A Retrospective Analysis of Safety and Outcome of Radiotherapy Given Following Treatment with Ipilimumab for Metastatic Melanoma

Abstract

ABSTRACT Aim: Case reports have documented abscopal effects of radiation in patients with melanoma, which may be enhanced by combining radiotherapy with immunomodulatory drugs. Ipilimumab upregulates the T cell immune response by blocking CTLA4, stimulating the immune system to target malignant cells. Here we assess the safety and efficacy of palliative radiotherapy following treatment with ipilimumab. Methods: The records of all patients with metastatic melanoma receiving palliative radiotherapy after ipilimumab between September 2010 and January 2013 at University Hospital Southampton NHS Trust were reviewed. Imaging was reassessed by radiologists experienced in tumour assessment and RECIST criteria 1.1 were used to evaluate tumour response both inside and outside the radiation field. Where the radiotherapy field was not imaged following treatment, symptomatic benefit was used. Results: 21 individuals received radiotherapy after ipilimumab between the specified dates. 10 were male; mean age at ipilimumab treatment was 57.6 years; all were ECOG performance status 0 or 1. Primary lesions were cutaneous 18 cases, ocular 1, unknown 2. Median progression free survival following ipilimumab treatment was 92 days; median time between first ipilimumab dose and start of radiotherapy was 74 days (range 3–175), radiotherapy was concurrent in some cases. Radiotherapy sites were brain (7), spine (2) and other (11). 11 individuals had imaging assessment of tumour response within the radiotherapy field, of which 4 had a partial response, 1 individual had on-going response in the radiotherapy field 21 months after irradiation. 5 of the remaining 10 were documented as having a good symptomatic response, meaning overall 42% derived clinical benefit from radiotherapy. There were no cases of radiotherapy inducing disease response outside the radiotherapy field. No individuals experienced radiation toxicity greater than CTCAE grade 2. Conclusions: In our series palliative radiotherapy was safe to use after ipilimumab. 42% of patients derived clinical benefit, one of whom has an ongoing response 21 months post treatment. There were however no cases of abscopal effect. Disclosure: M. Wheater: Support for conference attendance from BMS; C. Ottensmeier: BMS unrestricted clinical trial grant funding, consultancy for BMS and sponsorship for meeting attendance. All other authors have declared no conflicts of interest.