Rheumatic immune adverse effects posing challenges for oncology patients

There are still more questions than answers about rheumatic immune-related adverse events (irAEs) associated with anti-programmed death 1 (PD-1) cancer therapies.

However an Australian case series of 36 cancer patients with either rheumatic disease preceding their immunotherapy or who developed de novo rheumatic irAEs after treatment has shed some more light on their presentation, management and impact.

It adds to patient experiences from other Australian and European case series reported earlier this year in the limbic.

The recent Melbourne study found 10 of the 12 patients with pre-existing rheumatic conditions experienced flares after anti-PD1 treatment.

Flares described as immune arthritis typically occurred at about six weeks while polymyalgia rheumatica occurred at about 18 weeks.

All flares required corticosteroid treatment for at least six months and half the patients also required DMARDs.

In patients who developed de novo rheumatic irAEs, most (75%) were described as immune arthritis and typically presented at 18.5 weeks.

Myositis, polymyalgia rheumatic and fasciitis were also described with a short median time of 3.3 weeks from anti-PD1 treatment to the onset of myositis.

All cases were seronegative for rheumatoid factor and anti-citrullinated peptide antibody.

Corticosteroid treatment was required for symptom control in 78% of patients with some also requiring DMARDs and most requiring treatment for at least six months.

“In our cohort, all 34 rheumatic irAEs improved with intervention. However, most patients’ symptoms did not resolve. Twenty-five improved with immunomodulators alone, four with rheumatologic treatment plus discontinuation of immune checkpoint inhibitors (ICI), three with discontinuation of ICI and two with analgesia alone,” the study authors said.

Co-author of the paper Dr Shahneen Sandhu told the limbic the impact of rheumatic irAEs and the antirheumatic drugs used to manage them was still not well understood.

She said the current evidence was limited and there was a need for the many questions about PD1 inhibitors and rheumatic irAEs to be addressed in a prospective and systematic way.

“How do we know every patient requires two years of treatment or ad infinitum? We don’t know that. The reality is that a subset of these patients who get some of these side effects have probably got a primed immune system to start off with and maybe don’t need that extended duration of treatment.”

“Is throwing immunosuppressants into the mix a good idea? I personally don’t think so because you dampen down the immune system, but at the same time we are really needing to learn more about how these patients do in the long term and what some of the immunosuppression do in the long term as well.”

Dr Sandhu, from the Peter MacCallum Cancer Centre and Austin Health, said rheumatic irAEs were probably more frequent than previously expected but oncologists were having to learn to manage them.

“These symptoms impact quality of life. Early on I used to say to my patients with arthralgia, let’s push on with the treatment and minimise the steroids or anti-inflammatories. Then one of my patients essentially said they felt so bad they might commit suicide. So then you realise – something that you think is not burdensome to the patients even grade 1 or grade 2 irAEs, can have a huge impact on someone’s function.”

“So we do need to learn how to manage these side effects better and it may well be that if you’ve find somebody has had an excellent response, maybe you stop the treatment rather than throwing in immunosuppression when you have no clue whether it is going to have a detrimental effect on the cancer.”

The study found PET/CT scans frequently identified an inflammatory process that was more widespread than expected.

“For example, a patient might come in complaining of some joint tenderness so then you do a PET scan and find the muscles of the spine are also inflamed,” she said.

However she did not think the cost of routine PET/CT scans was worthwhile and instead should be reserved for cases where a diagnosis was particularly challenging.

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