The interesting findings emerging from recent immunotherapeutic agents and strategies appear to be strongly indicative that modulation of a pre-existing, underlying, endogenous immune response is naturally occurring within the patient against their cancer. It is therefore highly likely that both the findings arising from the repeated therapies reported in our present series, and those being reported using current repetitious immunotherapeutic and pathway blockade therapy approaches, appear to cause progressive immunomodulation, perhaps by effectively “synchronising”, “directing”, or “re-focussing” the patient’s in vivo immune response against their cancer.42,43 Better serial blood biomarker analysis and improvement of the accuracy of the timing of therapeutic intervention(s) both appear to be very promising approaches toward obtaining better “synchronization” of therapies with pre-existing in vivo immune responses to thereby improve clinical efficacy.21,22,42–44


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CONCLUSION

Some patients show long-term survival despite advanced melanoma having the reputation of being associated with a particularly dismal prognosis. Clinical course data for 18 cases demonstrates that some patients do defy the odds, in some cases even without therapy, to mount an effective response against their cancer. A combination of selective and combined therapies tailored to the individual patient appears to be capable of modulating the immune response and disease level in a favorable direction for a better outcome. These remarkable cases provide clinical insight into the mechanisms that underpin the better clinical control of metastatic melanoma, and perhaps cancer more generally. Even after failed treatment attempts, long-term patient survival may still be evidenced in a remarkable number of cases in clinical practice. Recent data from the treatment of patients using “pure” immunotherapeutic approaches, such as IL-2, CTLA-4/PD-1 antibody therapies, and repetitive vaccination, would reinforce the notion that restimulation of the immune response in the patient can be remarkably effective in inducing long-term survival.

Although the outlook on metastatic melanoma may seem dismal, cases such as those reported should provide patients with tangible evidence and some hope that their fight against advanced melanoma is not uniformly, nor irrevocably, futile. Physicians, while being realistic, should encourage patients not to become disheartened by failed treatment attempts. Some individuals, even after multiple failed treatment attempts, do ultimately defy their metastatic disease to outlive their initial predicted prognosis, as our findings demonstrate. Continued persistent therapies appear remarkably pivotal. Moreover, newer immunotherapies and new approaches for applying these clinically offer the very tangible prospects of improving the manipulation of endogenous immune responses in patients with advanced cancer.42–44

Disclosure

The authors report no conflicts of interest in this work.

Brendon J Coventry, Dominique Baume, Carrie Lilly
Discipline of Surgery, Royal Adelaide Hospital, University of Adelaide, Adelaide, SA, Australia

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