Impact of New Systemic Treatment and Radiotherapy in Melanoma Patients with Leptomeningeal Metastases

Pauline Tétu; Lila Sirven-Villaros; Stefania Cuzzubbo; Renata Ursu; Barouyr Baroudjian; Julie Delyon; François Nataf; Constance De Margerie-Mellon; Clara Allayous; Wendy Lefevre; Antoine F Carpentier; Céleste Lebbé

doi:10.3390/cancers12092635

Impact of New Systemic Treatment and Radiotherapy in Melanoma Patients with Leptomeningeal Metastases

Cancers (Basel). 2020 Sep 16;12(9):2635. doi: 10.3390/cancers12092635.

Authors

Pauline Tétu^{1

2}, Lila Sirven-Villaros³, Stefania Cuzzubbo³, Renata Ursu³, Barouyr Baroudjian^{1

2}, Julie Delyon^{1

2}, François Nataf⁴, Constance De Margerie-Mellon^{5

6}, Clara Allayous^{1

2}, Wendy Lefevre^{1

2}, Antoine F Carpentier³, Céleste Lebbé^{1

2}

Affiliations

¹ Assitance Publique des Hôpitaux de Paris Dermatology, Department of Dermatology, Hôpital Saint-Louis, 75010 Paris, France.
² INSERM U976, Paris 7 Diderot University, 75475 Paris, France.
³ Service de Neurologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, 75010 Paris, France.
⁴ Department of Neurosurgery, Groupement Hospitalo-Universitaire-PARIS, Hôpital Sainte-Anne Paris, 75014 Paris, France.
⁵ INSERM UMR 1149, Université de Paris, F-75018 Paris, France.
⁶ Radiology Department, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, F-75010 Paris, France.

Abstract

Importance: Few data are available on patients with leptomeningeal disease (LM) from melanoma treated with new systemic therapies.

Objective: To gain a better understanding of patients, disease characteristics, and therapeutic interventions in melanoma patients with LM in the era of new systemic treatment.

Design: Clinical characteristics, treatments, and survival of melanoma patients diagnosed with LM, isolated or associated with brain metastases, were collected. The Cox regression model assessed the influence of patient and melanoma characteristics on survival.

Setting: Monocentric, retrospective, real-life cohort of patients with LM from melanoma.

Participants: All patients followed up at Saint-Louis University Hospital and diagnosed with LM between December 2013 and February 2020 were included. For each patient identified, a central review by dermato-oncologist and neuro-oncologist experts was performed to confirm the diagnosis of LM.

Exposure: Impact of new systemic therapies and radiotherapy.

Results: Among the 452 advanced melanoma patients followed at St Louis Hospital between 2013 and 2020, 41 patients with LM from melanoma were identified. Among them, 29 patients with a diagnosis of LM "confirmed" or "probable" after central neuro-oncologists reviewing were included. Nineteen patients had known melanoma brain metastases at LM diagnosis. Among the 27 patients treated with systemic therapy, 17 patients were treated with immunotherapy, 5 patients received targeted therapy, 1 was treated with chemotherapy, and 4 patients were treated with anti-PD-1 in combination with BRAF inhibitor. The median overall survival (OS) from LM diagnosis was 5.1 months. Median OS was 7.1 months for the 9 patients receiving systemic therapy combined with radiotherapy, and 3.2 months for the 20 patients not receiving combined radiotherapy. Elevated serum lactate dehydrogenase (LDH) (HR 1.44, 95% CI 1.09-1.90, p < 0.01) and presence of neurological symptoms at LM diagnosis (HR 2.96, 95% CI 1.25-6.99, p = 0.01) were associated with poor survival. At the time of data analysis, five patients were still alive with a median follow-up of 47.4 months and had persistent complete response.

Conclusion: Targeted therapy and immunotherapy are promising new treatment options in LM from melanoma that can increase overall survival, and may induce long lasting remission in some patients.

Keywords: immunotherapy; leptomeningeal melanoma; radiotherapy; survival; targeted therapy.