[Cheryl G]

Re: Meaning of high kappa light chains?

by Cheryl G on Fri Feb 20, 2015 5:49 pm

I agree, Multibilly, that at this point it's probably best to wait until the March blood tests to see if the kappa light chain result was a fluke.

I guess the open question is whether the kappa level in Christina's January's test results was high enough to warrant a quick re-test, or at least a follow-up test within a month. I would have thought so, but I'm also not a doctor.

I also would think that, if the March test results come back confirming the January results, that it would be cause to re-think Christina's treatment regimen. Does anyone know if there is some generally accepted kappa or lambda light chain level that, if exceeded (and confirmed), sug­gests the need for revised therapy, or staring therapy again? Or is it more the kappa-lambda ratio that matters?

Not to mix things up too much, but if Christina's January results are confirmed, would this be a case of "light chain escape"? Or does that description apply only when no M-spike is present at all?

Good discussion. Sorry, Christina, if it things are getting a bit technical, and they're not as con­nected to your immediate concerns as you might prefer. It just takes some thinking through, but we'll get there!

[Multibilly]

Re: Meaning of high kappa light chains?

by Multibilly on Fri Feb 20, 2015 10:31 pm

Hi Christina,

Cheryl makes a really good point about the potential issue of "FLC escape".

FLC escape can occur when a subclonal line of plasma cells begin producing an excess amount of a given free light chain relative to the expected amount of monoclonal heavy chains that it would also normally produce (monoclonal heavy chains are the things measured by your M-spike).

As I understand it from my readings, one's M-Spike doesn't have to be completely absent in order for there to be a diagnosis of FLC escape. But, as always, I'm not a doc, so please check with one.

Note that FLC escape can "potentially" signal a situation where a subclonal line of plasma cells has developed that may be resistant to the current treatment and/or signal a relapse. It's not a given that this is what is occurring in your case, but both Cheryl and I are thinking that the rise in your FLC level ought to be discussed further with your doc.

You may want to read through this article:

A Brioli et al, "Serum free immunoglobulin light chain evaluation as a marker of impact from intraclonal heterogeneity on myeloma outcome," Blood, May 2014 (full text)

It contains a couple of statements potentially relevant to your case:

In 46 of 54 patients (85%), the increase in involved serum FLC was >200 mg/L, that is the level of increase recommended for defining relapse requiring treatment in the absence of clinical symptoms"

Also:

Monitoring for light chain escape at relapse provides an excellent tool to study the global impact of intra-clonal heterogeneity. Our observations fit with a model in which different clones have a different secretory behaviour. One clone is able to produce a complete antibody, while the other secretes only FLC. In such a model FLC escape is a marker of a heterogeneous disease and represents the outgrowth of the clone producing only light chains, which is more resistant to therapy. The results presented here provide evidence to support the idea that intra-clonal heterogeneity and clonal evolution is a general feature associated with disease progression and treatment resistance in myeloma. These results also illustrate the importance of disease monitoring using FLC analysis when there is a suspicion of clinical relapse".

Again, we aren't docs by any stretch of the imagination, and we aren't trying to worry you, but it may be wise to get re-tested and to discuss this a bit further with your specialist.

Take care and let us know what happens.

Last edited by Multibilly on Sat Feb 21, 2015 8:22 am, edited 1 time in total.

[Cheryl G]

Re: Meaning of high kappa light chains?

by Cheryl G on Fri Feb 20, 2015 11:05 pm

Hello Christina,

Just to follow up briefly on what Multibilly wrote, the main thing he and I feel is that it is im­por­tant that you get your blood tests done again in March (hopefully early March), as you had planned, and then discuss the results with your doctor.

If the results in March are similar to what they were in January, then it also is important for you and your doctor to discuss the fact that you seem to be experiencing "free light chain escape", and this probably means your treatment should be changed to get your disease under control again.

Can you remind us again whether the oncologist you regularly see is a myeloma specialist? If they are not, they may not be familiar with the possibility of free light chain escape occurring, which makes it all the more important that you proactively raise the issue with them.

I think I can speak for all of us here when I say that we hope the January light chain results were just a fluke, and that your next set of results makes all of the discussion we've had here unnecessary.

Let us know if we can be of any more help.

Good luck!

[Christina]

Re: Meaning of high kappa light chains?

by Christina on Sat Feb 21, 2015 12:13 pm

Thank you both so much.

My doctor is not a myeloma specialist, but a hematologist / oncologist. He has treated me, though, for my entire time, and is always spot on with treatment and concerns.

I e-messaged him after posting this and he said my last blood test in February before I saw him showed about the same with the kappa light chains. I haven't gotten the report yet to see that specific number. So this is not just a fluke in the testing.

So he responded quite promptly with, the plasma cells are now producing light chains, another antibody. He said it would be of concern except there is no other evidence of myeloma activity (based on all the tests) He said, for now, all he can say is that I'm producing the light chains. So, since nothing is raising a flag and after the other tests, I feel somewhat clearer about it.

I will get tested in March again. I will bring up with him the FLC escape as a topic.

Since I've been on Revlimid so long, it may be I'm becoming refractory to it and will need to switch it up. He is always very open to discussion and has never steered me wrong. I guess I trust his expertise.

On the other hand, I would like to seek out a specialist this year, but haven't quite decided where. Anywhere would mean travel for us. In LA is Dr Berenson. That would be a flight or drive. We are 3 hours from San Francisco, or I've considered the Seattle Cancer Center, also a flight.

So, I guess I'll wait and see what comes up in our March appointment.

It certainly is a little disconcerting but I see him in 3 weeks, so till then.

Multibilly - I just re-read your last post, and I'm thinking that you may be right and I've become refractory to Revlimid. I will bring up other treatment options. I've not done Velcade yet, and that would mean a once-a-week trip in to get that. I live about an hour away, so not too convenient, but doable. I don't think I'd try pomalidomide (Pomalyst / Imnovid) just yet, but we'll see what he says.

[TerryH]

Re: Meaning of high kappa light chains?

by TerryH on Sat Feb 21, 2015 12:33 pm

Hi Christina,

If you're in northern California, UCSF has a number of myeloma specialists, and there are a couple at Stanford also, I believe.

I've heard that there may be a myeloma specialist or two at UC Davis, but I just checked their website, and I get the sense that most of the hematologist-oncologists there are either general hematologist-oncologists, or focused on something other than myeloma. But I can't say for certain.

If you're somewhere between LA and San Francisco, then Dr. Berenson obviously would be someone to consider, as well. City of Hope also has a number of myeloma specialists.

Best of luck to you.

[Multibilly]

Re: Meaning of high kappa light chains?

by Multibilly on Sat Feb 21, 2015 12:41 pm

Hi Christina,

Terry pretty much took the words out of my mouth. If you let us know approximately where you live, folks might be able to give you some more specific suggestions. Since you mentioned Seattle, the Seattle Cancer Care Alliance would be the place to seek out there.

[TerryH]

Re: Meaning of high kappa light chains?

by TerryH on Sat Feb 21, 2015 12:57 pm

Completely agree about Seattle Cancer Care Alliance. Dr. Libby, who has been posting for a long time here in the forum, is there.

There is also at least one myeloma specialist, Dr. Emma Scott, at Oregon Health & Science University in Portland.

[Christina]

Re: Meaning of high kappa light chains?

by Christina on Sat Feb 21, 2015 3:53 pm

I'm about 50 minutes from Sacramento off of I-80 on the way to Tahoe. San Francisco would be the closest drive. But I'd consider other places too.

That's one reason I've never gone that route. It all seems like too much to do! But I will consider it this year.

[Stann]

Re: Meaning of high kappa light chains?

by Stann on Sat Feb 21, 2015 5:42 pm

Hi Christina,

I live about 3 hours from SF and I am very happy with the specialist I see there, Dr Wolf. I have a friend who sees the other multiple myeloma specialist (Martin), and we're both very happy with our treatment.

My doc does a great job of presenting me with options and opinions based on many years of experience. And he gives me a lot of leeway in how I'm treated too, which I like.

We visited with Stanford and UC Davis and decided UCSF was best for us.

I'm pretty sure those two docs at UCSF treat the most multiple myeloma patients in northern California.

[Dr. Ken Shain]

Re: Meaning of high kappa light chains?

by Dr. Ken Shain on Sun Feb 22, 2015 9:59 am

I'm assuming that you have IgG kappa multiple myeloma.

Unfortunately, it appears that you are having light chain escape, meaning that a clone of your myeloma cells (i.e., a subset of the cells) has developed that is only able to make the light chains, is no longer sensitive to the Revlimid / dex and is growing in your bone marrow. Even with the "stable" 0.3 g/dL M-spike, you are progressing (we have to look at the worst).

Fortunately, you do not have any signs of end organ damage (CRAB symptoms) yet. At this time, monthly labs are in order to assess the rate of increase. As such, you are not in a race to start new therapy.

However, I would recommend that you begin to be prepared for the next line of therapy. A kappa light chain of >700 above normal, all of a sudden, would suggest that you are rapidly progressing and could start new therapy at any time (on or off a clinical trial). If it has been slowly climbing, then continued observation can be a management strategy. It really depends on the context.

As others have posted, I would recommend that you

1. See how this number relates to kappa light values over the past several months,
2. Raise your concerns to your heme / onc (he/she may already have gone through all of this in his/her head)
3. Consider seeking a myeloma expert's opinion; you have already been given a number of excellent folks on the west coast.