372MO - Melanoma leptomeningeal metastases: A European multicenter cohort

Background

Among solid cancers, melanoma may have the greatest affinity for the central nervous system. The development of systemic treatment approaches and their combination with local therapy have improved the prognosis of melanoma patients with brain metastases. However, only few contemporary cohorts of melanoma patients with leptomeningeal metastases (LM) have been reported.

Methods

We retrospectively reviewed files of 51 melanoma patients with newly diagnosed LM from 7 European centers. The clinical description, brain or cerebrospinal MRI, and CSF data at diagnosis had to be available. EANO ESMO criteria for LM were retrospectively applied.

Results

At LM diagnosis, median age was 60 years (interquartile range - IQR: 44-66), median Karnofsky performance score (KPS) was 70 (IQR: 60-90%). Clinical signs were noted in 44 patients (86%). CSF tumor cells were noted in 38 patiens (74%). The most frequent MRI presentation was linear disease (EANO ESMO type A) (n=21, 41%), then combined linear and nodular disease (EANO ESMO type C) (n=16, 31%). The diagnosis was confirmed for 39 patients (76%), probable for 10 (20%), possible in 2 (4%). A BRAF mutation was noted in 38 tumors (76%). Systemic treatment was administered in 23 patients (51%), including targeted therapy in 13 (56%) and immunotherapy in 3 (13%). Patients with BRAF-mutated tumors received systemic treatment in 22 cases (58%), including targeted therapy in 13 patients (59%). Intrathecal treatment was given in 23 patients (45%). Whole brain radiotherapy was used in 16 patients (31%), 33 patients (65%) had no brain radiotherapy. The combination of systemic and intrathecal treatment (n=13, 25%) was the most commonly used combination. No specific treatment was given to 11 patients (22%). Median OS for the whole cohort was 1.7 months (IQR: 0.9-5.2). Median OS was 1.5 months (0.8-4.3) in type I LM versus 2.2 months (1.5-8.1) in type II LM; 1.9 months (IQR: 0.9-4.5 months) in BRAF mutated tumors versus 4.6 (IQR:1.4-8.6) in the BRAF non-mutated tumors; and 1.4 (IQR: 0.5-1.6) without versus 2.9 months (IQR: 1-6) with treatment.

Conclusions

The prognosis of LM in melanoma patients remains poor despite novel systemic treatment options. New therapeutic approaches are urgently needed in this population.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

University Hospital Zurich (2017-02098).

Funding

Has not received any funding.

Disclosure

E. Le Rhun: Advisory/Consultancy: Tocagen; Advisory/Consultancy, Travel/Accommodation/Expenses: AbbVie; Advisory/Consultancy: Daiichi Sankyo. K. Seystahl: Advisory/Consultancy: Roche. M.J. van den Bent: Advisory/Consultancy: Bayer; Advisory/Consultancy: Carthera; Advisory/Consultancy: Nerviano; Advisory/Consultancy: Agios; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Amgen; Advisory/Consultancy: Karyopharm; Advisory/Consultancy: Genenta. M. Preusser: Advisory/Consultancy: Bayer; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Roche; Advisory/Consultancy: BMJ Journals; Advisory/Consultancy: MedMedia; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Lilly; Advisory/Consultancy: Medahead; Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy: Sanofi; Advisory/Consultancy, Research grant/Funding (institution): Merck, Sharp & Dohme; Advisory/Consultancy: Tocagen; Advisory/Consultancy: Novartis; Advisory/Consultancy: Germon Lehrman Group; Advisory/Consultancy: GMC Contrast; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Mundipharma. F. Wolpert: Travel/Accommodation/Expenses: Roche. U. Herrlinger: Advisory/Consultancy: Medac; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Novocure; Advisory/Consultancy: Novartis; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Noxxon; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Bayer; Advisory/Consultancy: Janssen; Advisory/Consultancy: Karyopharm. L. Mortier: Travel/Accommodation/Expenses: Roche/Genentech; Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): MSD Oncology; Research grant/Funding (institution): Pierre Fabre. R. Dummer: Advisory/Consultancy: Novartis; Advisory/Consultancy: Merck Sharp & Dhome (MSD); Advisory/Consultancy: Bristol-Myers Squibb (BMS); Advisory/Consultancy: Roche; Advisory/Consultancy: Amgen; Advisory/Consultancy: Takeda; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Sun Pharma; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Catalym; Advisory/Consultancy: Second Genome; Advisory/Consultancy: Regeneron; Advisory/Consultancy: Alligator. M. Weller: Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Adastra; Research grant/Funding (institution): Dracen; Advisory/Consultancy, Research grant/Funding (institution): Merck, Sharp & Dohme; Advisory/Consultancy, Research grant/Funding (institution): Merck (EMD); Advisory/Consultancy, Research grant/Funding (institution): Novocure; Advisory/Consultancy: Orbus; Advisory/Consultancy: Basilea; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Celgene; Advisory/Consultancy: Medac; Advisory/Consultancy: Roche; Advisory/Consultancy: Tocagen. All other authors have declared no conflicts of interest.