Patients treated with immune checkpoint inhibitors may develop severe immune-related adverse events (irAEs) months or even years after starting therapy, a new study shows.
US researchers say vigilance is needed for late-onset irAEs because at least one in ten of them occur more than a year after initial exposure to immunotherapy.
The findings come from a review of records for 795 cancer patients who were hospitalised at the Massachusetts General Hospital for irAEs following treatment with anti-PD-1 and anti-PD-L1 monotherapy for condition such as melanoma and lung cancer.
Most irAEs occurred early, within six months of starting therapy, with a median time to hospitalisation for irAE of 2.7 months, the study investigators reported in JAMA Network Open (link here).
However, almost 15% of patients (n = 117) presented with irAE six to 12 months after initial checkpoint inhibitor exposure and 11% of patients (86) more than a year after initial exposure.
Late-onset irAEs were more likely to involve the kidney (31%) and haematologic (22%) organ systems or be rheumatologic (15%), whereas early onset irAEs tended to affect the GI system (26%) and lungs (14%).
Patients with lung, genitourinary, and gynaecologic cancers were the most likely to have late-onset irAEs.
The type of checkpoint inhibitor influenced the timing of hospital admission for irAEs; with 13.5% of patients receiving anti–PD-L1–based therapy presenting late compared with 5.4% of those receiving therapy with anti–CTLA4 agents.
Patients receiving immunotherapy in the perioperative setting were significantly more likely to be admitted at the intermediate interval (23.5%) compared with those with metastatic disease (12.8%).
However there was no link between common demographic factors, including sex and prior exposure to an ICI, and late-onset irAEs.
Active exposure to checkpoint inhibitor therapy was also significantly associated with the timing of irAE: among the patients presenting late, 7.4% had received recent ICI therapy (within the last 60 days) compared with 26.4% who had not had recent exposure.
The study investigators said the underlying mechanism for late-onset irAEs was unclear, and further work was needed to better characterise the potential associations between these patient populations and the reatments they received with the risk of late-occurring irAEs.
Potential hypotheses for mechanisms of late-occurring irAEs include heterogeneity in the tumour microenvironment and variable duration of checkpoint inhibitor therapy, they said, as well as exposure to subsequent therapies, such as targeted therapies, that may increase the risk of the development of irAEs.
“Clinicians must remain vigilant for irAEs regardless of elapsed time from ICI therapy, especially as patients live longer and ICIs become more widely used,” they advised.