Dr Postow on the Principles Guiding Long-Term Management of Chronic irAEs in Melanoma

“We call a lot of things permanent, but permanent in many of these clinical trials is just [based on] a few years of follow-up. We don’t really know what happens 10, 20, 30 years after discontinuing these drugs, so [we need] to try to learn as much as possible about what happens long-term.”

Michael A. Postow, MD, chief of the Melanoma Service at Memorial Sloan Kettering Cancer Center, discussed the long-term management of immune-related adverse effects (irAEs) following immune checkpoint inhibitor (ICI) therapy in melanoma.

Chronic management of irAEs remains an evolving area of clinical practice, with significant gaps in evidence that extend beyond the follow-up windows captured in pivotal trials, Postow explained. Many AEs historically categorized as “permanent” reflect only a few years of post-treatment observation. The long-term trajectory of these events 10, 20, or 30 years after ICI discontinuation is largely unknown, underscoring the need for prospective data collection in this patient population, Postow noted.

Certain irAEs are recognized to persist for extended periods. Endocrinopathies including hypothyroidism and adrenal insufficiency secondary to immune-mediated hypophysitis typically necessitate lifelong hormonal replacement under endocrinology co-management, Postow said. Consistent laboratory monitoring and patient-reported symptom tracking are essential components of follow-up for these individuals, who carry what amounts to a new chronic medical condition. Musculoskeletal toxicities, including immune-mediated arthralgias, represent another common lingering irAE. Management may require low-dose corticosteroids, hydroxychloroquine, or disease-modifying agents such as methotrexate, with rheumatology involvement indicated in refractory cases, Postow added.

However, optimal management strategies for chronic irAEs remain undefined. Even acute-phase management lacks robust evidence in many cases. As the population of patients living with chronic irAEs grows, clinical trial infrastructure to evaluate management strategies is increasingly warranted. Grant funders and academic organizations have identified this as a research priority, Postow underscored. Multidisciplinary coordination spanning oncology, endocrinology, and rheumatology, alongside rigorous longitudinal follow-up, will be critical to advancing evidence-based care for this expanding patient population, Postow concluded.