A Prospective Clinical Trial Combining Radiation Therapy with Systemic Immunotherapy in Metastatic Melanoma
Mené sur 22 patients atteints d'un mélanome de stade IV, cet essai évalue la tolérabilité d'un traitement combinant radiothérapie et ipilimumab
Purpose : Local radiation therapy (RT) in combination with systemic anti-CTLA-4 immunotherapy may enhance induction of systemic anti-melanoma immune responses. The primary objective of this trial was to assess the safety and efficacy of combining ipilimumab with RT in patients with stage IV melanoma. Secondary objectives included laboratory assessment of induction of anti-melanoma immune responses. Materials/Methods : In our prospective clinical trial, 22 patients with stage IV melanoma were treated with palliative RT and ipilimumab for 4 cycles. RT to 1-2 disease sites was initiated within 5 days after starting ipilimumab. Patients had >1 nonirradiated metastasis measuring >1.5 cm for response assessment. Tumor imaging studies were obtained at baseline, 2-4 weeks following cycle 4 of ipilimumab, and every 3 months until progression. Laboratory immune response parameters were measured before and during treatment. Results : Combination therapy was well-tolerated without unexpected toxicities. Eleven patients (50.0%) had clinical benefit from therapy, including complete and partial responses (CR, PR) and stable disease (SD) at median follow-up of 55 weeks. Three (27.3%) achieved an ongoing systemic CR at median follow-up of 55 weeks (range 32-65), and 3 (27.3%) had initial PR for a median of 40 weeks. Analysis of immune response data suggests a relationship between elevated CD8-activated T-cells and response. Conclusion : This is the second prospective clinical trial of treatment of metastatic melanoma with the combination of RT and systemic immunotherapy and the first using this sequence of therapy. Results from this trial demonstrate that a subset of patients can benefit from combination therapy, arguing for continued clinical investigation into the use of radiation therapy in combination with immunotherapy including PD-1 inhibitors, which may have the potential to be even more effective in combination with radiation.