Combining GM-CSF with Radiotherapy Induces Abscopal Responses

Radiotherapy can induce regression of distant nonirradiated tumors, a phenomenon known as an abscopal response. Preclinical studies indicate that abscopal responses are mediated by radiotherapy-induced immune responses, prompting Golden and colleagues to evaluate whether the combination of local radiotherapy and the immune adjuvant granulocyte-macrophage colony-stimulating factor (GM-CSF) would lead to abscopal responses in patients with metastatic tumors receiving chemotherapy or hormonal therapy. Patients with stable or progressive disease were enrolled in a proof-of-principle trial to determine whether concurrent radiotherapy to one metastatic lesion and daily subcutaneous injection of GM-CSF would induce an abscopal response, defined as a greater than 30% decrease in the longest diameter of any nonirradiated lesion. The primary endpoint of the trial was to determine the proportion of patients with an abscopal response, and the secondary endpoints were to evaluate safety and overall survival. Monitoring of immune cells in complete blood counts was added as an exploratory endpoint. Of 41 patients enrolled, 11 (26.8%) experienced an abscopal response, and patients who had an abscopal response had significantly better overall survival compared with those who did not (20.98 months vs. 8.33 months). The combination regimen was well tolerated; although some adverse events were observed, no patient required a dose reduction or needed to discontinue treatment. The exploratory analysis revealed that abscopal responders had a significantly lower baseline median neutrophil-to-lymphocyte ratio than nonresponders, raising the possibility that neutrophils may suppress radiotherapy-induced immune responses and that this ratio might be useful for predicting response to combined radiotherapy and immunotherapy, though prospective longitudinal immunomonitoring is needed. Although a contribution of systemic therapies to the abscopal responses cannot be ruled out, these findings provide evidence that combining immunotherapy with radiotherapy can induce abscopal responses, and provide a rationale for the further clinical evaluation of radiotherapy in combination with immunotherapies in patients with metastatic cancer.

Golden EB, Chhabra A, Chachoua A, Adams S, Donach M, Fenton-Kerimian M, et al. Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours: a proof-of-principle trial. Lancet Oncol 2015;16:795–803.

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