Immune checkpoint inhibitors therapy in older patients (≥ 70 years) with metastatic melanoma: a multicentre study

Cybulska-Stopa, Bożena; Ługowska, Iwona; Jagodzińska-Mucha, Paulina; Koseła-Paterczyk, Hanna; Kozak, Katarzyna; Klimczak, Anna; Świtaj, Tomasz; Ziobro, Marek; Roman, A Santiuste; Rajczykowski, Marcin; Suwiński, Rafał; Niemiec, Maciej; Zemełka, Tomasz; Falkowski, Sławomir; Rutkowski, Piotr

doi:10.5114/ada.2018.79940

Cited by 15 publications

(12 citation statements)

References 20 publications

(22 reference statements)

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“…Various immune checkpoint inhibitor anticancer drugs targeting the PD-1/PD-L1 checkpoint have been approved for clinical use in some cancers, including metastatic melanoma, non-small-cell lung carcinoma (NSCLC), renal cell carcinoma, and UC. Additionally, there are ongoing clinical trials in other solid tumors and hematological cancers [15,16,17].…”

Section: Discussionmentioning

confidence: 99%

Programmed cell death protein 1 and programmed death ligand 1 expression in neuroendocrine carcinomas of the urinary bladder

Acikalin¹,

Bağır²,

Inceman³

et al. 2020

pjp

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Neuroendocrine carcinomas (NECs) of the urinary bladder are rare and aggressive, without an effective treatment approach. Immune checkpoint inhibitor agents targeting the interaction of programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) have been approved for urothelial carcinoma, but their use for small-cell carcinoma (SmCC) of the urinary bladder is unclear. Thus, we analyzed PD-1 and PD-L1 expression in NECs, particularly in SmCC of the urinary bladder. We used PD-1 antibody and two different biomarkers for PD-L1 antibodies, Ventana SP263 (Ventana Medical Systems, Inc.) and AM26531AF-N (Acris Antibodies GmbH). Among the 12 SmCC cases, 16.7% stained positive on immune cells for PD-1 and 33.0% for PD-L1. PD-L1 positivity on tumor cells was 25.0% of SmCC cases. The overall survival was shorter in PD-L1-positive patients compared with PD-L1-negative patients (15.4 months vs. 27.6 months). Large cell carcinoma (n = 1) was strongly and diffusely stained with PD-L1, and this case had the longest survival (68 months) in the group. Immune checkpoint inhibitors may be an alternative treatment option in SmCC of the urinary bladder. Furthermore, the absence of PD-L1 may be a good prognostic parameter.

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Section: Discussionmentioning

confidence: 99%

Programmed cell death protein 1 and programmed death ligand 1 expression in neuroendocrine carcinomas of the urinary bladder

Acikalin¹,

Bağır²,

Inceman³

et al. 2020

pjp

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“…Also our analyses confirmed that the survival and toxicity profile in the older patients (≥ 70 years) treated with immune checkpoint inhibitors including nivolumab are similar to younger patients (< 70 years). In fact even the presence of co-morbidities may not associated with an increased risk of immunotherapy toxicity (p = 0.790) [67]. Recently published data are also indicating that patients age ≥70 with indirect frailty markers such as having fallen in the prior six months, ECOG PS ≥2 or Charlson comorbidity scores ≥11 experience similar rates of immunotherapy toxicity [68].…”

Section: Safety Of Nivolumab In Challenging Subgroups Of Patientsmentioning

confidence: 99%

An update on the safety of nivolumab for the treatment of advanced melanoma

Czarnecka

Rutkowski

2020

Expert Opinion on Drug Safety

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Introduction: Due to its unique mechanism of action as an immune checkpoint inhibitor, nivolumab has high antitumor activity, but at the same time this mechanism is responsible for immune-related adverse events that may limit patients' safety and therapy continuation. Areas covered: Long-term safety of nivolumab including 5-year follow-up, safety of nivolumab treatment after ipilimumab therapy, safety of nivolumab in challenging subgroups (elderly, patients with brain metastases, patients with autoimmune disorders), safety of nivolumab in with rare melanoma subtypes (including mucosal melanoma), as well as specificity of AEs reported for nivolumab treatment in melanoma patients in comparison to other cancer types and other immunotherapy molecules, and impact of AEs on response rates and PFS on nivolumab treatment are discussed. Expert opinion: Search for biomarkers that would help us to identify patient populations that may suffer from severe nivolumab toxicity could help in selecting patients that should not be treated with this type of therapy. Novel combinations and immunotherapy drugs including use of NKTR-214 (IL-2 pathway), lymphocyte-activation gene 3 (LAG-3), local injections of talimogene laherparepvec (T-VEC), or systemic use of T-cell receptors agonists such as OX40, CD137, ICOS-1, could provide regimens with limited toxicity and higher activity.

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“…For example, Sun et al revealed that there was no significant difference in the OS of patients with NSCLC using PD-1/PD-L1 inhibitors between the young group (< 65 years old) and the old group (≥65 years old) (12). At the cutoff point of 70 years old, the PFS and OS of patients treated with ICIs in the melanoma, NSCLC and pan-cancer datasets were similar (13)(14)(15). Another analysis of renal cell carcinoma (RCC) and urothelial carcinoma (UC) as a whole or in subgroups showed that older patients over 75 years old had disease control rates (DCRs) comparable to those of younger patients treated with ICIs (16).…”

Section: Introductionmentioning

confidence: 99%

Influence of Different Age Cutoff Points on the Prediction of Prognosis of Cancer Patients Receiving ICIs and Potential Mechanistic Exploration

et al. 2021

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Age is a potential predictive marker for the prognosis of cancer patients treated with immune checkpoint inhibitors (ICIs), but the appropriate age cutoff point is still controversial. We aimed to explore the influence of different age cutoff points on the prediction of prognosis for patients receiving ICIs and explore the mechanism underlying the appropriate age cutoff point from the aspects of gene mutation and expression, immune cell infiltration and so on. We applied cutoff points of 50, 55, 60, 65, 70, and 75 years old to divide 1660 patients from the Memorial Sloan-Kettering Cancer Center (MSKCC) immunotherapy cohort into older and younger groups and performed survival analysis of the six subgroups. The results showed that older patients had better survival than younger patients in accordance with the cutoff point of 50 years old [median overall survival (OS) (95% CI): 13.0 (10.5-15.5) months vs. 20.0 (16.7-23.3) months; p=0.002; unadjusted hazard ratio (HR) (95% CI): 0.77 (0.65-0.91)], whereas no significant difference was observed with other cutoff points. Further analysis of The Cancer Genome Atlas (TCGA) database and the MSKCC immunotherapy cohort data showed that the tumor mutation burden (TMB), neoantigen load (NAL), DNA damage response and repair (DDR) pathway mutation status, mutation frequencies of most genes (except IDH1, BRAF and ATRX), the expression of most immune-related genes and the degree of infiltration of most immune cells (such as CD8+ T cells and M1 macrophages) were higher in the elderly group (aged ≥50 years).

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Immune checkpoint inhibitors therapy in older patients (≥ 70 years) with metastatic melanoma: a multicentre study

Cited by 15 publications

References 20 publications

Programmed cell death protein 1 and programmed death ligand 1 expression in neuroendocrine carcinomas of the urinary bladder

Programmed cell death protein 1 and programmed death ligand 1 expression in neuroendocrine carcinomas of the urinary bladder

An update on the safety of nivolumab for the treatment of advanced melanoma

Influence of Different Age Cutoff Points on the Prediction of Prognosis of Cancer Patients Receiving ICIs and Potential Mechanistic Exploration

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