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Retrospective review of metastatic melanoma patients with leptomeningeal disease treated with intrathecal interleukin-2
  1. Isabella C Glitza1,
  2. Michelle Rohlfs1,
  3. Nandita Guha-Thakurta2,
  4. Roland L Bassett Jr3,
  5. Chantale Bernatchez1,
  6. Adi Diab1,
  7. Scott E Woodman1,
  8. Cassian Yee1,
  9. Rodabe N Amaria1,
  10. Sapna P Patel1,
  11. Hussein Tawbi1,
  12. Michael Wong1,
  13. Wen-Jen Hwu1,
  14. Patrick Hwu1,
  15. Amy Heimberger4,
  16. Ian E McCutcheon4,
  17. Nicholas Papadopoulos1,
  18. Michael A Davies1
  1. 1 Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  2. 2 Department of Diagnostic Radiology/ Neuro Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  3. 3 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  4. 4 Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  1. Correspondence to Dr Isabella C Glitza; icglitza{at}mdanderson.org

Abstract

Objectives Metastatic melanoma patients with leptomeningeal disease (LMD) have an extremely poor prognosis, with a median survival measured in weeks, and few treatment options. Outcomes of a retrospective cohort of patients with LMD that were treated with intrathecal interleukin-2 (IT IL-2) were reviewed to assess the long-term efficacy of this therapy.

Methods The records of metastatic melanoma patients with LMD who were treated with IT IL-2 from 2006 to 2014 in a Compassionate Investigational New Drug study were reviewed. IL-2 (1.2 mIU) was administered intrathecally via Ommaya reservoir up to five times per week in the inpatient setting for 4 weeks; patients with good tolerance and clinical benefit received maintenance IT IL-2 every 1–3 months thereafter.

Results The cohort included 43 patients. The median age of the patients was 47 years (range 18–71), and 32 (74%) were male. 23 patients (53%) had positive cerebrospinal fluid (CSF) cytology and radiographic evidence of LMD, 8 (19%) had positive CSF cytology only, 9 (21%) had radiographic evidence only and 3 (7%) were diagnosed based on pathology review after craniotomy. The median overall survival (OS) from initiation of IT IL-2 was 7.8 months (range, 0.4–90.8 months), with 1-year, 2-year and 5-year OS rates of 36%, 26% and 13%. The presence of neurological symptoms (HR 2.1, P=0.03), positive baseline CSF cytology (HR 4.1, P=0.001) and concomitant use of targeted therapy (HR 3.0, P=0.02) was associated with shorter OS on univariate analysis. All patients developed symptoms due to increased intracranial pressure which was managed with supportive medications and/or CSF removal, and there were no treatment-related deaths.

Conclusion These results demonstrate that despite their historically dismal prognosis a subset of metastatic melanoma patients with LMD treated with IT IL-2 can achieve long-term survival, but these data need to be verified in a prospective trial setting.

  • intrathecal therapy
  • interleukin-2
  • leptomeningeal disease
  • melanoma

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Footnotes

  • Contributors All authors have contributed to this article.

  • Funding Analyses for this study were supported in part by the Cancer Center Support Grant (NCI Grant P30 CA016672) and MAD acknowledges support from 1R01CA187076-02 and 5R01CA154710-04.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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