Pseudoprogression in Melanoma Therapy


John Kirkwood, MD, PhD, addresses the idea of pseudoprogression seen in melanoma therapy.

Matthew Fowler: How big of a concern in your practice is pseudoprogression? What do you do when you suspect progression but aren’t sure?

John Kirkwood, MD, PhD: It’s an interesting issue. We all wanted to believe that by inducing inflammation, we might see tumor enlargement that was spurious, was not related to the tumor cells themselves being more bulky and larger but was because of the inflammatory infiltrate, which would lead to pseudoprogression. I must say that I’ve been a doubting Thomas in regard to this phenomenon, especially with PD-1. It may have been more prevalent and more valid with CTLA4, but CTLA4 got us benefits—measurable tumor regression in a very small fraction; 10% would have been a literal view of that. The PD-1 response rate, 35%, 40%, is infrequently accompanied by pseudoprogression.

The best way to interpret pseudoprogression vs real progression is how the patient feels. In a patient who feels remarkably better, is a month out on therapy, and has what seems to be palpable enlargement of a lymph node, it’s perfectly fine to continue until the usual benchmark of 2 or 3 months of therapy. In patients who have 1 month of therapy, a larger palpable lymph node, and who feel terrible, it’s worthy of imaging reassessment for a global assessment of the disease, and then for consideration of therapies that may turn the ship around. It sounds much more like real progression than pseudoprogression.

This transcript has been edited for clarity.

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