Combining radiotherapy and ipilimumab induces clinically relevant radiation-induced abscopal effects in metastatic melanoma patients: A systematic review.

Background: In the last years, limited studies have described that radiotherapy could produce important distant responses in unirradiated sites, the so-called "abscopal effect". Recent evidence suggests that radiotherapy induces antigen release from tumor, in this way activating the immune system. However, radiotherapy alone is rarely enough to induce the systemic response requested for control of the metastases. With the advent of immunotherapy, the immune checkpoint inhibitors (ICI) have demonstrated impressive efficacy in various metastatic cancers. Currently, preclinical and clinical studies have reported a significant increase of abscopal responses in patients treated with the combination of radiotherapy and ICI. The purpose of this review was summarizing the clinical studies combining radiotherapy and ipilimumab (ipi), particularly focusing on abscopal responses.

Methods and Materials: Databases of Medline (via Pubmed) from 2009 to June 2, 2017 were reviewed to obtain English language studies reporting clinical abscopal effect in the combination of radiotherapy with exclusive ipi in metastatic melanoma cancers. Included studies reported the abscopal effect as a primary endpoint, and as secondary endpoint included overall survival and toxicity.

Results: A total of 16 studies met the inclusion criteria. These studies included a total of 451 patients, and in 5/16 studies the patients were treated on research protocols and followed-up prospectively. The median reported abscopal effect and OS were 26.5% and 19 months, respectively. The median toxicity ≥ Grade 3 was 18.3% ranged from 10% to 20%.

Conclusion: Early clinical outcomes reports suggest that the combination of ipilimumab and RT may improve survival in metastatic melanoma patients. The abscopal responses become a clinically relevant effect of such combination and should be studied in controlled randomized trials.