Opposing effects of immunotherapy in melanoma using multisubtype interferon-alpha – can tumor immune escape after immunotherapy accelerate disease progression?

With checkpoint inhibitors, patients with advanced melanoma display durable responses suggesting cure of disease. However, the immune system has dual roles in cancer; while the immune system may eradicate a tumor, a subtotal elimination may selectively destroy immunogenic cells driving the proliferation of non-immunogenic tumors. Here, we performed a retrospective analysis of results obtained in a controlled trial of patients with melanoma treated with adjuvant, multisubtype interferon-α. The survival curves displayed a late divergence for treated patients and controls resulting in substantially higher estimates of overall (OS) and relapse-free survival (RFS) rates among treated patients after 9 y of follow up. Interestingly, succumbing patients in the treatment group displayed reduced time between relapse and death, suggesting therapy-induced acceleration of disease progression. These findings suggest that effective immunotherapy that induces durable, curative responses in some patients, may potentially accelerate disease progression in others, highlighting the importance of developing advanced strategies to identify patients who are likely to benefit from immunotherapy.