Thursday, February 8, 2018

Leptomeningeal Disease in melanoma - a bit of hope.

As I've said many times, "Melanoma sucks!""  and "Melanoma brain mets suck great big green hairy wizard balls!!!"  But ~ leptomeningeal disease sucks even more!!!  It is invasive, pervasive and very hard to treat.  I posted this report in 2015:  Leptomeningeal disease - a case study Intrathecal administration of tumor-infiltrating lymphocytes is well tolerated in a patients with leptomeningeal disease from metastatic melanoma: A case report.

There was also this:  Intrathecal IL2 for melanoma patients with leptomeningeal disease - long-term efficacy!!!

By the way, "intrathecal  (IT) administration" simply means that the medicine is injected into the spinal fluid via the spinal canal or the subarachnoid space - in order to place the medicine directly into the cerebrospinal fluid that our brains and spinal cord float in.  This is how anesthesia for the birth process is provided to many women via an epidural during delivery.  Similarly, IT can also be used as a route to administer pain meds for patients after surgery or with chronic back pain.  IT can also be utilized to inject antibiotics or chemotherapy for brain infections or brain tumors directly, as some medicines cannot pass through the blood brain barrier and this method of direct access gets them where they need to be. 

Sadly, in regard to metastatic melanoma patients with leptomeningeal disease (LMD), I've not had a lot of successful studies to report.  Now, there's this:

Retrospective review of metastatic melanoma patients with leptomeningeal diseasetreated with intrathecal interleukin-2. Glitza, Rohlfs, Guha-Thakurta, et al. ESMO Open. 2018 Jan 24.

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.

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.

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, positive baseline CSF cytology and concomitant use of targeted therapy 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.

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.  

These 43 patients with leptomeningeal disease were given intrathecal doses of IL-2 up to 5 times a week for 4 weeks, then every 1-3 months after that if they were still benefiting.  All of the patients developed increased intracranial pressure...which makes sense given that our body only wants a certain amount of fluid in that confined space and being given more fluid was not good.  But, the problem was managed successfully through medications and removal of extra fluid.  Average overall survival was only 7.8 months, though "1 year, 2 year, and 5 year overall survival rates were:  36%, 26%, and 13%" respectively.  So that is certainly something!!  It stands to reason that folks with neurological symptoms and/or lots of melanoma cells in their fluid when they started did less well.  Folks who were also given targeted therapy (like BRAF/MEK) simultaneously did less well....and honestly, I don't really have a reasonable explanation for that.  (Especially, since for a dear one of mine, targeted therapy was what helped her the most.)  So...I'm not sure if that is just a fluke in this report, a strange interaction of the IL-2 and the targeted therapy, or if it says something about the progression of leptomeningeal disease in BRAF positive patients.  I don't know. 

Still, this is the most positive outcomes I've seen for patients with LMD in a while.  Hang in there dear ones!  Hang in there!!! - c

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