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Background Treatment options for patients with melanoma brain metastasis (MBM) have changed significantly in the last decade. Few studies have evaluated changes in outcomes and factors associated with survival in MBM patients over time. The aim of this study is to evaluate changes in clinical features and overall survival (OS) for MBM patients. Methods Patients diagnosed with MBMs from 1/1/2009 to 12/31/2013 (Prior Era; PE) and 1/1/2014 to 12/31/2018 (Current Era; CE) at The University of Texas MD Anderson Cancer Center were included in this retrospective analysis. The primary outcome measure was OS. Log-rank test assessed differences between groups; multivariable analyses were performed with Cox proportional hazards models and recursive partitioning analysis (RPA). Results A total of 791 MBM patients (PE, n = 332; CE, n = 459) were included in analysis. Median OS from MBM diagnosis was 10.3 months (95% CI, 8.9–12.4) and improved in the CE vs PE (14.4 vs 10.3 months, P Conclusions OS and factors associated with OS have changed for MBM patients. This information can inform contemporary patient management and clinical investigations.

Another benefit of dietary fiber The gut microbiome can modulate the immune system and influence the therapeutic response of cancer patients, yet the mechanisms underlying the effects of microbiota are presently unclear. Spencer et al . add to our understanding of how dietary habits affect microbiota and clinical outcomes to immunotherapy. In an observational study, the researchers found that melanoma patients reporting high fiber (prebiotic) consumption had a better response to checkpoint inhibitor immunotherapy compared with those patients reporting a low-fiber diet. The most marked benefit was observed for those patients reporting a combination of high fiber consumption and no use of over-the-counter probiotic supplements. These findings provide early insights as to how diet-related factors may influence the immune response. —PNK

9540 Background: The management and OS of pts with metastatic melanoma have improved due to new systemic therapies. However, relatively little is known about the use of these treatments (tx) and their association with OS in pts with MBMs. We reviewed a large cohort of MBM pts to assess how pt demographics, disease characteristics, and MBM tx impact OS in the current era. Methods: Under an institutional review board-approved protocol, retrospective data were curated and analyzed from pts diagnosed with, and received tx for, MBM from 2014 to 2018 at the MD Anderson Cancer Center (MDA). Pts diagnosed with uveal or mucosal melanoma or other cancers were excluded. Pt demographics; timing and features of initial melanoma dx; timing and features of initial MBM dx; prior, initial and subsequent tx; and OS were collected. OS was determined from MBM dx to last clinical follow-up (FU). Pts alive at last FU were censored. The Kaplan-Meier method and log-rank test were used to estimate OS and to assess univariate group differences, respectively. Multivariable (MV) associations of OS with variables of interest were investigated with Cox proportional hazards models. Initial treatment of MBM was assessed as a time-varying covariate. All statistical tests used a significance level of 5%. Results: A total of 401 MBM pts were identified. The median age at MBM dx was 61; 67% were male and 46% had a BRAF V600 mutation. At MBM diagnosis dx, most (70%) pts were asymptomatic; 70% had concurrent uncontrolled extracranial disease; 36% had elevated serum LDH. Prior tx included immunotherapy (IMT) for 39% and targeted therapy (TTX) for 17%. The median number of MBMs was 2; 31% had > 3 MBMs. Median largest MBM diameter was 1.0 cm, 9% had MBM > 3.0 cm, and 5% had concurrent leptomeningeal disease (LMD). Tx received after MBM dx included stereotactic radiosurgery (SRS; 53% as initial tx for MBM, 67% at any time after MBM dx), whole brain radiation therapy (WBRT; 16%, 35%), craniotomy (12%, 19%), IMT (37%, 74%), and/or TTX (22%, 40%). 31% received steroids during initial MBM tx. At a median FU of 13.4 (0.0 - 82.8) months (mos), the median OS was 15.1 mos, and 1- and 2-year OS rates were 56% and 40%. Notably, gender, time to MBM dx, and BRAF status were not associated with OS (univariate analysis). On MV analysis, clinical features associated with worse OS included increased age, increased primary tumor thickness, elevated LDH, > 3 MBMs, +LMD, +symptoms, and prior tx with IMT. Among tx used at any time after MBM dx, WBRT (HR 1.9, 95% CI 1.5-2.5) was associated with worse OS; SRS (HR 0.7, 95% CI 0.5-0.8) and IMT (HR 0.6, 95% CI 0.5-0.8) were associated with improved OS. Conclusions: In one of the largest cohorts of MBM pts described to date, OS has improved in MBM pts in the current era. Prognostic factors for OS include pt age, primary tumor and MBM features, prior tx, and tx for MBM. Additional analyses to assess the interaction of tx, disease features, and OS will be presented.

Background Immune related adverse events (irAEs) are common side effects of checkpoint inhibitory (CPI) therapies targeting CTLA-4 and PD-1/PD-L1. Grover’s disease is an uncommon dermatologic condition with unclear pathogenesis previously reported as an irAE with ipilimumab. Case Presentation We report an additional case of ipilimumab-induced Grover’s disease. Interestingly, this dermatologic side effect did not appear with use of anti-PD-1 therapy in our patient. Immune analysis was performed and suggests a possible role of Th2 cells in its patholgenesis. Conclusion This case suggests that Grover's disease is an irAE induced by Ipilimumab. Our immune analysis suggests that Th2 cells may be pathogenic mediators which warrants further study.

Background: There is a growing appreciation for the GM in response to melanoma therapy. Recent work identified a favorable (T1) GM signature associated with checkpoint benefit. However, little is known about how lifestyle factors may influence features of the GM or about the influence of the GM on therapeutic outcomes to other common melanoma therapies. Methods: We prospectively collected fecal samples melanoma patients at MD Anderson Cancer Center and characterized the GM via 16S rRNA sequencing (n=146). In a subset initiating systemic therapy (n= 113), we also collected baseline diet information via the NCI dietary screener questionnaire, and probiotic and antibiotic use and followed for response (RECISTv1.1). We compared GM beta diversity (BD)(Bray-Curtis) with ANOSIM and descriptive statistics and Wilcoxon tests were applied to alpha diversity (AD)(Chao1) among treatment response groups. Spearman correlation was used to test relationships of dietary groups and GM composition. Univariate and multivariate logistic regression models were used to determine the individual and joint effects of lifestyle factors on response. Receiver operating characteristic (ROC) curves were constructed for area under the curve (AUC) quantification. Results: Considering all treatment groups, baseline AD was highest in patients with complete/partial response (mean=355), compared to patients with stable (mean=330) and progressive disease (mean=318). The GM did not significantly differ by age, sex or BMI. Report of probiotic (42%) and antibiotic (29%) use at baseline was associated with lower AD (p=0.02). Whole grains and overall diet quality correlated positively with pro-response bacteria, added sugars and processed meat negatively correlated. GM community structure (BD) differed by high and low fiber intake (p Conclusion: AD of the GM varies by response regardless of treatment type. While preliminary, this data points to the idea that the GM in melanoma patients may be negatively influenced by probiotics and could be targeted by dietary manipulation. Larger prospective and interventional studies are needed to assess the relationships between host lifestyle factors, the GM and response to melanoma therapies. Citation Format: Christine N. Spencer, Vancheswaran Gopalakrishnan, Jennifer McQuade, Miles C. Andrews, Beth Helmink, M.A. Wadud Khan, Elizabeth Sirmans, Lauren Haydu, Alexandria Cogdill, Elizabeth Burton, Rodabe Amaria, Sapna Patel, Isabella Glitza, MIchael Davies, Eliza Posada, Wen-Jen Hwu, Adi Diab, Kelly Nelson, Hussein Tawbi, Michael Wong, Robert R. Jenq, Lorenzo Cohen, Carrie Daniel-MacDougall, Jennifer A. Wargo. The gut microbiome (GM) and immunotherapy response are influenced by host lifestyle factors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2838.

Meeting abstracts Cryo is an effective modality for pain palliation and local control of soft tissue and bone metastases. Cryo induces necrotic cell death, and combination cryo with anti-CTLA-4 generates potent systemic anti-tumor immune responses in preclinical models and small clinical studies.

Background Immune related adverse events (irAEs) are common side effects of checkpoint inhibitory (CPI) therapies targeting CTLA-4 and PD-1/PD-L1. Grover’s disease is an uncommon dermatologic condition with unclear pathogenesis previously reported as an irAE with ipilimumab.