Brain Tumor Res Treat.  2021 Oct;9(2):100-105. 10.14791/btrt.2021.9.e19.

Lorlatinib Therapy for Rapid and Dramatic Control of Brain and Spinal Leptomeningeal Metastases From ALK-Positive Lung Adenocarcinoma

Affiliations
  • 1Departments of Neurosurgery, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea
  • 2Departments of Pulmonology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea
  • 3Departments of Pathology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea

Abstract

We report a patient with severe neurological deterioration due to leptomeningeal metastases involving brain and spinal cord from anaplastic lymphoma kinase (ALK)-positive lung adenocarcinoma, managed rapidly and successfully with lorlatinib therapy. A 48-year-old male patient presented with acute mental deterioration, severe headache, and weakness of both legs. The patient’s previous medical history included cerebral metastases from ALK-positive lung adenocarcinoma, which had been successfully managed via whole brain radiation therapy and gamma knife radiosurgery one year and three months before, respectively. Physical examination revealed neck stiffness and paraparesis with motor grade I. Gadolinium-enhanced brain MRI showed newly developed leptomeningeal enhancement along cerebellar folia, and whole spine MRI revealed similar leptomeningeal metastasis along the whole spinal axis. Lorlatinib was started orally with a dose of 100 mg/day. The patient showed rapid clinical improvement after one week. The patient was alert and the headache disappeared, while the paraparesis improved to normal ambulatory status. Two months of lorlatinib treatment resulted in almost complete disappearance of previous leptomeningeal enhancement of brain and spinal cord, and absence of newly developed metastatic lesions in the central nervous system, based on MRI results. The patient had been regularly followed with ongoing lorlatinib therapy for 5 months without any systemic complications or neurological abnormality. Conclusively, lorlatinib could be a rapid and effective treatment for patients with central nervous system leptomeningeal metastases arising from ALK-positive lung cancer.

Keyword

Anaplastic lymphoma kinase; Brain metastases; Leptomeningeal carcinomatosis; Lorlatinib; Magnetic resonance imaging

Figure

  • Fig. 1 Gadolinium-enhanced MRIs show severe brain metastases (A-C), which were well controlled (D-F) after two months of alectinib therapy and whole brain radiation therapy.

  • Fig. 2 The cancer cells show infiltrative atypical glands with mucinous differentiation (H&E, ×100) (A), and anaplastic lymphoma kinase fluorescence in situ hybridization shows many isolated red signals and spilt signals (×200) (B).

  • Fig. 3 Gadolinium-enhanced brain MRIs show newly developed leptomeningeal enhancement along both cerebellar folia.

  • Fig. 4 The spine MRIs show multiple intramedullary and leptomenigeal metastases along the whole spinal axis.

  • Fig. 5 The brain MRIs show improvement in leptomeningeal metastasis two months after lorlatinib treatment.

  • Fig. 6 The spine MRIs show improvement in leptomeningeal metastasis along the whole spinal axis three months after lorlatinib treatment.


Reference

1. Gafer H, de Waard Q, Compter A, van den Heuvel M. Rapid regression of neurological symptoms in patients with metastasised ALK+ lung cancer who are treated with lorlatinib: a report of two cases. BMJ Case Rep. 2019; 12:e227299.
2. Cheng H, Perez-Soler R. Leptomeningeal metastases in non-small-cell lung cancer. Lancet Oncol. 2018; 19:e43–e55. PMID: 29304362.
3. Akamine T, Toyokawa G, Tagawa T, Seto T. Spotlight on lorlatinib and its potential in the treatment of NSCLC: the evidence to date. Onco Targets Ther. 2018; 11:5093–5101. PMID: 30174447.
4. Shaw AT, Bauer TM, Felip E, et al. Clinical activity and safety of PF-06463922 from a dose escalation study in patients with advanced ALK+ or ROS1+ NSCLC. J Clin Oncol. 2015; 33:8018.
5. Solomon BJ, Besse B, Bauer TM, et al. Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. Lancet Oncol. 2018; 19:1654–1667. PMID: 30413378.
6. Remon J, Le Rhun E, Besse B. Leptomeningeal carcinomatosis in non-small cell lung cancer patients: a continuing challenge in the personalized treatment era. Cancer Treat Rev. 2017; 53:128–137. PMID: 28110254.
7. Le Rhun E, Galanis E. Leptomeningeal metastases of solid cancer. Curr Opin Neurol. 2016; 29:797–805. PMID: 27661208.
8. Li YS, Jiang BY, Yang JJ, et al. Leptomeningeal metastases in patients with NSCLC with EGFR mutations. J Thorac Oncol. 2016; 11:1962–1969. PMID: 27539328.
9. Hochmair MJ, Schwab S, Prosch H. Complete remission of intrathecal metastases with lorlatinib therapy in a heavily pretreated ALK-positive lung cancer patient. Anticancer Drugs. 2017; 28:928–930. PMID: 28628492.
10. Johnson TW, Richardson PF, Bailey S, et al. Discovery of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a macrocyclic inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) with preclinical brain exposure and broad-spectrum potency against ALK-resistant mutations. J Med Chem. 2014; 57:4720–4744. PMID: 24819116.
Full Text Links
  • BTRT
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr