Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy

Abstract

Cancer radiotherapy (RT) may induce what is referred to as the “abscopal effect,” a regression of non-irradiated metastatic lesions distant from the primary tumor site directly subject to irradiation. This clinical response is rare, but has been surmised to be an immune-mediated phenomenon, suggesting that immunotherapy and RT could potentially synergize. Here, we report the outcome of patients with advanced melanoma treated with the immune checkpoint blockade monoclonal antibody antagonist, ipilimumab followed by RT. Patients were selected for enrollment at the National Cancer Institute “Fondazione G.Pascale” through the expanded access program in Italy. Those who experienced disease progression after ipilimumab thus received subsequent RT and were selected for analysis. Among 21 patients, 13 patients (62%) received RT to treat metastases in the brain and 8 received RT directed at extracranial sites. An abscopal response was observed in 11 patients (52%), 9 of whom had partial responses (43%) and 2 had stable disease (10%). The median time from RT to an abscopal response was 1 month (range 1–4). Median overall survival (OS) for all 21 patients was 13 months (range 6–26). Median OS for patients with abscopal responses was extended to 22.4 months (range 2.5–50.3) vs. 8.3 months (range 7.6–9.0) without. A local response to RT was detected in 13 patients (62%) and, of these, 11 patients (85%) had an abscopal response and abscopal effects were only observed among patients exhibiting a local response. These results suggest RT after ipilimumab may lead to abscopal responses in some patients with advanced melanoma correlating with prolonged OS. Our data also suggest that local responses to RT may be predictive of abscopal responses. Further research in larger randomized trials is needed to validate these results.

Radiation Therapy for Melanoma

“…Median overall survival for those patients who had an abscopal response was 22.4 months versus 8.3 months for those without a response. Larger prospective studies are required to bolster this small but impressive report (160). This effect is believed mediate through immune response.…”

“…Besides local effect, radiation may also impact systemic response. Abscopal effect refers to the infrequently reported tumor regression of a secondary site following RT to a separate primary site (157)(158)(159)(160)(161). One recent report analyzed 21 patients with advanced melanoma treated with ipilimumab followed by RT and observed an abscopal response in 11 patients (52%) with the median time of 1 month from RT to response.…”

Irradiation and immunotherapy: From concept to the clinic

“…80 One of the largest reports of RT-induced immune stimulation describes 21 patients with advanced melanoma who received RT after progressing through ipilimumab. 81 After intracranial (62%) and extracranial RT, 52% of patients demonstrated an abscopal effect, defined as an immune-related and tumor-inhibitory effect observed outside of the irradiated field. Most patients had PRs (n 5 9), whereas 2 patients had SD for at least 4 41 all whom had 6 metastases.…”

Will melanoma be curable? Perspectives in melanoma therapy

“…Miután a tumorsejtek elpusztulnak és megrepednek, a tumor-specifikus antigének és a GM-CSF felszabadulása további szisztémás tumorellenes választ vált ki (25). Az immunonkológiai gyógyszerek T-VEC-el tör-ténő kombinációjának szinergista hatásáról irodalmi adatok állnak rendelkezésre (26). Egy jelenleg is folyamatban lévő fázis I/II-es vizsgálatban 18 beteget kezeltek T-VEC + ipilimumab kombinációval.…”