[K_Shash]

Options for rising kappa free light chain level?

by K_Shash on Wed Apr 25, 2018 7:05 pm

Hello everyone,

I was diagnosed with the IgG kappa light chain multiple myeloma in late 2014. I started my induction therapy in mid December of 2014. At the time my kappa level was almost 1,100 mg/L and kappa-lambda ratio was close to 190. The normal levels are 3.3 - 19.4 mg/L for kappa and 0.26 - 1.65 for the kappa-lambda ratio.

My kappa and kappa-lambda ratio dropped to "normal" levels after about 8 months of Revlimid, Velcade, and dexamethasone (RVD) induction therapy, and my kappa was down to 12.5 mg/L and kappa-lambda ratio near 1.1 in August and September of 2015. Stopping the Velcade didn't seem to make much difference. However, my kappa and kappa-lambda ratio readings started rising immediately after stopping dex. My Revlimid dose had to be decreased since I developed the Revlimid rash in the middle of my 3-week "on"cycle, right after stopping the dex.

Therefore I tried a 3-weeks "on" and 1-week "off" cycle of 10 mg Revlimid and also the alternate day 20 mg and the recent 15 mg of Revlimid. At first my kappa rose to 40 +/- mg/L level and later settled around 50+/- mg/L levels; over the last 2+ years. My kappa-lambda ratio remained in or near the normal range throughout this period, until the last 2 months. It has been 2.06 and 2.15 over the last 2 months compared to the 1.74 and 1.75 readings before that.

My kappa level and kappa-lambda ratio have started rising after almost a year of stable readings of kappa at 50+/- mg/L, kappa around 60 mg/L, and my kappa-lambda ratio rising from around 1.75 to 2.15, though I have been on the 15 mg alternate day Revlimid only maintenance for a year and a half. My main side effect has been reduced stamina level and the Revlimid diarrhea. I have been carrying out most of my business activities, I continue to take regular walks, play some golf in good weather, and manage weekly business trips that involve driving for 2 hours each way.

I compared my overall blood test results over the past 2+ years and it seems that my kappa level and kappa-lambda ratio were stable and closer to normal at 40+/- mg/l and the kappa-lambda ratio around 1.6 when I was on a 20 mg alternate day Revlimid. My oncologist agreed to let me go back to that dosing. I just started the higher dose of Revlimid in the middle of this week. I hope to see some drop in my free light chain results over the next couple of months.

I have been researching about some guidelines for the inevitable increase in these readings. Should I repeat my induction therapy if and when the kappa level reaches above 100? The main worry is, of course, any bone decay and fractures caused by the deeper lesions on any bones. I also wonder why many patients try different drugs when their myeloma markers start rising instead of repeating a few cycles of their original induction therapy. The new drugs have unexpected side effects and some involve long hospital visits.

I couldn't find any definitive advice or guidelines about the "non-transplant" patients like me who have rising levels of kappa and kappa-lambda ratio. Therefore, I am trying to extrapolate the advice and guidelines for the diagnosis of active vs. smoldering myeloma, and also for the transplant recipients that may be 'relapsing'. The articles on the 'Relapse after a transplant' mention the rapid rise in the M-spike and also kappa levels rising above 200 mg/L (20 mg/dL) usually accom­pa­nied by high kappa-lambda ratio (much higher than your current levels) as the indicators of "relapse" and recommend starting some therapy.

My main problem with Revlimid for me was that I could not tolerate the 15 mg x 3 weeks on (never reached the one week off) as soon as the dex was stopped. I got a severe Revlimid rash on my legs. My oncologist didn't want me to use the dex at all and reduced my Revlimid dose and essentially said that I could 'live' with the higher kappa! But my kappa level was around 30 mg/L in those days.

So far, my annual x-rays have been stable and my bone density survey seemed to be normal, too. My vitamin D level was low (around 20) last year so I have been taking calcium and vitamin D supplements. I don't think they should affect the effectiveness or absorption of Revlimid. The cholestyramine that I have to take for my severe Revlimid diarrhea did cause some problem and my oncologist advised me to keep those two drug doses apart by about 12 hours. That brought my kappa and kappa-lambda ratio that had abruptly increased by almost 25% back down to the prior levels. I wonder whether my 15 mg alternate day Revlimid was just barely enough to keep my myeloma under control. I will know if the 20 mg level helps.

In my case, is it really worth staying off the dex? Also, what level of kappa would be high enough to make the bone lesions start spreading? And should I just repeat the RVD Induction level cycles if and when my kappa readings exceed 100 mg/L?

[Nancy Shamanna]

Re: Options for rising kappa free light chain level?

by Nancy Shamanna on Thu Apr 26, 2018 9:37 am

Hello K_Shash,

Thanks for sharing the details of your treatments to date and also your concerns with the light chain levels and how to best manage them.

I am not a doctor, but I wonder how you knew that the Velcade was not working for you? And if the Revlimid does cause more rashes, would you consider switching over to another type of drug? The Revlimid, being an oral drug, is very convenient to take, but there are other treatments too if you need them. When I relapsed in 2014, a strong dosage of Revlimid (25 mg, three weeks out of four) plus dex (20 mg/week) worked to lower the monoclonal levels to unrecordable. My doctor thought that the dex was helpful in doing that.

Maybe you could talk to the oncologist and express your concerns about what to do next if the Revlimid causes more negative reactions.

Best wishes!

[K_Shash]

Re: Options for rising kappa free light chain level?

by K_Shash on Thu Apr 26, 2018 1:10 pm

Thanks Nancy.

Just to clarify: Velcade must have worked fine for me during the induction. The combination of Velcade, dexamethasone, and Revlimid brought me to the stringent complete response (sCR) levels (though I did not want my plasma level checked with another bone marrow biopsy). Velcade was stopped only at the end of my induction therapy and to transition to the long term 'Revlimid only' maintenance. And the oral Revlimid is very convenient, indeed.

My myeloma markers, kappa, and the kappa-lambda ratio were stable at the low levels I had achieved after the Induction therapy when I was taking the maximum tolerable Revlimid with the supplemental dex. I wanted to drop the dex down to a weekly 8 mg from the induction therapy dose of 20 mg. However, my oncologist is against the long-term use of even the reduced dose of dex and told me that 'it's long term side effects are not worth the benefit!".

It seems that the hematologists-oncologists are almost equally divided on the use of dex. Some of my oncologist's colleagues apparently do prescribe dex, as I found out accidentally. Similarly, some oncologists consider autologous stem cell transplants as a 'standard of care'. I do plan to bring up the dex supplement again with my oncologist if my kappa level and more importantly the kappa-lambda ratio continue to rise in spite of the higher Revlimid dose.

Just curious: are you on a maintenance dose of Revlimid and/or dex now; after the strong dosage after relapse? If necessary, I'm sure that my oncologist would agree to a dex supplement for a definite period of time and I can go back to 'Revlimid only' maintenance after a substantial reduction in my kappa and kappa-lambda levels.

I appreciate your post and sharing your experience. Thanks to the Beacon, it is possible to share such information and get better understanding of this horrible disease, anywhere in the world.

[Nancy Shamanna]

Re: Options for rising kappa free light chain level?

by Nancy Shamanna on Thu Apr 26, 2018 3:25 pm

Hi K_Shash,

Thanks for your reply. I also appreciate the Beacon and being able to communicate with people in many countries.

To answer your question about maintenance Revlimid, no I am not taking any myeloma drugs currently. I was on the strong dose of Revlimid and dexamethasone when I was diagnosed with a second cancer too. By this time it was September 2016 and I needed surgery and radiation treatments. Since I was doing well with the myeloma at 0.8 g/l (0.08 g/dL) and the kappa-lambda ratio at 0.94, my oncologist decided to pull me off treatment. (My monoclonal proteins seem only to have been below measurable levels after my first year of treatments.) Surprisingly to me and the medical people, I have not needed to resume treatment for the myeloma yet. My kappa and lambda levels and ratio are in the normal range and the M protein is quite low also. If the 'M' protein started to increase quickly, and reach the level of 5 g/l (0.5 g/dL), I think that we would start to think about what to do next. A second relapse is worrisome of course, and probably I will have to deal with that in the future.

I asked you about the Velcade since it is given in subcutaneous injections now which I under­stand is not a really difficult treatment. Also there are other completely different sorts of treatments from proteasome inhibitors and immunomodulatory agents, such as monoclonal antibodies (e.g., Darzalex), for treatments too.

Probably lots of us patients worry about the same sorts of problems as to how to best manage the myeloma!