Reassurance on infection risk with checkpoint inhibitors

Rates of infection appear similar in patients with solid tumours before and after they receive immune checkpoint inhibitor (ICI) therapy.

A retrospective study from the Canberra Hospital assessed infection rates in 327 patients who commenced ICIs between 2012 and 2019. Patients were mainly being treated for metastatic disease in melanoma (47%) and NSCLC (36%) and anti-PD-1 antibodies were the most commonly used agents.

The chart review identified 535 culture or PCR-confirmed infections, mostly of the skin, respiratory and genitourinary systems. Most infections were bacterial such as S. aureus on the skin and E. coli or Klebsiella species UTIs.

The study, reported in Cancer Medicine, said the infection rates before ICI therapy commenced was 34% compared to 27% during or after ICI therapy.

Most post-ICI infections occurred in the first 12 months following the start of therapy with a median onset of 123 days.

“ICIs have relatively long half lives (pembrolizumab—22 days; nivolumab—25 days) and resultant immunomodulatory effects are expected to persist beyond the time of drug administration,” the study said.

“Furthermore, many immune-mediated adverse events have a delayed onset of months following ICI initiation; thus, the use of corticosteroids or other immunosuppressive for toxicity treatment, and secondary opportunistic infections can have delayed onset.”

The study, coauthored by Dr Yada Kanjanapan and Professor Desmond Yip, also found the site of infection and type of infectious organism were similar across the pre- and post-ICI periods.

“Diabetes and receipt of corticosteroids did not influence the infection risk, although this may be partially due to antimicrobial prophylaxis for opportunistic infections in patients requiring prolonged corticosteroid administration,” they said.

As well, there was no statistically significant impact on infection risk with the use of combination immunotherapy, such as anti-PD-1 plus anti-CTLA4 antibodies, compared to single-agent ICI.

The study found only older age >67 years was a risk factor for increased rate of infections post-ICI therapy.

Dr Kanjanapan told the limbic that whether or not immune checkpoint inhibitors increased the risk of infection was an important clinical question.

“Based on this study alone it is not possible to conclude about any specific measures for patients in the over 67 age group, in terms of reducing their risk of infection in this setting.”

“I think the next step, in terms of the next level of evidence, would be to really examine this more closely within the prospective ICI trials. Adverse events are captured but I think one challenge would be recognising these as potentially drug related events.”

She said it was reassuring that there was no signal for overwhelming worsening of infection risk or potential reactivation of infections such as TB.

Dr Kanjanapan said their findings – including that corticosteroid use did not seem to contribute to greater infection risk – had since been validated in a French study.

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