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Impact of aging on immune-related adverse events generated by anti-programmed death (ligand)PD-(L)1 therapies
Capucine Baldini1, Patricia Martin Romano1, Anne-Laure Voisin2
1Gustave Roussy, Université Paris-Saclay, Département d'Innovation Thérapeutique et d'Essais Précoces (DITEP), Villejuif, France.
Background:
Aging is an important risk factor for cancers and is associated with poor prognosis. Weakness of the immune system, also called immunosenescence may occur with older age. The impact of aging on efficacy and safety of immune checkpoint blockers, such as anti-programmed death (ligand) PD-(L)1, remains undetermined. This study aims to evaluate the incidence of immune-related adverse events (irAEs) in patients aged 70 years or older than their younger counterparts.
Methods:
Patients with advanced solid tumors treated at Gustave Roussy with an anti-PD-(L)1 monotherapy between June 2014 and October 2017 were prospectively included within the dedicated irAEs pharmacovigilance registry REISAMIC (Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie). The incidence of irAEs of grade ≥II was compared between patients aged ≥70 (old patients, OP) versus patients aged < 70 years (young patients, YP) using a chi-squared test. Survivals were estimated using the Kaplan-Meier method.
Results:
Among the 603 patients treated by anti-PD(L)1, 191 were ≥70 y.o (OP) and 424 < 70 y.o (YP). The median (range) age of OP and YP were respectively 77 (70-93) and 59 years old (17-69). A total of 165 irAEs occurred in these patients (103 grade II and 58 grade III-IV). The overall incidence of grade ≥II irAEs was higher in OP than in YP (33% versus 25%, p = 0.03). In addition, OP were more prone of having multiples irAEs compared with YP (p = 0.037). Skin toxicities were more frequent in OP than in YP (p = 0.007) but endocrine toxicities were less frequent in OP than in YP (p = 0.044). This higher level of irAEs seems to be responsible for a higher rate of treatment discontinuation in OP (p = 0.2). There was no statistical difference in median time to toxicity, exposure to steroids or survival between the two groups.
Conclusion:
Although anti-PD-(L)1 immunotherapies remain an acceptable treatment option for older patients, prescribers should be aware that irAEs are more frequent in the elderly. Further translational studies are warranted to better understand the relationship between aging and irAEs.
Insights
Older patients (≥70 years) experienced more frequent immune-related adverse events (irAEs) when treated with anti-programmed death (ligand) PD-(L)1 therapies. While generally safe, elderly individuals require careful monitoring for these toxicities.
Area of Science:
- Oncology
- Immunology
- Geriatrics
Background:
- Aging is a significant risk factor for cancer and is linked to poorer outcomes.
- Immunosenescence, or the decline of immune function with age, is a known phenomenon.
- The impact of aging on the efficacy and safety of immune checkpoint inhibitors (ICIs) like anti-PD-(L)1 therapies is not fully understood.
Purpose of the Study:
- To investigate the incidence of immune-related adverse events (irAEs) in elderly patients (≥70 years) compared to younger patients receiving anti-PD-(L)1 monotherapy.
- To assess the safety and tolerability of anti-PD-(L)1 therapies in older adults.
Main Methods:
- A prospective study included patients with advanced solid tumors treated with anti-PD-(L)1 monotherapy.
- The incidence of grade ≥II irAEs was compared between patients aged ≥70 years (old patients, OP) and those <70 years (young patients, YP) using a chi-squared test.
- Survival outcomes were analyzed using the Kaplan-Meier method.
Main Results:
- The overall incidence of grade ≥II irAEs was significantly higher in OP (33%) compared to YP (25%).
- OP were more likely to experience multiple irAEs and skin toxicities, while endocrine toxicities were less frequent.
- Treatment discontinuation due to irAEs was higher in OP, though not statistically significant.
Conclusions:
- Anti-PD-(L)1 immunotherapies are an acceptable treatment option for elderly cancer patients.
- Prescribers must be aware of the increased frequency of irAEs in older individuals.
- Further research is needed to elucidate the relationship between aging and irAEs.
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