Anti-PD-1 Therapy Supported In Advanced Melanoma Patients With Immune Complications

Pre-existing autoimmune disease and immune reactions to ipilimumab need not rule out programmed cell death protein 1 inhibitor therapy for advanced melanoma

medwireNews: Programmed cell death protein 1 (PD-1) inhibitor therapy is feasible in advanced melanoma patients with pre-existing autoimmune disorders or prior immune-related adverse events (irAEs) associated with ipilimumab, research suggests.

“[A]nti-PD-1 [therapies] induced relatively frequent immune toxicities, but these were often mild, easily managed, and did not necessitate discontinuation of therapy, and a significant proportion of patients achieved clinical responses”, say Alexander Menzies, from Melanoma Institute Australia in Sydney, New South Wales, and co-authors.

“The results support that anti-PD-1 [agents] can be administered safely and can achieve clinical benefit in patients with preexisting [autoimmune disorders] or prior major irAEs with ipilimumab.”

The study, published in the Annals of Oncology, describes the outcome of 119 patients with immune complications who were treated with pembrolizumab or nivolumab at 13 hospitals between 2012 and 2015, a population who are traditionally excluded from clinical trials of such treatments. The patients were followed-up for a median of 4.7 months and had a median progression-free survival of 6.8 months.

Overall, 33% of the 52 patients with a pre-existing autoimmune disorder responded to anti-PD-1 treatment, as did 40% of the 67 patients who had required immunosuppression after developing irAEs during ipilimumab therapy.

Review of autoimmune flare during anti-PD-1 therapy showed this occurred in seven of the 13 patients with rheumatoid arthritis and three of the eight patients with psoriasis. All three patients with polymyalgia rheumatica experienced flare, as did both patients with Sjogren’s syndrome and both patients with immune thrombocytopenic purpura.

By contrast, none of the six patients with gastrointestinal autoimmune disorders or the five patients with neurological disorders experienced a flare during PD-1 inhibitor treatment.

Although just 4% of patients discontinued PD-1 inhibitor therapy because of flare, 29% did develop other irAEs, resulting in discontinuation in a further 8%.

The researchers note that the response rate was comparable in patients with and without a flare but was lower in patients who were using immunosuppression therapy at the start of the trial. But they emphasize: “This result must be viewed with caution given the small numbers of patients involved, the heterogeneous population, and the retrospective nature of this study.” 

irAEs recurred in 3% of the patients with a prior reaction to ipilimumab, while new irAEs were reported in 34%, including grade 3 or 4 events in 21%. PD-1 inhibitor treatment was discontinued in 12% of patients.

Alexander Menzies et al conclude: “Clinicians may consider anti-PD-1 antibodies for appropriately selected patients with pre-existing autoimmune disease or prior severe irAE with ipilimumab, provided there is close monitoring and adherence to standard irAE treatment algorithms, and in discussion with experts in major immunotherapy centers.”

Reference

Menzies AM, Johnson DB, Ramanujam S, et al. Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Ann Oncol; Advance online publication 29 September 2016. doi: 10.1093/annonc/mdw443

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