Medicines

Study profiles hospital admissions due to irAEs with checkpoint inhibitors


About one in ten patients treated with immune checkpoint inhibitors require hospitalisation for immune-related adverse events (irAE), a study from Queensland has found.

A retrospective analysis of record for 140 patients with solid cancer treated with checkpoint inhibitors at the Royal Brisbane and Women’s Hospital and The Prince Charles Hospital in 2016 and 2017 found that 15 patients (11% of the overall cohort) had 18 hospital admissions attributable to irAE.

The patients were being treated with checkpoint inhibitors for conditions such as non-small cell lung cancer (41%) and melanoma (18%), and most common checkpoint inhibitor treatments were anti-PD1 therapy (78%) and anti-PD-L1 (19%).

The most common irAE requiring admission was pneumonitis (6), followed by hepatitis (3), colitis (3), and one each of nephritis, peripheral motor neuropathy, arthritis, and rash.

All patients received high-dose corticosteroids and two thirds (66%) of the irAE s resolved completely with no long-term complications. However there were some serious long term complications such as unnresolved toxicity, long-term organ damage and one irAE-related death. This occurred in a patient with lung cancer who had pneumonitis and developed multifactorial respiratory failure including exacerbation of advanced emphysema.

Overall, however, a hospital admission for irAE did not significantly impair overall survival, in contrast to admissions for other reasons such as intercurrent illness or malignancy-related complications.

Of the 15 patients with an irAE admission, immune oncology therapy was discontinued in 10, and four of the five others had successful re-challenge.

The study authors noted that in almost 40% of the admissions irAE was not considered as the differential diagnosis at presentation and this led to a delay in starting corticosteroids (2.7 vs 1.2 days) but was not associated with worse outcomes.

Patients admitted for irAE had a significantly longer duration on immune checkpoint inhibitors compared to patients admitted for other reasons (173 vs 105 days) but the lengths of hospital stay were similar (9.0 vs 8.5 days).

The relatively high rate of irAE as a missed differential diagnosis on admission suggests a need for improved cross-discipline awareness, education, and institutional management guidelines.

The study investigators said the findings also highlighted the need for multidisciplinary involvement in detection and avoidance of irAE, as in the case of a patient who developed a perforated bowel due to ICI-induced colitis which was related to nonadherence to treatment and late presentation.

Comorbidities, such as premorbid lung disease, in combination with  an irAE could also result in poor outcomes, they said.

“Care of patients with high-grade irAE frequently warrants expertise from other subspecialties, and demonstrates a need for ongoing education for oncologists and nononcologists alike in the management of unique immune toxicities,” they concluded.

The findings are published in the Asia Pacific Journal of Oncology.

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