Medicines

Nuance needed with steroids for checkpoint inhibitor side-effects


A more individualised approach is needed in the use of corticosteroids for immune checkpoint inhibitor side-effects, according to oncologists who recommend lower initial ‘test’ doses and shorter durations to avoid additional complications.

With immune related adverse events (irAE) occurring in between 15% and 55% of patients taking PD-1 inhibitors and CTLA-4 antibodies, the use of corticosteroids for immunosuppression is becoming widespread, they note in a paper published in The Lancet Oncology (link).

But the use of steroids needs to be balanced against their own risks of increasing infection, as well as bone, muscle, metabolic, cardiovascular and neuropsychiatric toxicity, according to the authors, including Dr Lavinia Spain, a medical oncologist at the Peter Mac Cancer Centre, Melbourne.

Current use of corticosteroids for irAE is guided by historical trial data and expert opinion, rather than prospective studies to ascertain the optimum dose and duration, they observe.

However the ‘blunt tool’ criteria used for checkpoint inhibitor adverse effects may be encouraging a suboptimal ‘one size fits all’ approach that leads to corticosteroids being overused, they suggest.

For example, while neurological and cardiac side-effects need to be taken extremely seriously, the same might not be true for endocrine, skin, gastrointestinal, renal, and hepatic side-effects when it comes to withholding immune checkpoint inhibitor therapy and initiation of immunosuppression.

Consideration is also needed of the rate of change of side-effects over time (the ‘tempo’) as some may plateau after they first occur while others may worsen daily or respond differently to corticosteroids.

“In our experience, tempo of side-effects can be extremely useful in deciding when to start and subsequently increase or reduce immunosuppression,” they write.

To address these issues they suggest the use of a lower test dose of corticosteroid initially, such as 0·5 mg/kg prednisolone, which should be reviewed after 24 or 48 hours and adjusted as necessary on the basis of the effect of immunosuppression on the tempo and severity of the side-effect.

“In terms of finding a sweet spot, the key principle is that the minimum safe level of immunosuppression should be initiated, taking into account the type of side-effect, severity, tempo, and patient compliance,” the authors say.

However, while currently used initial doses of corticosteroid may be considered too high, the minimum safe dose will need to be determined for each immune-related adverse event individually.

“Importantly, the concept of a test dose is only suitable for immune-related adverse events that are not potentially fatal in their early phase, that evolve over a longer time, and that can be monitored easily (eg, hepatitis or colitis),” they say.

Meanwhile, with up to half of cancer patients being potentially eligible for checkpoint inhibitor treatment, there is a need for prospective trials to determine the minimum safe dose thresholds for corticosteroids for different adverse events, they conclude.

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