[dianaiad]

Indolent vs aggressive relapse: what's the difference?

by dianaiad on Sun Apr 09, 2017 9:54 pm

OK, my numbers are going in the wrong direction. My normally uncommunicative oncologist called me and told me they were, but he's ordering more tests to see and, in any case, 'watch and wait' is the recommended policy, for now.

Like that was a surprise.

I've known my numbers are going in the wrong direction for several months; slowly, but definitely. Until now, though, they've been solidly in the 'normal' range, just going up (or down, whichever is the 'wrong direction.') Now my light chain ratio is 1.8 and I seem to have switched from IgG to IgA for uneven numbers, but none of 'em come close to the numbers I was seeing when I was first diagnosed.

So the question seems to be: what makes a relapse 'indolent' rather than 'aggressive'? Where is the line drawn? How aggressive should *I* be at this point?

[Paul58]

Re: Indolent vs aggressive relapse: what's the difference?

by Paul58 on Mon Apr 10, 2017 7:32 am

Hi dianaiad,

I was diagnosed in October 2013, and achieved a stringent complete remission by March 2014. Over the past 9 months my lambda and kappa numbers began also to slowly slide 'in the wrong direction.' Like you, for months those numbers were still within the normal range (as defined by the lab we use). Finally, in December 2016, 3 months after the previous labs, the lambda was out of range, and the lambda-kappa ratio had fallen to where it was way out of range. All other tests (immunofixation, 24 hour urine) still showed normal readings.

But given the lambda / kappa numbers, my oncologist decided we should do the same treat­ment regimen as my initial treatment - CyBorD (cyclophosphamide, Velcade, and dexa­metha­sone). At first he said just 6 to 8 weeks, but that has turned into the full 16 weeks, with which I am just about finished. All the numbers are back in normal range again. So this time, my oncologist wants me to do some form of ongoing maintenance therapy (which I didn't do last time) to keep things in check. Her are my numbers to give you an idea:

Reference range: Lambda: 5.7 - 26.3 mg/L, Kappa: 3.3 - 19.4, Ratio: 0.26 - 1.65

At diagnosis in 2013: Lambda: 1880 mg/L, Kappa: 14.1 mg/L, Ratio: 0.01
December 2016: Lambda: 258.6 mg/L, Kappa: 23.5 mg/L, Ratio: 0.09
Last week: Lambda: 20.0 mg/L, Kappa: 15.7 mg/L, Ratio: 0.79

All this just to give you an idea of when my oncologist decided to take action. I'm confident it was the right time, even though treatment has upended my schedule and been an inconvenience!

My oncologist can be vague at times (and even gets details scrambled because he's probably way too busy! So if I feel I'm not getting clear answers or he's rushing through things, I nail him down with specific questions and then I do get answers.

Also, I think we all have to keep in mind that as great as the science is, it's not an 'exact' science as every individual is unique, and opinions may differ as to when to treat a relapse, or something that is moving in that general direction.

For me personally, I didn't want to wait until I was feeling sick again to do treatment, but neither did I want to have treatment again with all those harsh chemicals in my body until it was really necessary. And it never hurts to get a second opinion or to ask your oncologist to consult with another myeloma specialist, which I am going to ask mine to do with regards to maintenance therapy.

Blessings to you,
Paul

[K_Shash]

Re: Indolent vs aggressive relapse: what's the difference?

by K_Shash on Mon Apr 10, 2017 1:23 pm

Hello dianaiad,

It may seem that many oncologists give the same answer when a myeloma patient asks about the kappa, lambda, or kappa-lambda ratio levels: "We'll watch these parameters and 'stay the course."

I am in a similar situation, and I have been on 'Revlimid only' maintenance for about 20 x 4-week cycles. Apparently a relapse' is imminent, and I have been researching the Beacon's archives on the subject.

In my case, a myeloma expert advised us that I should expect a relapse (I have only had the induction therapy for my IgG kappa, standard-risk multiple myeloma) in another year or two, adding dex to the dosing may or may not help, and switching to another drug for maintenance would be the best course of action.

Based on most of the articles I came across on this subject, I think the kappa-lambda ratio of 1.8 (normal range: 0.26 - 1.65) is only marginally high, though you must have been tracking these numbers closely and seen them 'creep up'. I really don't know the significance of the IgA levels, however. It is unfortunate that your oncologist has been uncommunicative and I recall your past frustration with him about his comments and reference to chemo brain.

This forum post by Dr. Libby may help a bit. Here's an excerpt:

My current practice (in patients not on a study) in patients having a "chemical relapse" – meaning their SPEP and/or serum free light chains and/or 24 hour urine for Bence Jones proteins are rising BUT the patient does not have CRAB symptoms – is to observe them and follow the IMWG recommendations mentioned already in this discussion.

I would also treat patients with a chemical relapse if the following things were detected:

#1. The free light chain ratio (involved / uninvolved) is > 100
#2. A repeat bone marrow biopsy showed > 60% plasma cells
#3. A bone marrow MRI showed new focal lesions

Based on what you have told us about your case so far, I would probably continue the Revlimid and dexamethasone and follow you closely. If you have not been restaged in the last 6-12 months, a bone marrow biopsy and bone marrow MRI could be helpful to decide if a switch in treatment is required at this time.

[Ron Harvot]

Re: Indolent vs aggressive relapse: what's the difference?

by Ron Harvot on Mon Apr 10, 2017 3:51 pm

Indolent vs aggressive relapse

The indolent relapse is generally slow and non-symptomatic. Thus it is only discovered by ongoing tests. An aggressive symptomatic relapse on the other hand is generally where the change is rapid and accompanied by one or more CRAB symptoms.

With an aggressive relapse more aggressive treatment is usually prescribed. In such cases getting the multiple myeloma under control is the primary concern. With a indolent relapse, Oncologists generally take a more limited approach trying to balance quality of life with treatment.

Hope this helps.

[lys2012]

Re: Indolent vs aggressive relapse: what's the difference?

by lys2012 on Mon Apr 10, 2017 9:44 pm

My doctor talks about "doubling time" that is, how fast your mspike is progressing. Gives an idea of when you would need treatment. My own indolent relapse took almost two years to get to treatment range. I still have little symptons, just some fatigue and some irregular blood counts.

[Janet1520]

Re: Indolent vs aggressive relapse: what's the difference?

by Janet1520 on Thu Apr 13, 2017 12:41 am

Interesting timing of this post as I have been experiencing a similar "creeping" with my numbers.

I've been on maintenance therapy for my high risk myeloma for quite awhile – no stem cell transplant yet. I had 6 months induction starting May 2014 with Empliciti (elotuzumab) plus Revlimid, Velcade, and dexamethasone (RVD) in a clinical trial, and maintenance therapy since then. Starting in June last year, my kappa light chains, which were creeping up within normal range, had finally crept out of range. Since then, they have kept creeping, albeit in very small increments. Some months they drop, but most months just small creeps.

This month the kappa light chain is 3.10 (up from 2.8). My doctor doesn't seem concerned, as he says the increases are very small. He says that when the difference between kappa and lambda is at 10.0 then we will change treatment (per the trial). He also says a high-risk relapse is not subtle.

[Terri Michigan]

Re: Indolent vs aggressive relapse: what's the difference?

by Terri Michigan on Thu Apr 13, 2017 11:07 am

This is the pretty much the same situation that I am in right now. My local oncologist wants me to start treatment now, and things just recently got a little out of range. November has been 2 years since my stem cell transplant, and I have had no maintenance drugs since the transplant except Zometa.

The reason he feels I need to start right away is because he said my light chains and ratio have never been high in the past (diagnosed 8 years ago) but managed to do a lot of bone damage and pain. Currently I have no new pain. Kinda stinks to know you have to start meds that make you feel bad when you feel fine right now without them.

I am seeing a specialist in Lansing to get a second opinion on when and what cocktail he thinks would be best for my situation. I will post back after that visit, probably next week some time. At least from what I have been told and you all just replied, sounds like it is not aggressive at least.

Good luck and keep us posted on what your treatment is.

[Ron Harvot]

Re: Indolent vs aggressive relapse: what's the difference?

by Ron Harvot on Thu Apr 13, 2017 2:02 pm

I should add that I am experiencing a technical indolent relapse. I did not have a transplant and have been on some form of continuous treatment since I was diagnosed a little over 8 years ago.

I originally was on VRD (weekly Velcade infusions later changed to shots, accompanied by 40 mg of dex on the same day as the Velcade and also 10 mg of Revlimid on 21 days, then off 7) plus originally a monthly infusion of Aredia. That protocol was gradually backed down to a shot of Velcade once every two weeks accompanied by 8 mg of dex. The Revlimid was stopped in 2012, and Aredia was moved to once every 3 months.

That has now changed as my numbers slowly increased over the course of the last 1 1/2 years. So my new protocol that started in February has been accelerated to a Velcade shot for 3 consecutive weeks, then off one week accompanied by 20 mg of dex on those same days. Revlimid has been reintroduced at 5 mg on 21 days and off 7. So in essence, I receive treatment for 3 weeks and then have a one-week holiday. Aredia has not been changed.

I have had this protocol now for nearly 3 months and go back in for testing in a couple of weeks to see if it is working.

Ron

[K_Shash]

Re: Indolent vs aggressive relapse: what's the difference?

by K_Shash on Thu Apr 13, 2017 6:11 pm

Thanks, Dianaiad, for starting this discussion.

I would appreciate if you cold post your latest test results and the specifics of any new treatment. I am sure that many Beacon members are on maintenance and the 'relapse' and "Now what?" is on everyone's mind.

Thanks, Ron, for detailing your experience with the indolent relapse.

What parameters are your routine tests monitoring (mine is the non-secretory type, IgG kappa multiple myeloma, and only the kappa and K/L are checked every 4 weeks, along with the RBC and WBC panels)? Could you give us some idea how your M-Spike or the kappa or lambda progressed, during this indolent relapse, as you wrote.

My oncologist, like most others, hasn't really told me what would be the treatment if and when my kappa starts rising. I am not even sure if it hasn't started rising already. My RVD induction treatment started in December 2014 and my kappa came down to 12-15 mg/L (from 1,170) and the K/L to around 1.0 (from about 135) in August 2015.

My induction treatment was 'tapered down'; first by dropping the weekly Velcade and then dropping the weekly 20 mg dex in November 2015. I was doing fine for the 3 cycles after stopping the weekly Velcade shots and my kappa and K/L were stable. I think I had achieved CR or even may be SCR, but I did not want to ask for any bone marrow biopsy just for that. Anyway, dropping the weekly 20 mg dex caused a Revlimid rash on my old 21 days x 15 mg dosing, within about 11 days and I had to reduce the Revlimid to about 15 mg every alternate day. My oncologist is against even a 8 mg weekly dose of dex. I chose not to undergo any autologous stem cell transplant. The mSMART guidelines and the fact that, though not completely drug free, the alternate day 15 mg Revlimid and a daily 81 mg aspirin have been quite tolerable. My onclogist had advised me that I could always consider the stem cell transplant option later.

I am not sure whether to consider the resulting increase in the kappa as any kind of "relapse". My kappa rose to 30 +/- very quickly and K/L to around 1.5 - 1.7 in a few cycles and was stable in that range for about 6 months. Recently, my kappa rose to 50+/- level partially because I stopped all alcoholic drinks for about 3 months. My K/L seemed to remain around 1.65-1.75.

I have been on the 'Revlimid only' maintenance for just over 1 1/2 years now and most of my concerns are met with 'I would stay the course' reply from my oncologist. Therefore, I wonder whether I am experiencing any indolent relapse and what levels would indicate that a more aggressive treatment is necessary. It seems dianaiad's oncologist is concerned enough to look into a more aggressive treatment even at a K/L ratio of 1.8, just slightly above the 1.65 level, the upper end of the 'normal range. I did not quite understand the IgG switching to IgA concerns, though. Is that when the lambda light chains start rising more rapidly?

I am curious about the 'normal' progression of the disease when one is on the Revlimid maintenance to qualify for a 'relapse' (indolent or more abrupt), particularly for those of us that have not had any transplants. Your current treatment gives me some idea of what to expect when my oncologist would need to change my treatment for the 'relapse'.

[Ron Harvot]

Re: Indolent vs aggressive relapse: what's the difference?

by Ron Harvot on Fri Apr 14, 2017 12:31 pm

When I was originally diagnosed I was Stage 2 standard risk IgG kappa light chain multiple myeloma, I did not have an M-spike and was and continue to be tracked by the serum free light chain (sFLC) assay. The serum immunofixation test showed a faint IgG kappa marker but not a measurable M-spike.

I started showing an M-spike starting in October of 2013 at 0.1 g/dL (1 g/L), and it went up as high as 0.3 g/dL then has stabilized at 0.2 since December of 2015.

I started climbing out of the normal range on the sFLC Assay in January of March of 2015 when the kappa free light chain level went to 23.56. it slowly increased to finally going over 100 in November of 2016. The lambda free light chain level has bounced between normal and below normal. The readings before the change in protocol on January 25 (my last test) were:

Kappa - 116.69
Lambda - 6.25
Kappa-lambda ratio - 18.67.

The M-spike was 0.2. A bone scan revealed no new lesions, and a bone marrow biopsy had plasma cells at less than 10%.

So as you can see, the progression was slow over two years. Typically the oncologists wait until the impacted light chain goes over 100 to change things or begin treatment if a patient is not being treated. Of course, that varies if a person has had lesions develop earlier or has a high risk genetic profile like deletion 17p. I did not have any of that.

Hope this helps. The disease is heterogeneous so you cannot really tell much from a single person's experience. This is not like diabetes or even AIDS which are more predictable.