Programmed cell death protein-1 (PD-1) inhibitor therapy in patients with advanced melanoma and preexisting autoimmunity or ipilimumab-triggered autoimmunity

Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): Ralf Gutzmer, Anika Koop, Friedegund Meier, Jessica C. Hassel, Patrick Terheyden, Lisa Zimmer, Lucie Heinzerling, Selma Ugurel, Claudia Pföhler, Anja Gesierich, Elisabeth Livingstone, Imke Satzger, Katharina C. Kähler
AimProgrammed cell death protein 1 (PD-1) inhibitors are a common treatment strategy for metastatic melanoma and other tumour entities. Clinical trials usually exclude patients with preexisting autoimmune diseases, thus experience with PD-1 inhibitor (PD-1i) in this patient population is limited.Patients and methodsMetastatic melanoma patients with preexisting autoimmune disorders or previous ipilimumab-triggered immune-related adverse events (irAE) undergoing treatment with PD-1i from seven German skin cancer centres were evaluated retrospectively with regard to flare of the preexisting autoimmunity and development of new, not preexisting irAE as well as response to PD-1i therapy.ResultsIn total, 41 patients had either preexisting autoimmunity (n=19, group A, including two patients with additional ipilimumab-triggered autoimmune colitis) or ipilimumab-triggered irAE (n=22, group B). At PD-1i therapy initiation, six patients in group A and two patients in group B required immunosuppressive therapy. In group A, a flare of preexisting autoimmune disorders was seen in 42% of patients, new irAE in 16%. In group B, 4.5% of patients showed a flare of ipilimumab-triggered irAE and 23% new irAE. All flares of preexisting autoimmune disorders or irAE were managed by immunosuppressive and/or symptomatic therapy and did not require termination of PD-1i therapy. tumour responses (32% in group A and 45% in group B) were unrelated to occurrence of autoimmunity.ConclusionWhile preexisting autoimmunity commonly showed a flare during PD-1i therapy, a flare of ipilimumab-triggered irAE was rare. Response rates were above 30% and unrelated to irAE. PD-1i therapy can be considered in patients with autoimmune disorders depending on severity and activity of autoimmunity.

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Key message: Nineteen patients with preexisting autoimmunity (group A) and 22 patients with ipilimumab-triggered immune-related adverse events (irAE) (group B) were treated with PD-1 inhibitors (PD-1i). All flares of preexisting autoimmunity (group A: 42%, group B: 4.5%) and other irAE (group A: 16%, group B: 23%) were manageable by immunosuppressive and/or symptomatic therapy and did not require termination of PD-1i therapy. Overall response rates were 32% in group A and 45% in group B, and were not correlated to the occurrence of autoimmunity. Thus, patients with preexisting autoimmunity or ipilimumab-triggered irAE are not generally required to be excluded from PD-1i therapy.


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