Management of immune checkpoint inhibitor-associated toxicities in older adults with cancer: recommendations from the International Society of Geriatric Oncology (SIOG)
Summary
Immune checkpoint inhibitors (ICIs) have substantially advanced the treatment landscape for a wide variety of malignancies. Older adults represent a large and rapidly growing demographic, among whom ICIs are widely prescribed. Management of ICI-associated toxicity among older adults, particularly in the presence of frailty and comorbidity, poses unique challenges. In this Policy Review, developed by the International Society of Geriatric Oncology (SIOG), we offer an evidence-based framework for health-care providers, caregivers, and policy makers for treating older adults with ICIs, focusing on unique considerations for this population that are not adequately addressed by existing guidelines, and expanding them to encompass geriatric oncology principles.
Introduction
The introduction of immune checkpoint inhibitors (ICIs) has transformed cancer treatment, offering effective therapy that is often more tolerable for older patients relative to historical standards of care. Older patients (defined broadly as adults aged ≥70 years) represent a large and growing proportion of patients seen in oncological practice, and frequently present with substantial comorbidity, frailty, and functional impairments.
Despite the therapeutic potential and advantages of ICIs, their use can expose patients to immune-related adverse events, which, even at low grades, can substantially impact the wellbeing and health-related quality of life of older patients with underlying comorbidity or frailty. The management of immune-related adverse events frequently necessitates prolonged immunomodulatory and immunosuppressive therapy (>4 weeks), posing additional risks, particularly for older patients. These factors often complicate the management of low-grade toxicity and can have a disproportionate impact on older patients’ quality of life and ability to continue treatment.1, 2, 3
Major immunotherapy guidelines (eg, the American Society of Clinical Oncology,4 the National Comprehensive Cancer Network,5 the European Society of Medical Oncology,6 and the Society of Immunotherapy of Cancer7) offer detailed evidence-based guidance for managing individual immune-related adverse events, organised by organ system, and focusing primarily on pharmacotherapy. In general, the principles of these guidelines apply equally to older patients. Nonetheless, despite the utility of such guidelines, organ-based approaches are not always suitable to address the specific needs of older populations.
This Policy Review addresses unique aspects in the management of ICI-associated (eg, anti-PD-1 or anti-PD-L1 [anti-PD(L)-1], and anti-CTLA-4) toxicities among older adults, defined broadly here as adults 70 years and older, in line with previous guidelines from the International Society of Geriatric Oncology (SIOG) and expert consensus. In this Policy Review, we highlight considerations for the management of the most prevalent immune-related adverse events among older patients and the use of immunosuppressive agents in this population. Additionally, we offer guidance regarding the use of comprehensive geriatric assessment (CGA) as a tool to contextualise toxicity in relation to patient-centred care among older patients, whose treatment priorities often favour quality of life and functional independence over survival alone.
https://www.sciencedirect.com/science/article/abs/pii/S1470204524004042