How Much Prednisone Is Too Much in Treating Rheum Effects From Cancer Therapies?

LONDON — Overall survival is significantly shortened for cancer patients receiving more than 20 mg of prednisone (or the equivalent) at any point to treat arthritic side effects from immune checkpoint inhibitors (ICIs), a researcher said here.

Records from 103 such patients treated during 2015-2024 at a major French hospital showed more than doubled overall mortality risk (HR 2.35, 95% CI 1.18-4.69) with a peak daily prednisone-equivalent dose >20 mg, compared with patients never receiving that much, according to Eleonore Mourre, MD, of Hôpital Bicêtre in Paris. Moreover, patients receiving high doses didn’t see any better control of their arthritic symptoms.

Cumulative doses, however, did not significantly affect survival, and progression-free survival was not markedly shortened either by peak doses >20 mg nor large cumulative doses, Mourre told attendees at the European Alliance of Associations for Rheumatology’s (EULAR) annual meeting.

Immune-related adverse effects (irAEs) from ICIs are a major headache in oncology. The products have come as close to wonder drugs in oncology than could have been imagined 20 years ago, at least for those tumor types that respond to them. ICIs work by essentially removing the blindfolds on immune cells that tumor cells are able to put on them, allowing them to go after cancers that have avoided attack. Dramatically lengthened survival, both overall and progression-free, has been documented. The problem is that the newly unleashed immune cells don’t always limit their attack to the tumors. Autoimmune syndromes are common — often mild, though not always, and usually requiring treatment. And inflammatory arthritis is one such irAE.

For the current study, Mourre and colleagues identified patients treated with corticosteroids for ICI-related arthritic symptoms at Hôpital Bicêtre and its affiliated cancer center over a 10-year period after ICI therapy became available. Patients suspected of having mechanical joint problems or flares of underlying, previous autoimmune arthritis were excluded. Steroid doses given during the first 6 months after symptom onset were analyzed along with patients’ overall and progression-free survival. Steroids’ effectiveness in relieving the symptoms was examined as well.

Median patient age was 65 and 40% were female. Some 41% of patients had melanoma and 22% non-small cell lung cancer; oropharyngeal, kidney, and bladder cancer accounted for 11%; and the rest had “other” tumor types. Two-thirds of the patients received a so-called PD-1 inhibitor such as pembrolizumab (Keytruda), while most of the rest had been treated with a combination of anti-PD-1 and anti-PD-1-ligand drugs.

Half of the arthritic conditions resembled polymyalgia rheumatica. Another 30% showed polyarthritis. Inflammation affecting one or a few joints was diagnosed in the remainder. One-third of cases were grade 1, 48% grade 2, and 19% grade 3.

The median peak steroid dose was right at 20 mg (interquartile range 15-40), and the median aggregate dose over 6 months was 1,361 mg (IQR 683-1,950). Some 45% eventually had a disease-modifying anti-rheumatic drug added, usually methotrexate, less often tocilizumab (Actemra). The median time to start steroid dosing was 35 days from symptom onset.

One-year mortality was markedly higher for those patients receiving a peak dose above 20 mg during that 6-month period: about 50%, versus less than 15% for those not getting that much. After the 1-year mark, Kaplan-Meier survival curves declined in parallel for another year, then began to converge; at 4 years, the gap was only about 10 percentage points, with 14 patients still alive.

Kaplan-Meier curves for cumulative dosing, comparing patients above versus below the median of 1,360 mg, also showed a numeric mortality disadvantage for those with higher doses — a maximum of about 25 percentage points at year 3 — but it did not reach statistical significance (P=0.13).

Curves for peak doses >20 mg versus less showed almost no difference in progression-free survival: numerically lower by a few percentage points with high peak doses but not even close to statistical significance.

Meanwhile, Mourre emphasized, giving patients doses above 20 mg didn’t improve their chances of arthritis remission. Their analysis showed a hazard ratio of 0.84 (P=0.28) for achieving remission among patients getting peak doses >20 mg.

Mourre acknowledged the single-center design and small sample size were limitations to the analysis. Data were also lacking on reasons for giving high steroid doses, although she said it was clear that steroids were meant to treat the irAEs, not the cancers.

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