Nora Sundahl1, Katrien De Wolf2, Vibeke Kruse3, Annabel Meireson4, Dries Reynders5, Els Goetghebeur5, Mireille Van Gele4, Reinhart Speeckaert4, Benjamin Hennart6, Lieve Brochez7, Piet Ost2. 1. Department of Radiation Oncology and Experimental Cancer Research, University Hospital Ghent, Ghent, Belgium; Immuno-Oncology Network Ghent, Ghent, Belgium. Electronic address: nora.sundahl@ugent.be. 2. Department of Radiation Oncology and Experimental Cancer Research, University Hospital Ghent, Ghent, Belgium; Immuno-Oncology Network Ghent, Ghent, Belgium. 3. Immuno-Oncology Network Ghent, Ghent, Belgium; Department of Medical Oncology, University Hospital Ghent, Ghent, Belgium. 4. Department of Dermatology and Dermatology Research Unit, University Hospital Ghent, Ghent, Belgium. 5. Department of Applied Mathematics, Computer Science and Statistics & Stat-Gent CRESCENDO Consortium, Ghent University, Ghent, Belgium. 6. Centre Hospitalier Universitaire Lille, Unité Fonctionelle de Toxicologie, Lille, France. 7. Immuno-Oncology Network Ghent, Ghent, Belgium; Department of Dermatology and Dermatology Research Unit, University Hospital Ghent, Ghent, Belgium.
Abstract
PURPOSE: To report the results of a phase 1 trial evaluating the safety of the ipilimumab/radiation therapy combination in patients with metastatic melanoma. PATIENTS AND METHODS: Thirteen patients with metastatic melanoma were enrolled. Trial treatment consisted of 4 cycles of ipilimumab in combination with concurrent dose-escalated high-dose radiation therapy to 1 lesion administered before the third cycle of ipilimumab. RESULTS: Grade 3 or 4 ipilimumab-related adverse events occurred in 25% of patients. The maximum tolerated radiation therapy dose was not reached. Local control of the irradiated lesions was achieved in 11 of 12 irradiated patients (1 patient had progressive disease before irradiation and dropped out of the trial). Evaluation of the nonirradiated lesions demonstrated that 3 of 13 patients experienced clinical benefit, with 1 patient developing a partial response and 2 patients having confirmed stable disease. Immunomonitoring data showed that in patients without clinical benefit, factors linked to immunotolerance increased early after the initiation of ipilimumab, suggesting that early initiation of radiation therapy might be more effective if combined with ipilimumab. CONCLUSIONS: Our findings suggest that the combination of ipilimumab and high-dose radiation therapy is feasible and safe.
PURPOSE: To report the results of a phase 1 trial evaluating the safety of the ipilimumab/radiation therapy combination in patients with metastatic melanoma. PATIENTS AND METHODS: Thirteen patients with metastatic melanoma were enrolled. Trial treatment consisted of 4 cycles of ipilimumab in combination with concurrent dose-escalated high-dose radiation therapy to 1 lesion administered before the third cycle of ipilimumab. RESULTS: Grade 3 or 4 ipilimumab-related adverse events occurred in 25% of patients. The maximum tolerated radiation therapy dose was not reached. Local control of the irradiated lesions was achieved in 11 of 12 irradiated patients (1 patient had progressive disease before irradiation and dropped out of the trial). Evaluation of the nonirradiated lesions demonstrated that 3 of 13 patients experienced clinical benefit, with 1 patient developing a partial response and 2 patients having confirmed stable disease. Immunomonitoring data showed that in patients without clinical benefit, factors linked to immunotolerance increased early after the initiation of ipilimumab, suggesting that early initiation of radiation therapy might be more effective if combined with ipilimumab. CONCLUSIONS: Our findings suggest that the combination of ipilimumab and high-dose radiation therapy is feasible and safe.
Authors: Ahmad A Tarhini; Sandra J Lee; Xiaoxue Li; Uma N M Rao; Arun Nagarajan; Mark R Albertini; Jerry W Mitchell; Stuart J Wong; Mark A Taylor; Noel Laudi; Phu V Truong; Robert M Conry; John M Kirkwood Journal: Clin Cancer Res Date: 2018-11-12 Impact factor: 12.531
Authors: Amit Maity; Rosemarie Mick; Ramesh Rengan; Tara C Mitchell; Ravi K Amaravadi; Lynn M Schuchter; Daniel A Pryma; Dana M Patsch; Alisha P Maity; Andy J Minn; Robert H Vonderheide; John N Lukens Journal: Oncoimmunology Date: 2021-01-31 Impact factor: 8.110