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Advanced melanoma patients who progressed after Ipilimumab immunotherapy: abscopal effects of radiotherapy


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 radiotherapy could potentially synergize.

Researchers have reported the outcome of patients with advanced melanoma treated with the immune checkpoint blockade monoclonal antibody antagonist, Ipilimumab ( Yervoy ) followed by radiotherapy.
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 radiotherapy and were selected for analysis.

Among 21 patients, 13 patients ( 62% ) received radiotherapy to treat metastases in the brain and 8 received radiotherapy 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 radiotherapy to an abscopal response was 1 month ( range 1-4 ).

Median overall survival for all 21 patients was 13 months ( range 6-26 ). Median overall survival 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 radiotherapy 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 radiotherapy after Ipilimumab may lead to abscopal responses in some patients with advanced melanoma correlating with prolonged overall survival.
The data also suggest that local responses to radiotherapy may be predictive of abscopal responses. ( Xagena )

Grimaldi AM et al, Oncoimmunology 2014;3:e28780

XagenaMedicine_2014



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