TY - JOUR
T1 - Retrospective review of metastatic melanoma patients with leptomeningeal disease treated with intrathecal interleukin-2
AU - Glitza, Isabella C.
AU - Rohlfs, Michelle
AU - Guha-Thakurta, Nandita
AU - Bassett, Roland L.
AU - Bernatchez, Chantale
AU - Diab, Adi
AU - Woodman, Scott E.
AU - Yee, Cassian
AU - Amaria, Rodabe N.
AU - Patel, Sapna P.
AU - Tawbi, Hussein
AU - Wong, Michael
AU - Hwu, Wen Jen
AU - Hwu, Patrick
AU - Heimberger, Amy
AU - McCutcheon, Ian E.
AU - Papadopoulos, Nicholas
AU - Davies, Michael A.
N1 - Funding Information:
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.
Funding Information:
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.
Publisher Copyright:
© European Society for Medical Oncology (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - interleukin-2
KW - intrathecal therapy
KW - leptomeningeal disease
KW - melanoma
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U2 - 10.1136/esmoopen-2017-000283
DO - 10.1136/esmoopen-2017-000283
M3 - Article
C2 - 29387478
AN - SCOPUS:85051538762
SN - 2059-7029
VL - 3
JO - ESMO Open
JF - ESMO Open
IS - 1
M1 - e000283
ER -