[Giorgi Galas]

Extramedullary plasmacytomas in eyes, spinal nerves

by Giorgi Galas on Mon Mar 30, 2015 4:06 pm

Hi all,

This is my first post on this extensive and interesting forum. I decided to try to find out patients experiences in struggling with myeloma. I have learned that my doctors attempts to acquire lacking information from their international colleagues does not always work, so why not try myself from a first hand source?

I'm from Eastern Europe – Tbilisi, Georgia. Here, the national health care system is not well-developed, and we suffer from lack of expertise and experience in fighting this disease, es­pecially if it develops very strange characters.

It is all about my young wife. She is 35. A year and a half after she gave birth to our twin ladies, she was diagnosed with multiple myeloma in 2013. We went to Berlin, Germany, where she undertook a chemotherapy of Velcade-dexamethasone-cyclophosphamide [VCD, CyBorD], followed by a stem cell transplant. Remission was achieved.

In spring 2014, she noticed gray spots in her vision. It was extremely difficult to diagnose what was going on in her eyes. German doctors requested information from their international part­ners. They sent the case materials to California, but no one had an idea what was going on there: a fascinating case, as they put it (the file is attached).

Finally, after a biopsy, it appeared an extramedullary plasmacytoma had formed on the retina that damaged vision in one eye (see the image below). We hurried to save the second eye. We managed. The Avastin (bevacizumab) injection worked, but it was described as wonder medi­cine by German doctors.

the eye and retina

000549-20140423@122230-R2 (1).jpg (9.96 KiB) Viewed 2182 times

The Avastin works for a while – we still inject it once or twice in a quarter – and it stops pro­gression.

In this spring (spring appears to be a challenging season for myeloma), MRI revealed two neo­plasms on the "cauda equina" (collection of nerves in the lower back). We are on our way to plan a treatment. Unfortunately, no one has seen such development of myeloma and it seems that we are experimenting. We have planned to undertake local irradiation of those two spots of neoplasms. Here is an image of the new tumors:

Tumors on Cauda Equina V2.png (254.79 KiB) Viewed 2110 times

I am very curious if anyone has had similar types of extramedullary tumors. I would be very thankful if one could share his / her experience and knowledge. Unfortunately, we cannot afford to travel to U.S. for treatment, and the limited accessibility to quality treatment and professional knowledge affects our life.

I'm looking forward to hearing from you. If anyone is interested in any further details, I'd love to share if it helps someone in this troublesome health problem.

Thank you very much.

[Beacon Staff]

Re: Extramedullary plasmacytomas in eyes, spinal nerves

by Beacon Staff on Tue Mar 31, 2015 8:07 am

Just an update for everyone about Giorgi's posting directly above.

We have updated it a bit based on some private messaging with him to clarify the location of the new extramedullary tumors his wife has developed. The update includes a new image that gives a better sense of where the tumors are located.

[NStewart]

Re: Extramedullary plasmacytomas in eyes, spinal nerves

by NStewart on Tue Mar 31, 2015 11:58 am

Giorgi-

My heart goes out to your wife, you, and your young children. What a curious and difficult form of myeloma that your wife seems to have. Do you know where your wife's oncologists sent her information besides to California? I would think that maybe it should go to Dr. Palumbo's group in Italy and the group in France (I can't remember the name of the doctor).

As a retired physical therapist in the States who specialized in treating people with cancer, I treated a woman a few years ago with metastatic lung cancer who had developed tumors in her eyes. She received Avastin injections in her eyes every other month to keep those tumors under control. She was also receiving Avastin infusions for her lung cancer every month. At the time, the Avastin was controlling the spread of the cancer any further and maintained her ability to see. It's been about 4 years since I have had any contact with the woman, so I don't know how she has done long term. But, the Avastin injections don't seem to be too, too uncommon for eye tumors. One of the things that Avastin does is stop the development of blood vessels to the tumors.

I hope that you get some responses to your request for help. I wish that I had more information to give you.

Nancy in Phila

[Dr. Ken Shain]

Re: Extramedullary plasmacytomas in eyes, spinal nerves

by Dr. Ken Shain on Wed Apr 01, 2015 12:53 am

I am very sorry to hear about your wife's relapse. Relapse is never easy. Made even more difficult by the presentation with multiple extramedullary plasmacytomas.

Extramedullary plasmacytomas are not a new phenomenon in multiple myeloma. As some on the Beacon can likely attest, individuals can present with 1 or more extramedullary plasma­cytomas. They can form essentially anywhere. I have seen them in the brain, compromising cranial nerves (causing visual and motor issues), on the outside of a patient's eye, in the GI tract, in the skin, and a number of other places.

However, I will say that there appears to be an increase in the incidence of extramedullary plasmacytomas. This is likely, at least in part, the consequence of the success of our current therapy. It appears that, at least anecdotally, because our therapies today, which are usually based on the newer myeloma agents (Velcade, Revlimid, or the other IMIDS), are so effective at targeting multiple myeloma within the bone marrow – and have suppressed the myeloma so effectively there – that we see relapse in extramedullary areas.

The extramedullary plasmacytomas are a product of our success, so to speak. As people live longer, the multiple myeloma has a chance to change and evolve, going to non-bone marrow sites. I have yet to see a convincing article, however, demonstrating that this is what is happening, so it remains speculative on my part.

For therapy:

If possible, radiation is a critical component of therapy for extramedullary plasma­cytomas. They are generally very radiosensitive (as are essentially all plasmacytomas).

For systemic therapy, I would also recommend combined therapy with Velcade (or other proteasome inhibitors), Cytoxan (cyclophosphamide), and dex. The key to me is combining a proteasome inhibitor with a more traditional chemotherapy – Cytoxan, bendamustine (Treanda), Doxil (doxorubicin liposomal, Caelyx), or melphalan – thus, targeting the the non-marrow space.

Another combination to consider is Pomalyst (pomalidomide, Imnovid), Cytoxan, and dex.

Also, depending on your wife's overall health, and given that the extramedullary plasma­cytomas in her case involve the central nervous system, infusional therapy with DCEP or VTD-PACE, and intrathecal chemotherapy (chemotherapy directly into the cerebrospinal fluid that baths the brain and spinal cord), may also be something to consider. Note these are very toxic and aggressive treatment regimens, made up of a combination of traditional chemotherapies. So the choice must be made carefully, and with the entire picture in mind, so it is important to establish the true goals of therapy.

[DCEP = dexamethasone, cyclophosphamide, etoposide, and cisplatin; VTD-PACE = Velcade, thalidomide, dexamethasone - cisplatin, doxorubicin, cyclophosphamide, etoposide.]

[Giorgi Galas]

Re: Extramedullary plasmacytomas in eyes, spinal nerves

by Giorgi Galas on Wed Apr 01, 2015 1:08 pm

I even could not imagine such quick and extremely useful replies to my concerns from qualified experts in this field. I regret I've lost years without knowing this excellent possibility to seek for expert advice and relief. I have spent days and night in worrying and searching for available assessment of our case.

My wife, who is a very good gynecologist, advised me to use the forums to get more in­forma­tion. She cannot do it since she tries to avoid facing unacceptable information that hurts her.

I'm so thankful to you all.

I've thoroughly read your extensive and insightful recommendations, Dr. Shain. You provided precisely the information I was searching for regarding how to treat central nervous system. I have referred to our local doctors to learn the way you described. Thank you for that.

Indeed we are on our way to use irradiation to these two plasmacytomas on spinal nerves. In fact, we do not know when they first appeared, but eye plasmacytoma appeared in summer 2014, then we tried VCD for a second time. But it didn’t work for that, and Avastin helped us. I assume these two spots in spinal nerves date back to that time too.

My question precisely is the following: My wife controls her blood routinely once in a month. Last blood tests were very good, as with normal healthy woman. Is it necessary to conduct systemic treatment in addition to irradiation now if disease is under control in blood? If we do not use systemic treatments, what are the risks?

The treatment options that were described included (1) irradiation, (2) VCD, and (3) VTD-PACE. Should these be done simultaneously, or only 1 and 2, or 1 and 3?

The problem is that my wife had systemic chemo already (VCD), and she felt very bad during the treatment. Now she feels fine and I think she has a good health (aside from her myeloma).

So general question is when is it appropriate to merge localized treatment with systemic treatment?

Many thanks again from my family.

[Katrina]

Re: Extramedullary plasmacytomas in eyes, spinal nerves

by Katrina on Wed Apr 01, 2015 5:18 pm

Hi there!

Somebody told me about your post. We live in Austria, that is near to Germany.

At the moment we are very depressed too because my father had his first relapse in September 2014 too.

The doc recommended Revlimid and my father decided to try 15 mg of Revlimid every day.

Last month he suddenly had problems with his eye and his hands. At first, I fought it was a stroke, or the hyperviscosity syndrome, but the doctor told us that he just has an abducens paresis.

From this point he was in a very bad situation and he couldn't even walk because there are so much pains in his hips too.

The docs also did a cross stitch and they analyzed his cerebrospinal fluid. They didn´t found anything.

I think there is something going on know. At the moment he does a radiation therapy for his pains and for the eye.

The doc told us that there is no extramedullary myeloma.

Thank your for your experience,

Greetings,
Katrin

[Dr. Ken Shain]

Re: Extramedullary plasmacytomas in eyes, spinal nerves

by Dr. Ken Shain on Wed Apr 01, 2015 11:51 pm

A few comments.

1. Therapeutic managment needs to personalized based on past therapy, disease state, your wife's overall health (ability to tolerate therapy) and patient (caregiver) choices / goals.
    
2. Initiation of specific therapy is very personal and I cannot tell you what to do, only what I would like to do depending on the circumstances, and the unfortunate reality is that armchair quarterbacking (an American term for making decisions from a far and without all the facts) is not easy to do.
    
3. If the cauda equina lesions were present in the summer or 2014 and she did not have systemic therapy, she would not be walking today. These are new lesions and need to be taken care of quickly.
    
4. Radiation (localized therapy) and systemic therapy need to be initiated if not simultaneously, then in tight sequence once after the other.
    
5. With the history of VCD failure, Revlimid / dex can be started simultaneously with irradiation. One also could consider the addition of Cytoxan to Revlimid / dex, but I would wait to add Cytoxan until after the radiation is completed.
    
6. VRD [Velcade, Revlimid, dexamethasone] is another triplet that would be a very reasonable and well-tolerated choice to be started with irradiation, unless peripheral neuropathy was noted with previous Velcade.
    
7. If available, pomalidomide [Pomalyst,, Imnovid] / cyclophosphamide / dex, carfilzomib [Kyprolis] / cyclophosphamide / dex, or carfilzomib / pomalidomide / dex would be my non-infusional (outpatient) drugs of choice in this setting.
    
8. The most aggressive therapy – with infusional therapy DCEP, or VTD-PACE – are therapies that would be used to debulk the extramedullary plasmacytomas and other disease and should occur after radiotherapy to avoid radiosensitization (unneeded radiotoxicities).
    
   Subsequently, these therapies would need to followed with something else – possibly with maintenance Revlimid +/- Velcade, or if possible consider an allogeneic stem cell transplant (donor transplant in the setting of early transplant failure and the fact that your wife is 35 years old). This course is heroic – meaning a lot of potential toxicities, mortality, and time in the hospital getting therapy without a guarantee of improved outcome – but address the goal of improved outcome. In my opinion, with a patient who is 35, one has to consider all options and how you feel about treatment.

We all wish you, your wife and your young family the best of luck. Take care.

[Giorgi Galas]

Re: Extramedullary plasmacytomas in eyes, spinal nerves

by Giorgi Galas on Thu Apr 02, 2015 8:05 am

Dear Dr. Shain,

Thank you for your empathy and recommendations, I much appreciate your kind assistance. It is always hard to accept the bad truth.

We are extremely limited in medicines like Revlimid, it is so expensive, no insurance coverage, no public health program coverage.

The only option is Velcade; it worked very well for blood (as proteasome inhibitor), but weak reaction to eye plasmacytomas, since we witnessed the regrow of lesions again four months after we finished VCD and Avastin.

We have to make tough decisions. I will come back with new developments.

Once again, thank you for all your thoughts and advice.

Good luck in your noble efforts.

[TerryH]

Re: Extramedullary plasmacytomas in eyes, spinal nerves

by TerryH on Thu Apr 02, 2015 11:30 am

Hello Giorgi,

I'm very sorry to hear about the situation with your wife. I hope the advice that Dr. Shain and others have provided you proves useful.

If Revlimid is not an option for your wife, you may want to consider substituting thalidomide for Revlimid in some of the options that Dr. Shain listed. Thalidomide, Revlimid, and Pomalyst are from the same family of drugs. Revlimid and Pomalyst are newer drugs, but they are similar and are often combined in the same way with other drugs. For example, the combination of Velcade, Revlimid, and dexamethasone (VRD) is a newer version of the older VTD com­bi­nation.

Thalidomide is more likely to cause problems with peripheral neuropathy, however, than Rev­limid, which is something to keep in mind.

When your wife was treated with Velcade, was she given it as an infusion, or as a sub­cu­taneous (under the skin) injection with a syringe? I have read that, for extramedullary tumors, it may be better to use infused Velcade, rather than subcutaneous Velcade. (Sorry, I can't remember where I read that; I wish I had a reference for you.)

Is taking part in a clinical trial an option for your wife? You can search for clinical trials any­where in the world at clinicaltrials.gov. You can use the "Advanced Search" function to specify "myeloma" as the "Condition", and then scroll down and choose your country, or a nearby coun­try. Here, for example, is a list of open myeloma trials in Turkey:

https://clinicaltrials.gov/ct2/results?recr=Open&cond=myeloma&cntry1=ME%3ATR

(There was only one trial planned for Georgia, and your wife probably wouldn't be eligible for it because it is for newly diagnosed myeloma.)

Good luck!

[Giorgi Galas]

Re: Extramedullary plasmacytomas in eyes, spinal nerves

by Giorgi Galas on Thu Apr 02, 2015 1:39 pm

Dear TerryH,

I'm so grateful for your informative response. I've learned so much from you all and am thankful for this forum and its authors.

Revlimid and Pomalyst are unavailable in Georgia because no one buys it and there is no in­sur­ance or government program that may cover it. The only way is to import from other coun­tries (Turkey, Russia), but it is so expensive / unaffordable.

Thalidomide may seem to be more reachable from Moscow, as I have learned.

The trials are so interesting. I have always been interested in the way how one can get in trials, even experimental ones. We are ready for that, of course, as it makes treatment accessible for us. Thank you for that valuable information. I will do my best to reach that opportunity.

Indeed, we did subcutaneous Velcade, as we were told it causes less side effects. Very useful ad­vice you have provided.

Once again, thank you for your kind assistance. My family much appreciates it.