Immunotherapy in older patients with cancer

Abstract

Ageing implicates a remodeling of our immune system, which is a consequence of the physiological senescence of our cells and tissues coupled with environmental factors and chronic antigen exposure. An immune system that senesces includes more differentiated cells with accumulation of highly differentiated CD4 and CD8 T cells. The pool of naive T cells decreases with the exponential thymic involution induced by age. Differentiated T cells have similar, if not higher, functional capacities but scarce studies are looking at the impact of senescence among specific T cells. After a stimulation, other immune cells (monocytes, dendritic cells and NK) are functionally altered during ageing. It is as if the immune system was more efficient at the basal level, but less efficient after a stimulation in the old compared to young people, likely due to less reserve. Concerning the clinical impact, older people are more prone to certain pathogens and their clinical manifestations differ from the younger people. Severe flu and VZV reactivation are more frequent with an altered cellular response to vaccination. Vaccination failure can have detrimental consequences in people presenting frailty criteria. Old people frailty is majored by their comorbidities and diseases like cancer. Thus, chemotherapies are employed with circumspection in older patients. The use of anti-PD-1/PD-L1 immunotherapies is therefore attractive, because of less side effects with a better response compared to chemotherapy. Old persons inclusion is lacking in current studies and clinical trials. Some subgroups or pooled analyses confirm the gain in response without increased toxicities in older patients but their inclusion criteria differ from the real-life practice. Specific studies focusing on this population are needed because of the increasing cancer incidence with age and the overall ageing of the population.

Overcoming Resistance to Immunotherapy in Advanced Cutaneous Squamous Cell Carcinoma

“…However, in patients older than 75 years, resistance to anti-PD-1/anti-PD-L1 therapy has been observed in squamous cell carcinoma and adenocarcinoma of the lung, renal cell carcinoma and squamous cell carcinoma of the digestive tract. Nevertheless, two other studies in NSCLC reported the same benefit in the elderly as that seen in younger individuals [99,100].…”

Efficacy and toxicity of weekly paclitaxel, carboplatin, and cetuximab as induction chemotherapy or in cases of metastases or relapse for head and neck cancer with a focus on elderly or frail patients

“…The KEYNOTE‐048 trial 7 established pembrolizumab, with or without a chemotherapy backbone, as the new standard of care for metastatic or recurrent head and neck cancer. While there is a dearth of studies specifically for the elderly and frail population, immunotherapy is often considered a good option for this subgroup given its efficacy and lower rate of toxicities 47 . The KEYNOTE trial was published in 2019, after most of the patients in this study received PCC, which is reflected in the fact that only 6 patients out of 80 received immunotherapy prior to PCC, although 26 patients received subsequent immunotherapy.…”

Management of Elderly and Old Cancer Patients – Geriatric Oncology

“…32 Treatment with anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) agents is, therefore, an attractive option for elderly patients with multiple comorbidities. 33 Pooled data on elderly patients (aged 75 years and above) with PD-L1-positive advanced nonsmall-cell lung cancer (NSCLC) from three landmark cancer trials were recently analyzed. 34 Results demonstrated that immunotherapy improved overall survival in these patients compared with chemotherapy, and results were comparable to the overall population results in the individual studies.…”