Table 1. Patient response and disease control Global disease control CNS disease control Non-CNS disease control Global objective response CNS objective response Non-CNS objective response Cohort A (n = 51) Cohort B (n = 21) mWHO 9 (18%, 8– 31) 12 (24%, 13–38) 14 (27%, 16–42) 5 (10%, (3–21) 8 (16%, 7–29) 7 (14%, 6–26) irRC 13 (25%, 14–40) 13 (25%, 14–40) 17 (33%, 21–48) 5 (10%, 3–21) 8 (16%, 7–29) 7 (14%, 6–26) mWHO 1 (5%, 0.1–24) 2 (10%, 1–30) 1 (5%, 0.1–24) 1 (5%, 0.1–24) 1 (5%, 0.1–24) 1 (5%, 0.1–24) irRC 2 (10%, (1–30) 2 (10%, 1–30) 2 (10%, 1–30) 1 (5%, 0.1–24) 1 (5%, 0.1–24) 1 (5%, 0.1–24) Data are n (%, 95% CI). irr C, immune-related response criteria; mwh O, modified wh O criteria. r eprinted with permission from Margolin et al. Ipilim- umab in patients with melanoma and brain metastases: an open-label, Phase 2 trial. Lancet Oncology 2012; 13:459–65. 2012; elsevier. Figure 1. Overall survival. r eprinted from Lancet Oncology. Margolin et al. Ipilimumab in patients with melanoma and brain metastases: an open- label, phase 2 trial 13:459–65. 2012 elsevier. of ipilimumab responses in the brain raised the possibility that these assump- tions should be questioned and that the role of cellular immunotherapy for mela- noma brain metastases should be formally evaluated. Although the primary objective of this study was to estimate DCR, safety was also explored considering that initial tumor growth and/or peritumoral inflam- matory changes could cause neurologic complications. Despite early concern that ipilimumab-related inflammation and/or edema in brain lesions would increase mor- bidity, this did not appear to be the case. In fact, there was at least one occasion in which early progressive disease in the CNS was followed by achievement of partial responses—a pattern that has previously been recognized in extracranial disease and is consistent with the mechanism of action and slow kinetics of tumor responses asso- ciated with immunomodulatory therapy. The activity of this regimen without an apparent increase in frequency or emer- gence of unique CNS toxicities was reas- suring evidence that, at least for selected patients, treatment with ipilimumab can be administered with similar efficacy and safety in the brain and extracranial sites. While surgery and/or SRT remains the treatment of choice for most patients at the first occurrence of brain metastasis—in particular for large and/or symptomatic single or oligometastatic disease, ipi- limumab is a promising therapy for those patients whose disease has recurred fol- lowing such frontline therapy and/or who present with multiple, small asymptomatic metastases. The potential impact of sys- temic corticosteroid therapy at the time of initiation of ipilimumab is unknown, but the apparent low level of benefit for such patients (cohort B) in this study suggests that steroid dependence maybe associated with low benefit from ipilimumab.. 1198 OncoImmunology Volume 1 Issue 7