2545 - Utilization of Brain-Directed Therapy for Patients with Melanoma Brain Metastases Treated with Ipilimumab and Nivolumab

T. Kleber¹, S. Srinivasan², M. Davies³, H. A. Tawbi³, I. Glitza³, S. Ferguson⁴, and T. Beckham¹; ¹Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ²University of Texas McGovern School of Medicine, Houston, TX, ³Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁴Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX

Purpose/Objective(s): Ipilimumab and nivolumab (Ipi/Nivo) combination immunotherapy has been shown to lead to durable responses in >50% of asymptomatic patients with melanoma brain metastases (MBM). However, questions remain regarding the indications for upfront vs. deferred local brain-directed therapy (BDT) for patients with newly diagnosed MBM starting Ipi/Nivo. Materials/

Methods: Under an IRB-approved protocol, we retrospectively reviewed patients treated at our institution for MBM between 2018 and 2021 with Ipi/Nivo as part of their initial treatment. Patients without any post-Ipi/Nivo brain imaging were excluded. Data were collected regarding patient demographics, history, disease status, treatment details, and outcomes. Upfront BDT was defined as intracranial radiation and/or surgery initiated before or within six weeks after the start of Ipi/Nivo, provided the decision to initiate BDT was not based on a post-Ipi/Nivo diagnostic scan. BDT occurring at later time points was defined as salvage BDT. Intracranial progression free survival (IPFS) and overall survival (OS) were calculated from MBM diagnosis. Adjusted hazard ratios (aHR) were calculated using multivariable Cox regression models, which included covariates associated with treatment group or outcome by a threshold of p<0.20.
Results: 94 MBM patients were treated initially with Ipi/Nivo. The median age at MBM diagnosis was 59 (range 20-88); 63 (67.0%) were male, and 43 (54.7%) received = 5 doses of immunotherapy. 57 patients (60.6%) received upfront BDT: 47 (82.5%) with stereotactic radiosurgery, 8 (14%) whole brain radiation therapy, and 29 (50.8%) craniotomy. Among patients without upfront BDT (n=37; 39.4%), 20 received salvage BDT at a median 3.8 mos after starting Ipi/Nivo. Patients that received upfront BDT had worse Karnofsky Performance Status (p=0.012), larger maximum MBM size (p<0.001), and were more likely to be symptomatic (p<0.001), but the number of brain metastases was not significantly different between groups (p=0.302). Median IPFS for patients treated with and without upfront BDT was 12.3 mos (95% CI 7.1-26.2) and 11.5 mos (95% CI 4.4-not reached [NR]), respectively, with an aHR of 1.32 (95% CI 0.59-2.95, p=0.50). Median OS for patients treated with and without upfront BDT was 40.5 mos (95% CI, 23.5-NR) and 39.9 mos (95% CI, 22.0-NR), respectively, with an aHR of 1.36 (95% CI 0.61-3.02, p=0.45).
Conclusion: A multi-disciplinary discussion is essential for patients with newly diagnosed MBM starting Ipi/Nivo. At our institution, BDT is often deferred for well-selected low-risk patients, especially those with high performance status, small brain metastases, and no MBM-related symptoms. When deferring BDT, close surveillance is crucial since short-term intracranial progression and the need for salvage BDT is common. Further research is needed to better define patient subsets that would most benefit from upfront vs. deferred BDT.