Since the pivotal cooperative group trials in the 1980’s-90’s,,
high-dose interferon (HDI) has been the standard of adjuvant therapy.
Despite multiple other trials evaluating potential new therapies in
melanoma, HDI remains the only FDA-approved therapy for stage IIB and
III melanoma. Initial reports from the more recent phase III
international trials of modifications of the original HDI regimen linked
the appearance of autoimmunity with improved outcomes of disease. Trials
of high-dose interleukin-2, many years earlier, reported anecdotal
observations that were consistent with the hypothesis that autoimmunity
and clinical benefit of immunotherapies of melanoma are linked with one
another. The only prospectively conducted study examining the appearance
of clinical and laboratory evidence of autoimmunity during HDI therapy
was published by Gogas and colleagues, demonstrating statistically
significant impact on relapse-free survival and overall survival.
Retrospectively conducted studies of different intermediate dosage
regimens of interferon (IFN) have not fully confirmed the linkage of
serological evidence of autoimmunity and improved survival outcomes.
With the emergence of new immunotherapies in treatment of melanoma, this
review highlights the importance of autoimmunity for future applications
in melanoma and reviews significant differences of past studies
evaluating the appearance of autoimmunity during IFN therapy in
high-risk melanoma