Background Breast cancer-related leptomeningeal disease (BC-LMD) is a dire diagnosis for 5–8% of patients with breast cancer (BC). We conducted a retrospective review of BC-LMD patients diagnosed at Moffitt Cancer Center (MCC) from 2011–2020, to determine the changing incidence of BC-LMD, which factors impact progression of BC CNS metastasis to BC-LMD, and which factors affect OS for patients with BC-LMD Methods Patients with BC and brain/spinal metastatic disease were identified. For those who eventually developed BC-LMD, we used Kaplan-Meier survival curve, log-rank test, univariable, and multivariate Cox proportional hazards regression model to identify factors affecting time from CNS metastasis to BC-LMD and OS. Results 128 cases of BC-LMD were identified. The proportion of BC-LMD to total BC patients was higher between 2016–2020 when compared to 2011–2015. Patients with HR + or HER2 + BC experienced longer times between CNS metastasis and LMD than patients with triple-negative breast cancer (TNBC). Systemic therapy and whole-brain radiation therapy (WBRT) prolonged progression to LMD in all patients. Hormone therapy in patients with HR + BC delayed BC-CNS metastasis to LMD progression. Lapatinib delayed progression to LMD in patients with HER2 + BC. Patients with TNBC-LMD had shorter OS compared to those with HR + and HER2 + BC-LMD. Systemic therapy, intrathecal (IT) therapy, and WBRT prolonged survival for all patients. Lapatinib and trastuzumab improved OS in patients with HER2 + BC-LMD. Conclusions Increasing rates of BC-LMD provide treatment challenges and opportunities for clinical trials. Trials testing lapatinib and/or similar tyrosine kinase inhibitors, IT therapies, and combination treatments are urgently needed.

Melanoma is third most common cancer to metastasize to the leptomeningeal space and confers a dismal prognosis. We retrospectively identified 87 cases of melanoma related leptomeningeal disease (M-LMD) diagnosed between 2011-2020 at Moffitt Cancer Center. The average age at diagnosis was 54 years (range 28-93 years) with a male predominance (50 men vs 36 women). There was a significant increase in median overall survival (OS) for patients with BRAF V600E mutation, but only if they were treated with combined BRAF/MEK inhibitors after diagnosis of LMD (5.54 months vs 1.39 months; p < 0.01). Immune checkpoint inhibitors also associated with a small but significant increase in OS when given after diagnosis of M-LMD (2.73 months vs 1.38mths; p < 0.01). There was no association between OS and gender (p > 0.05). The current data supports use of BRAF/MEK inhibitors for treatment of BRAF V600E mutated M-LMD. More work is needed to improve OS for these patients and patients without a targetable mutation and M-LMD.

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Central nervous system (CNS) manifestation of chronic graft versus host disease (cGVHD) is a rare, difficult to diagnose phenomenon that can follow allogeneic hematopoietic stem cell transplantation (HSCT). CNS-cGVHD typically onsets 2-31 months post-transplant, involves diffuse infiltration of inflammatory cells, demyelination, and cerebral vasculitis, and is associated with an extremely poor prognosis. We present a case of a 37-year-old man who developed seizures, myopathy, bilateral upper and lower extremity weakness, confusion, and irritability almost 2 years after HSCT for acute myeloid leukemia (AML). CNS-cGVHD diagnosis was confidently determined via magnetic resonance imaging (MRI) demonstrating enhanced focal white matter lesions, cerebrospinal fluid (CSF) studies demonstrating elevated globulin (12.7 mg/dL; normal range: 0-6 mg/dL) and elevated immunoglobulin G (IgG) synthesis rate (13.9 mg/d; normal range: ≤ 8 mg/d), and a right brain biopsy demonstrating encephalitis, perivascular inflammation, microglial activation, and gliosis with predominately intramural and perivascular CD3+ T-cells, CD4+ and CD8+ cells. Complete resolution of neurological symptoms, including seizures, was achieved with a combination of steroids, ibrutinib, intravenous immunoglobulin (IVIG), and anti-seizure medications. Improvements to CNS-cGVHD was further indicated by normalized MRI studies without abnormal enhancements and improved CSF studies with reduction in globulin levels (11.3 mg/dL) and complete normalization of IgG synthesis rate (≤ 0 mg/d). It is imperative that CNS-cGVHD be considered in patients that present with neurological signs post-transplant. An early, confident diagnosis generates prompt intervention and as demonstrated, can lead to complete resolution of neurological symptoms.

e21548 Background: Leptomeningeal disease (LMD) is characterized by tumor metastasis to the membranes and cerebrospinal fluid (CSF) surrounding the brain and spinal cord. This devastating complication confers a poor overall survival (OS) measured in weeks for untreated patients. Melanoma has one of the highest rates of dissemination to the leptomeninges. The advances in targeted and immune therapies have revolutionized OS for patients with melanoma systemic metastases and there is a growing number of individual case reports showing clinical responses to these agents in patients with melanoma-LMD (M-LMD) . However, few studies have examined the association between these and other therapies with the OS of a large cohort of melanoma-LMD (M-LMD) patients. Methods: M-LMD patients treated at Moffitt Cancer Center between 2011 and 2020 were retrospectively identified. M-LMD diagnosis was confirmed radiographically via magnetic resonance imaging (MRI) and/or positive CSF cytology indicating the presence of malignant cells. Demographic data and pre/post LMD diagnosis treatment data were collected and analyzed using the Kaplan-Meier method to determine factors that improve OS. Results: 86 M-LMD patients were identified. 50 were male and 36 were female, but patient gender did not have an impact on OS. 53 patients were diagnosed via MRI only and 33 patients had positive CSF cytology confirming M-LMD diagnosis. 34 patients did not receive any treatment post-LMD diagnosis and had a median OS of 3.72 weeks, while 52 patients receiving treatment (i.e. systemic, intrathecal [IT], and/or whole brain radiation therapy [WBRT]) had a median OS of 10.80 weeks (p < 0.0001). More specifically, 30 patients receiving targeted BRAF/MEKi treatment had an 18.8 week median OS compared to 6.68 weeks for the 56 patients who did not receive such treatments (p = 0.0015). Furthermore, 44 patients received immune therapy and had a median OS of 12.00 weeks compared to 5.88 weeks for those who did not (p = 0.002). The 16 Patients that received IT chemotherapy had a prolonged median OS when compared to the 70 patients who did not (9.72 weeks vs 4.72 weeks, p = 0.009). Furthermore, WBRT also improved median OS in the 22 patients that received the therapy (15.72 weeks vs 7.88 weeks, p = 0.0007). The 36 patients that received BRAF/MEKi treatment prior to their LMD diagnosis had a slightly shorter OS (7.00 weeks) compared to the 46 patients that did not receive such treatment beforehand (10.80 weeks, p = 0.005). Conclusions: The current data supports the use of systemic, IT, and radiation therapies to prolong OS for M-LMD patients; however, the OS for these patients remains grim despite advances in such therapies. Further research is necessary to understand the pathophysiology of LMD, and new clinical trials are urgently needed to identify novel therapies that improve M-LMD prognosis.