Abstract
The 3-year overall survival (OS) rate of patients with previously treated or untreated stage III or IV melanoma has by now reached 63% using ipilimumab and nivolumab therapy. However, immune-related adverse events (irAEs) of grade 3 or 4 occurred in 59% of patients leading to discontinuation of therapy in 24.5% of patients and one death. Therapy with checkpoint inhibitors could be safer and more effective in combination with hyperthermia and fever inducing therapies. We conducted a retrospective analysis to test the safety and efficacy of a new combination immune therapy in 131 unselected stage IV solid cancer patients with 23 different histological types of cancer who exhausted all conventional treatments. Treatment consisted of locoregional- and whole-body hyperthermia, individually dose adapted interleukin 2 (IL-2) combined with low-dose ipilimumab (0.3 mg/kg) plus nivolumab (0.5 mg/kg). The objective response rate (ORR) was 31.3%, progression-free survival (PFS) was 10 months, survival probabilities at 6 months was 86.7% (95% CI, 81.0–92.8%), at 9 months was 73.5% (95% CI, 66.2–81.7%), at 12 months was 66.5% (95% CI, 58.6–75.4%), while at 24 months survival was 36.6% (95% CI:28.2%; 47.3%). irAEs of World Health Organization (WHO) Toxicity Scale grade 1, 2, 3, and 4 were observed in 23.66%, 16.03%, 6.11%, and 2.29% of patients, respectively. Our results suggest that the irAEs profile of the combined treatment is safer than that of the established protocols without compromising efficacy.
Highlights
IntroductionExtended author information available on the last page of the article
Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Extended author information available on the last page of the articleConcurrent ipilimumab and nivolumab treatment has achieved a 3-year overall survival (OS) rate of 63% for patients with advanced melanoma [1]
The meta-analysis of Xing et al including 48 trials with 7936 patients who were treated with mono-therapeutic nivolumab or nivolumab plus ipilimumab raised the issue that the deleterious effects of severe immune-related adverse events (irAEs) might outweigh the benefit from the addition of ipilimumab [3]
Summary
Extended author information available on the last page of the article. The treatment-related irAEs were reported in 96.8% of patients, 58.5% of which were grade 3 and 4 leading to discontinuation in 24.5% of patients and one death. The meta-analysis of Xing et al including 48 trials with 7936 patients who were treated with mono-therapeutic nivolumab or nivolumab plus ipilimumab raised the issue that the deleterious effects of severe irAEs might outweigh the benefit from the addition of ipilimumab [3]. Predictive biomarkers might help selecting patients who will derive the greatest benefit from ICIs [4]. Selection of patients may not be required if lower ICI dosages are used
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