Immune Checkpoint Inhibitors: The Unexplored Landscape of Geriatric Oncology

Choucair, Khalil; Naqash, Abdul Rafeh; Nebhan, Caroline A.; Nipp, Ryan David; Johnson, Douglas B.; Saeed, Anwaar

doi:10.1093/oncolo/oyac119

Cited by 3 publications

(3 citation statements)

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“…Although elderly (≥65 years old) patients consist of over 50% of cancer patients, they are underrepresented in the clinical trials leading to the FDA approval of ICI trials. Currently data suggest age does not significantly affect the tolerability and clinical response to ICI monotherapy ( 47 ). However, aging is associated with “immunosenescence”, which includes dysregulation of both cellular and humoral immunity; and is associated with lymphocyte depletion, fewer CD4+ and CD8+ T cells, decreased diversity of regulatory and memory T cells, defective DNA repair response pathway, and metabolic changes.…”

Section: Discussionmentioning

confidence: 99%

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Hospitalized cancer patients with comorbidities and low lymphocyte counts had poor clinical outcomes to immune checkpoint inhibitors

Young

Panchal

et al. 2022

Front. Oncol.

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BackgroundImmune checkpoint inhibitor (ICI) therapy has improved survivals with a favorable toxicity profile in a variety of cancer patients. We hypothesized that hospitalized cancer patients who have acute or chronic comorbidities may have suppressed immune systems and poor clinical outcomes to ICIs. The objective of this study was to explore clinical outcomes and predictive factors of hospitalized cancer patients who received ICI therapy at an NCI-designated Comprehensive Cancer Center.MethodsA retrospective review of electronic medical records was conducted for adult cancer patients who received an FDA-approved ICI during admission from 08/2016 to 01/2022. For each patient we extracted demographics, cancer histology, comorbidities, reasons for hospitalization, ICI administered, time from treatment to discharge, time from treatment to progression or death, and complete blood counts. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared using the log-rank test. The 95% confidence interval for survival was calculated using the exact binomial distribution. Statistical significance was defined as 2-sided p<0.05.ResultsOf 37 patients identified, 2 were excluded due to lack of complete blood counts on admission. Average hospital stay was 24.2 (95% CI 16.5, 31.9) days. Ten (27.0%) patients died during the same hospitalization as treatment. Of those who followed up, 22 (59.5%) died within 90 days of inpatient therapy. The median PFS was 0.86 (95% CI 0.43, 1.74) months and median OS was 1.55 (95% CI 0.76, 3.72) months. Patients with ≥3 comorbidities had poorer PFS (2.4 vs. 0.4 months; p=0.0029) and OS (5.5 vs. 0.6 months; p=0.0006). Pre-treatment absolute lymphocyte counts (ALC) <600 cells/µL were associated with poor PFS (0.33 vs. 1.35 months; p=0.0053) and poor OS (0.33 vs. 2.34 months; p=0.0236). Pre-treatment derived neutrophil to lymphocyte ratio (dNLR) <4 was associated with good median PFS (1.6 vs. 0.4 months; p=0.0157) and OS (2.8 vs. 0.9 months; p=0.0375).ConclusionsAdministration of ICI therapy was associated with poor clinical outcomes and high rates of both inpatient mortality and 90-day mortality after inpatient ICI therapy. The presence of ≥3 comorbidities, ALC <600/μL, or dNLR >4 in hospitalized patients was associated with poor survival outcomes.

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Section: Discussionmentioning

confidence: 99%

“…In addition, aging is associated with “inflammaging”, which has an overall increased pro-inflammatory state. All these factors were associated with decreased response to ICI therapy ( 47 ). In our study, the mean age was 53.5 years, and 13 (35%) of cancer patients were ≥65 years old.…”

Section: Discussionmentioning

confidence: 99%

Hospitalized cancer patients with comorbidities and low lymphocyte counts had poor clinical outcomes to immune checkpoint inhibitors

Young

Panchal

et al. 2022

Front. Oncol.

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“…Consequently, a comprehensive understanding of ICI tolerance and effects in the elderly remains elusive [ 29 , 30 , 31 ]. The age-related remodeling process of the immune system, termed immunosenescence, is hypothesized to impact the efficacy and toxicity of ICI in the geriatric oncology population [ 31 , 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy in Elderly Patients—Single-Center Experience

Ramos,

Mendes,

Romão

et al. 2023

Cancers

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Cancer management faces a substantial challenge posed by the aging demographic. Aging is marked by accumulated DNA damage, and this phenomenon is implicated in the process of tumorigenesis. The concept of immunosenescence, postulated to manifest in elderly individuals, is defined by an age-related decline in T cells and a simultaneous elevation in proinflammatory status, leading to a diminished efficacy in response to immunotherapy. Notably, despite the rising prevalence of cancer in the elderly population, their underrepresentation in clinical trials persists. This underscores the unmet need to evaluate the safety and efficacy of cancer treatment in the elderly. This retrospective, single-center cohort study aimed to assess and evaluate the effectiveness and safety of immunotherapy in patients compared to younger individuals with metastatic solid tumors receiving ICI. A total of 220 patients were included, mostly males, with a median age of 64. The proportion of patients ≥ 65 years old was 56.5%. The use of ICI showed no significant differences concerning overall survival (OS) and progression-free survival (PFS) among age groups across different cancer types (melanoma, non-small-cell lung cancer (NSCLC), renal, and bladder cancer; p = 0.388). Concerning the response to treatment in renal cancer patients, a significant difference was observed (p = 0.041), suggesting a potential negative impact of age on the treatment response. In patients that presented immune-related adverse events (irAEs), oral corticosteroid therapy was marginally associated (p = 0.059) with the elderly population. When evaluating the NSCLC population alone (n = 131, 59.5%), our study revealed a strong association between the development of irAEs, patients’ PFS and OS, and the duration of ICI treatment, but not directly correlated with age. The NSCLC elderly population presented a marginally greater number of irAEs, although without statistical significance (p = 0.86). ICI maintained efficacy and safety in elderly patients, challenging the notion that age alone should determine treatment decisions. The findings emphasize the necessity of a comprehensive geriatric assessment rather than relying solely on chronological age for personalized cancer treatment in the elderly population. Further prospective studies are needed to better understand immune responses in older adults and derive predictive biomarkers for cancer treatment.

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The Role of Aging and Senescence in Immune Checkpoint Inhibitor Response and Toxicity

Jain,

Burton Sojo,

Sun

et al. 2024

IJMS

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Cellular senescence accumulates with age and has been shown to impact numerous physiological and pathological processes, including immune function. The role of cellular senescence in cancer is multifaceted, but the impact on immune checkpoint inhibitor response and toxicity has not been fully evaluated. In this review, we evaluate the impact of cellular senescence in various biological compartments, including the tumor, the tumor microenvironment, and the immune system, on immune checkpoint inhibitor efficacy and toxicity. We provide an overview of the impact of cellular senescence in normal and pathological contexts and examine recent studies that have connected aging and cellular senescence to immune checkpoint inhibitor treatment in both the pre-clinical and clinical contexts. Overall, senescence plays a multi-faceted, context-specific role and has been shown to modulate immune-related adverse event incidence as well as immune checkpoint inhibitor response.

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Immune Checkpoint Inhibitors: The Unexplored Landscape of Geriatric Oncology

Cited by 3 publications

References 104 publications

Hospitalized cancer patients with comorbidities and low lymphocyte counts had poor clinical outcomes to immune checkpoint inhibitors

Hospitalized cancer patients with comorbidities and low lymphocyte counts had poor clinical outcomes to immune checkpoint inhibitors

Immunotherapy in Elderly Patients—Single-Center Experience

The Role of Aging and Senescence in Immune Checkpoint Inhibitor Response and Toxicity

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