[GregA]

Multiple myeloma, multiple sclerosis, and Tysabri

by GregA on Sun Feb 08, 2015 6:30 pm

Hi,

I was diagnosed with multiple myeloma in November of last year after having a tumor removed from my T-1 vertebra. Also, I have multiple sclerosis (25 Years). Since 2007 I have been re­ceiv­ing Tysabri (natalizumab) infusions once a month for my multiple sclerosis. Because of my recent diag­nosis, I have been taken off Tysabri. However, I am considering resuming my treatment be­cause I don’t want my MS to get worse and, according to what I read in the past, Tysabri may help with my multiple myeloma.

About the time I started Tysabri, there was news of it being used as a potential treatment for multiple myeloma. A case regarding Frederick Baron, who was near death from multiple myeloma, received a lot of atten­tion due to his notoriety and the fact there was a clinical trial was underway. According to news­paper articles, the Mayo Clinic discovered that Baron's multiple myeloma responded surprisingly well in the lab to Tysabri. Also, according to reports, he received one dose, to which he showed some improvement, before his death.

The Phase I/II trial was conducted by Biogen Idec in 2008 (ClinicalTrials.gov Identifier: NCT00675428) to study Tysabri in relapsed / refractory multiple myeloma. Unfortunately, the study was terminated due to low enrollment.

More recently, a report published in the British Journal of Haematology evaluated the use of Tysabri with Velcade to improve patient outcome (see reference and abstract below).

My question is: Does anyone know of any studies of Tysabri being used as a treatment for multiple myeloma or of anyone with multiple myeloma taking Tysabri.

Currently, I am discussing this with my oncologist and neurologist.

Thanks in advance for any info.
Greg

---

K Podar et al, "The selective adhesion molecule inhibitor natalizumab decreases multiple myeloma cell growth in the bone marrow microenvironment: therapeutic implications," British Journal of Haematology, November 2011 (full study)

Abstract:

Recent advances regarding the introduction of anti-adhesion strategies as a novel therapeutic concept in oncology hold great promise. Here we evaluated the therapeutic potential of the new-in-class-molecule selective-adhesion-molecule (SAM) inhibitor natalizumab, a re­com­bi­nant humanized IgG4 monoclonal antibody, which binds integrin-α4, in multiple myeloma (multiple myeloma).

Natalizumab, but not a control antibody, inhibited adhesion of multiple myeloma cells to non-cellular and cellular components of the microenvironment as well as disrupted the binding of already ad­herent multiple myeloma cells. Consequently, natalizumab blocked both the proliferative effect of MM-bone marrow (BM) stromal cell interaction on tumour cells, and vascular endothelial growth factor (VEGF)-induced angiogenesis in the BM milieu. Moreover, natalizumab also blocked VEGF- and insulin-like growth factor 1 (IGF-1)-induced signalling sequelae triggering multiple myeloma cell mi­gra­tion.

In agreement with our in vitro results, natalizumab inhibited tumour growth, VEGF secretion, and angiogenesis in a human severe combined immunodeficiency murine model of human multiple myeloma in the human BM microenvironment. Importantly, natalizumab not only blocked tumour cell adhesion, but also chemosensitized multiple myeloma cells to bortezomib, in an in vitro therapeutically rep­re­sentative human MM-stroma cell co-culture system model.

Our data therefore provide the rationale for the clinical evaluation of natalizumab, preferably in combination with novel agents (e.g. bortezomib) to enhance multiple myeloma cytotoxicity and improve patient outcome.

[Multibilly]

Re: Multiple myeloma, multiple sclerosis, and Tysabri

by Multibilly on Sun Feb 08, 2015 9:42 pm

Hi Greg,

To be clear, are you simply hoping to kill two birds with one stone (this is, treat two different diseases with one monoclonal antibody)?

I am sure you probably already know this, but there are several current trials for other monoclonal antibodies that have been developed specifically for the cellular markers associated with multiple myeloma - and these are showing some great promise.

[Ian]

Re: Multiple myeloma, multiple sclerosis, and Tysabri

by Ian on Mon Feb 09, 2015 3:13 am

Hi Greg,

I poked around a bit and can't seem to find anything else about Tysabri as a myeloma therapy beyond the paper that you mention.

One thing I did find out, however, that might be relevant to what you decide to do is that Tysabri is a stem cell mobilizer -- it causes the sort of stem cells that are collected for stem cell transplantation (CD34+ cells) to leave the bone marrow and be present in higher concentrations in the blood than would normally be the case. In addition, the stem cells that it mobilizes out into the blood seem to be less inclined to re-implant in the bone marrow than other stem cells.

You can find several papers on this subject by googling "natalizumab cd4+". Most of the research on the subject seems to have come out of a group in Germany. See, for example, this abstract:

https://ash.confex.com/ash/2010/webprogram/Paper31563.html

I would think that this is something you would want to discuss with your physicians. For example, you might ask whether Tysabri's tendency to mobilize stem cells into the blood might increase the likelihood that you might develop extramedullary disease (myeloma tumors / plasmacytomas outside the bone). As you probably know, extramedullary disease / EMD is not something doctors generally like to find in their myeloma patients, although that's typically because EMD is a sign of a more aggressive myeloma clone being present, which may not hold true in the case of EMD sparked by treatment with Tysabri.

Let us know if you find out anything more on this topic. I'd be interested to hear what you learn.

[GregA]

Re: Multiple myeloma, multiple sclerosis, and Tysabri

by GregA on Mon Feb 09, 2015 12:32 pm

Thanks Ian.

I'll discuss this with my doc.

[Bar-none]

Re: Multiple myeloma, multiple sclerosis, and Tysabri

by Bar-none on Sun Feb 15, 2015 10:27 am

Greg, My MS doc would not start Tysabri after I was diagnosed with multiple myeloma. He wanted me to focus on my multiple myeloma treatment and not complicate my situation.

I would be curious to know if your doc is aware of any data regarding Tysabri with Revlimid.

Thanks, BN

[Bar-none]

Re: Multiple myeloma, multiple sclerosis, and Tysabri

by Bar-none on Thu Oct 29, 2015 10:51 am

Greg, how are you doing? Have you gone back on Tysabri? Can you give any updates?

Hope all is well.

Best! BN

[Bar-none]

Re: Multiple myeloma, multiple sclerosis, and Tysabri

by Bar-none on Sat Feb 13, 2016 12:17 pm

Hi,

After doing my due diligence with my pharmacist, neurologist, and myeloma specialist, a few weeks ago I was started on Copaxone (glatiramer acetate injection) 40 mg subq 3 times a week.

We settled on Copaxone since it was apparently a lower impact on the immune system, and vital organs than other multiple sclerosis disease modifiers.

Subjectively I do feel that it is helping my multiple sclerosis symptoms. I have had a slight improvement in sensation in various areas. This was quite surprising to me until I located a study on mice that indicated some possible evidence of remyelination signatures.

Hope this helps and I would really like to hear from other dual multiple sclerosis and myeloma patients with experiences of any treatments.

Best! BN