObjectiveThis study amied to investigate the prognostic characteristics of triple negative breast cancer (TNBC) patients by analyzing B cell marker genes based on single-cell and bulk RNA sequencing.MethodsUtilizing single-cell sequencing data from TNBC patients, we examined tumor-associated B cell marker genes. Transcriptomic data from The Cancer Genome Atlas (TCGA) database were used as the foundation for predictive modeling. Independent validation set was conducted using the GSE58812 dataset. Immune cell infiltration into the tumor was assessed through various, including XCELL, TIMER, QUANTISEQ, CIBERSORT, CIBERSORT-ABS, and ssGSEA. The TIDE score was utilized to predict immunotherapy outcomes. Additional investigations were conducted on the immune checkpoint blockade gene, tumor mutational load, and the GSEA enrichment analysis.ResultsOur analysis encompassed 22,106 cells and 20,556 genes in cancerous tissue samples from four TNBC patients, resulting in the identification of 116 B cell marker genes. A B cell marker gene score (BCMG score) involving nine B cell marker genes (ZBP1, SEL1L3, CCND2, TNFRSF13C, HSPA6, PLPP5, CXCR4, GZMB, and CCDC50) was developed using TCGA transcriptomic data, revealing statistically significant differences in survival analysis (P<0.05). Functional analysis demonstrated that marker genes were predominantly associated with immune-related pathways. Notably, substantial differences between the higher and lower- BCMG score groups were observed in terms of immune cell infiltration, immune cell activity, tumor mutational burden, TIDE score, and the expression of immune checkpoint blockade genes.ConclusionThis study has established a robust model based on B-cell marker genes in TNBC, which holds significant potential for predicting prognosis and response to immunotherapy in TNBC patients.

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“…Treatment beyond progression is well defined in the therapy of NSCLC with specific agents such as tyrosine kinase inhibitors in special situations [ 24 , 25 ], but it is still not completely understood in treatment with IO [ 26 ]. The resistance mechanisms for this particular nivolumab plus ipilimumab combination are still not understood and may involve different pathways for IO, such as tumor microenvironment (TME) [ 27 ], as well as for chemotherapy, such as adaptive resistance mechanisms [ 28 ]. Taking these complex resistance mechanisms into account is important for routine clinical management in order to identify disease progression in a timely fashion and to switch to the next available treatment line before the cancer cells progress and become more resistant.…”

Section: Discussionmentioning

confidence: 99%

Multi-Center Real-World Outcomes of Nivolumab Plus Ipilimumab and Chemotherapy in Patients with Metastatic Non-Small-Cell Lung Cancer

Shalata,

Yakobson,

Dudnik

et al. 2023

Biomedicines

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Immune checkpoint inhibitors have become the standard of care in the treatment of metastatic non-small-cell lung cancer (NSCLC). The combination of nivolumab plus ipilimumab and chemotherapy has been shown to improve outcomes in terms of overall survival (OS) and progression-free survival (PFS). The aim of this study was to evaluate the outcomes of metastatic NSCLC treated in routine practice on the treatment regimen of the CheckMate 9LA protocol. Medical records of 58 patients treated at Soroka and Bnai Zion Medical Centers between May 2020 and February 2022 were analyzed. All patients were treated with a regimen of platinum-based chemotherapy combined with immunotherapy of nivolumab every three weeks and ipilimumab every 6 weeks. The patients received 2–3 cycles of chemotherapy according to the physician’s choice: platinum-based cisplatin or carboplatin with either pemetrexed or paclitaxel. The median PFS was 10.2 months, longer than that of the 9LA trial (6.7 months). Adenocarcinoma patients exhibited a higher median OS of 13.7 (range 5–33) months than squamous cell carcinoma (SCC) patients at 12.3 (5–20) months and PFS of 10.3 (4–33) months, while squamous cell carcinoma patients had a PFS of 9.2 (4–18) months. Patients whose programmed death ligand-1 (PD-L1) tumor expression level was ≥1% showed a higher median OS than those with PD-L1 expression of less than 1%. Treatment-related adverse events (TRAEs) were reported in 93.1% of patients, mostly grade 1 in severity. The first-line treatment of metastatic NSCLC patients in combination with nivolumab plus ipilimumab and chemotherapy can be given safely in routine clinical practice, with results comparable to those achieved in clinical trials of the regimen.

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Nivolumab plus ipilimumab combination therapy in cancer: Current evidence to date

Cited by 11 publications

References 203 publications

Genomic and Transcriptomic Characteristics of Tumors of Patients with Metastatic Clear Cell Renal Cell Carcinoma Clinically Benefiting from First-Line Treatment with Ipilimumab Plus Nivolumab

Genomic and Transcriptomic Characteristics of Tumors of Patients with Metastatic Clear Cell Renal Cell Carcinoma Clinically Benefiting from First-Line Treatment with Ipilimumab Plus Nivolumab

Single-cell and bulk RNA sequencing analysis of B cell marker genes in TNBC TME landscape and immunotherapy

Multi-Center Real-World Outcomes of Nivolumab Plus Ipilimumab and Chemotherapy in Patients with Metastatic Non-Small-Cell Lung Cancer

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