Imct-07therapeutic Outcomes of Intrathecal Interleukin-2 in Metastatic Melanoma Patients With Leptomeningeal Disease (Lmd)

Glitza, Isabella C.; Rohlfs, Michelle; Bassett, Roland L.; John, Ida; Richard, Jessie; Iqbal, Masood; Bernzen, Theresa; Gerber, Donna L.; Lacey, Carol; Diab, Adi; Amaria, R.; Woodman, Scott E.; Patel, Sapna; Yee, Cassian; Hwu, Wen‐Jen; McCutcheon, Ian E.; Heimberger, Amy B.; Hwu, Patrick; Papadopoulos, Nicholas E.; Davies, Michael A.

doi:10.1093/neuonc/nov218.07

Cited by 9 publications

(11 citation statements)

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“…33 Intrathecal IL-2 has been administered safely in melanoma patients with LMD, and in some patients has resulted in clinical responses and prolonged survival. 3,34,35 A clinical trial is currently open to evaluate intrathecal treatment with ACT, with a previous case report supporting the safety and feasibility of this approach. 36 There is a critical unmet need to develop new therapeutic strategies and clinical trials for patients with LMD.…”

Section: Leptomeningeal Diseasementioning

confidence: 99%

Melanoma Brain Metastases

2017

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Metastases to the central nervous system (CNS) are one of the most common and lethal complications of metastatic melanoma. Historically, melanoma patients with CNS metastases have had dismal outcomes and very limited treatment options. However, the development of more effective targeted, immune, and radiation therapies is now leading to promising new investigations and strategies. Optimizing the development and testing of such strategies will benefit from an improved understanding of the unique molecular features of these tumors and the influence of the brain microenvironment. Accounting for unique clinical features and challenges of CNS metastases will also be critical to making significant clinical impact in patients.

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Section: Leptomeningeal Diseasementioning

confidence: 99%

Melanoma Brain Metastases

2017

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“…62,63 A recent report details a study in which IL-2 was administered intrathecally at 1-5 doses/week for four weeks, then weekly for four weeks, then every other week followed by monthly. 64 Although the data have not reached maturity, responses were seen in patients with LMM. A median survival of 9.1 months was reported with 16% of patients showing a median survival of >24 months.…”

Section: Clinical Experience With Immune Therapies In Lmmmentioning

confidence: 97%

“…A number of cases have reported complete responses to IL‐2 in patients with MBM, raising interest in its potential use in LMM . A recent report details a study in which IL‐2 was administered intrathecally at 1–5 doses/week for four weeks, then weekly for four weeks, then every other week followed by monthly . Although the data have not reached maturity, responses were seen in patients with LMM.…”

Section: Clinical Experience With Immune Therapies In Lmmmentioning

confidence: 99%

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Managing leptomeningeal melanoma metastases in the era of immune and targeted therapy

Smalley

Fedorenko

Kenchappa

et al. 2016

Intl Journal of Cancer

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Melanoma frequently metastasizes to the brain, with CNS involvement being clinically evident in ~30% of patients (as high as 75% at autopsy). In ~5% cases melanoma cells also metastasize to the leptomeninges, the sub-arachnoid space and cerebrospinal fluid (CSF). Patients with leptomeningeal melanoma metastases (LMM) have the worst prognosis and are characterized by rapid disease progression (mean survival 8-10 weeks) and a death from neurological causes. The recent years have seen tremendous progress in the development of targeted and immune therapies for melanoma that has translated into an increased survival benefit. Despite these gains, the majority of patients fail therapy and there is a suspicion that the brain and the leptomeninges are a “sanctuary” sites for melanoma cells that escape both targeted therapy and immunologic therapies. Emerging evidence suggests that 1) Cancer cells migrating to the CNS may have unique molecular properties and 2) the CNS/leptomeningeal microenvironment represents a pro-survival niche that influences therapeutic response. In this Mini-Review we will outline the clinical course of LMM development and will describe how the intracranial immune and cellular microenvironments offer both opportunities and challenges for the successful management of this disease. We will further discuss the latest data demonstrating the potential use of BRAF inhibitors and immune therapy in the management of LMM, and will review future potential therapeutic strategies for the management of this most devastating complication of advanced melanoma.

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“…One study reported on 42 participants with melanoma-associated leptomeningeal metastasis who were treated with 1 to 5 doses of intrathecal IL-2 every week for 4 weeks, followed by weekly injections for 4 weeks, and then every other week. 35 The study patients continued to receive single-injection maintenance doses every 1 to 3 months. A median survival rate of 9.1 months (range, 0.7-86.2) was reported, and 16% of study patients had an overall survival of more than 24 months.…”

Section: Intrathecal Interleukinmentioning

confidence: 99%