Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

the ONA take:

Some patients with advanced melanoma defy the odds of a dismal prognosis, and therefore, the course for any patients with advanced disease should be considered unpredictable, according to a study published in the journal Cancer Management and Research.

For the study, researchers from Royal Adelaide Hospital in Adelaide, Australia, analyzed cases from the database of one clinician. They identified 18 cases of long-term survival ≥3 years’ duration in patients with advanced melanoma. These patients were treated before the availability of novel immunotherapies like pembrolizumab, ipilimumab, and nivolumab.

In these 18 cases, 94% and 61% had survived ≥5 and 10 years, respectively. Researchers found that the median survival duration in patients with metastatic disease was 11 years. At the time of the analysis, 15 patients remained alive, three had died.

Researchers were not able to detect differences between these patients and those with similar patterns of disease so as to determine why these patients had exceptional survival. Some patients had undergone surgery and received multiple regimens of chemotherapy, while others had only undergone surgery. In half of the cases identified, patients had received one or two vaccines, and one patient received no treatment at all.

Cancer Management and Research
Cancer Management and Research

Background: Patients with advanced metastatic melanoma are often confronted with little prospect of medium- to longer-term survival by any currently available therapeutic means. However, most clinicians are aware of exceptional cases where survival defies the notion of futility. Prolonged survival from immunotherapies, including interleukin-2, vaccines and antibodies to cytotoxic lymphocyte antigen-4, and programmed death-1 receptor inhibitory monoclonal antibody, implies a role for immune system modulation. We aimed to identify cases where exceptional survival from advanced melanoma occurred prior to recent novel therapies to facilitate better understanding of this phenomenon.

Methods: Cases of long-term survival of ≥3 years' duration (from diagnosis of metastatic disease) were identified from the database of one clinician; these cases were treated before the availability of newer immunotherapies, and they were documented and examined. A literature search for reported outcome measures from published studies using older and recent therapies for advanced melanoma was conducted to enable the comparison of data.

Results: Eighteen cases were identified that identified survival of ≥3 years' duration from metastatic disease (12 American Joint Committee on Cancer [AJCC] Stage IV cases; six AJCC III cases) diagnosis. These were assessed and reported to detail the clinical course. Standard clinical prognostication methods predicted high risk of early mortality in those patients. No identifiable differences could be detected between these and other patients with similar patterns of disease. At evaluation, 17 patients (94%) had survived ≥5 years, and eleven patients (61%) had survived ≥10 years (range: 3–15 years). The median survival duration with metastatic disease was 11 years; 15 remained alive and three had died. Published studies of melanoma therapies were tabled for comparison.

Conclusion: The fact that 18 cases of exceptional survival in advanced melanoma were identified is remarkable in itself. Even with recent therapies, the factors for improved survival remain enigmatic; however, one apparent common denominator in most cases was the persistent use of repeated therapies to reduce tumor bulk, induce tumor necrosis, and/or cause immunostimulation. These cases are instructive, suggesting manipulation of an established, endogenous, existing immune response. These observations provide practical evidence that the course for any patient with advanced melanoma at the outset should be considered unpredictable, open to immunomanipulation, and thus not uniformly fatal. The findings were compared and interpreted with reported newer immunotherapeutic approaches.


Keywords: advanced melanoma, clinical responses, immunotherapy, prolonged survival
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