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What exactly is the definition of relapse?

by Don on Tue Dec 16, 2014 6:05 am

Had to take the dex this morning, which means no sleep for me. I've been reading all the ASH studies, and they keep referring to relapse. I know the word's meaning, but what is the term's meaning? I really want to know if I've relapsed, which I never felt I had.

I was diagnosed early, due to pre-op blood work. I did two cycles of Velcade, Revlimid, and dex, which was good enough to harvest five million stem cells for future use. After four months, numbers were creeping up, so I went on Revlimid and dex, twenty one days on, seven off, which has everything good again.

Since there is no cure for multiple myeloma, and everyone is on a maintenance routine, have I relapsed?

Don

Re: What exactly is the definition of relapse?

by Stan W. on Tue Dec 16, 2014 1:39 pm

It doesn't sound as if you've had the usual course of treatment. I went through 7 cycles. Harvested 10 million stem cells and then did 2 more cycles before going on maintenance. I got to CR somewhere around my 4th cycle. Then sCR. But, now back to CR due to abnormal FLC ratio. I'll take it. Could be worse.

Stan W.
Name: Stan
Who do you know with myeloma?: Myself
When were you/they diagnosed?: SMM-April 2012
Age at diagnosis: 58

Re: What exactly is the definition of relapse?

by TerryH on Tue Dec 16, 2014 4:37 pm

Hi Don,

Most likely, you did not technically relapse after your first treatment. Instead, your doctor saw that your numbers were starting to climb much earlier than expected, so the doctor put you on the Revlimid / dex therapy.

However, you'd have to look at your lab results to see if, technically, you relapsed.

Dr. Libby provided the definition of relapse in this forum posting a while back:

https://myelomabeacon.org/forum/asymptomatic-relapse-post-stem-cell-transplant-t3009.html#p16695

As you'll see, there are a lot of factors that can lead to a relapse "officially" occurring.

Here is what he wrote:

International Myeloma Working Group (IMWG) Definition of Clinical Relapse of Myeloma

Clinical relapse is defined using the definition of clinical relapse in the IMWG criteria. In the IMWG criteria, clinical relapse is defined as requiring one or more of the following direct indicators of increasing disease and/or end-organ dysfunction that are considered related to the underlying plasma cell proliferative disorder:

1. Development of new soft tissue plasmacytomas or bone lesions on skeletal survey, magnetic resonance imaging, or other imaging

2. Definite increase in the size of existing plasmacytomas or bone lesions. A definite increase is defined as a 50% (and at least 1 cm) increase as measured serially by the sum of the products of the cross-diameters of the measurable lesion

3. Hypercalcemia ( >11.5 mg/dL; > 2.875mM/L)

4. Decrease in hemoglobin of more than 2 g/dL (1.25mM) or to less than 10 g/dL

5. Rise in serum creatinine by more than or equal to 2 mg/dL (> 177mM/L)

6. Hyperviscosity

In patients who do not have clinical relapse, a significant paraprotein relapse is defined as doubling of the M-component in 2 consecutive measurements separated by less than or equal to 2 months; or an increase in the absolute levels of serum M protein by more than or equal to 1 g/dL, or urine M-protein by more than or equal to 500 mg/24 hours, or involved FLC level by more than or equal to 20 mg/dL (plus an abnormal FLC ratio) in 2 consecutive measurements separated by less than or equal to 2 months.

This definition of “paraprotein relapse” represents the rate of rise or absolute level of increase in M protein at which the panel considered that myeloma therapy should be restarted in relapsing patients in clinical practice, even if signs and symptoms of new end-organ damage are not yet apparent.

Rajkumar. Blood. 2011;117(18):4691-4695)

*Durie BGM, Harousseau J-L, Miguel JS, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20(9):1467-1473.

TerryH

Re: What exactly is the definition of relapse?

by Cheryl G on Tue Dec 16, 2014 5:25 pm

Nice catch, Terry.

I think what Dr. Libby focused on is mainly clinical relapse -- i.e., relapse as demonstrated by the development of new symptoms of multiple myeloma.

He does hint at the definition of serological relapse -- relapse indicated by changes in blood (or urine) lab readings -- when he writes,

"In patients who do not have clinical relapse, a significant paraprotein relapse is defined as doubling of the M-component in 2 consecutive measurements separated by less than or equal to 2 months; or an increase in the absolute levels of serum M protein by more than or equal to 1 g/dL, or urine M-protein by more than or equal to 500 mg/24 hours, or involved FLC level by more than or equal to 20 mg/dL (plus an abnormal FLC ratio) in 2 consecutive measurements separated by less than or equal to 2 months. "

However, I find this description a bit confusing. When I look at this table,

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2627786/table/T5/

it says that serological disease progression is defined as occurring in myeloma patients when there is an increase of 25 percent in either the serum M-spike (minimum increase of 0.5 g/dL) or urine M-spike (minimum increase of 200 mg/24hrs).

I always thought disease progression is the same as relapse, but now I'm not 100 percent sure.

Anyone know the answer to this conundrum?

Cheryl G

Re: What exactly is the definition of relapse?

by Dr. Jonathan Kaufman on Wed Dec 17, 2014 10:07 am

All,

I agree that these definitions can be confusing. There are differences between progression and relapse and they are somewhat subtle.

A patient is considered to have progression if at any time they meet the definition based on the serologic evaluation or new symptoms of myeloma.

In contrast, relapse is more narrowly defined. In order for a patient to have relapsed disease, the patient has to have an initial response and then relapse from that response.

A patient with progression of disease may have either had a prior response or not.

Don, it's hard to know if you had a "relapse" without the exact numbers. This is the time that we would consider moving forward with transplant. Have your doctors discussed that with you?

Best wishes,

Jlk

Dr. Jonathan Kaufman
Name: Jonathan Kaufman, M.D.
Beacon Medical Advisor

Re: What exactly is the definition of relapse?

by Cheryl G on Wed Dec 17, 2014 3:12 pm

Thanks, Dr. Kaufman.

I'm trying to understand this a bit better, so everyone bear with me. I'll keep things simple and just focus on the M-spike criterion.

Say a multiple myeloma patient has an M-spike of 3 g/dL at diagnosis. She undergoes treatment and her M-spike drops down to 0.2 g/dL.

Her M-spike stays there for 2 years and then it goes up to 0.4 one month and the next month it is 0.5.

So her M-spike has been up more than double for two straight readings. Based on the IMWG criteria cited by Dr. Libby, that would qualify as a "significant paraprotein relapse."

However, it wouldn't qualify as disease progression based on the other IMWG criteria I mentioned in my earlier posting, because the patient's M-spike did not go up by at least 0.5 g/dL.

So would this be a relapse?

To put the question another way, if a patient has responded to treatment and then experiences disease progression according to IMWG criteria, is that also automatically a relapse according to IMWG definitions?

Cheryl G

Re: What exactly is the definition of relapse?

by Don on Thu Dec 18, 2014 8:57 am

Dr. Kaufman,

Thanks for responding. I actually see my oncologist today, but he hopes I'll never need the transplant. My Revlimid has been reduced to 5 mg tablets, and he's been happy with the response, but I'll have a lot of questions for him today.

I'm in no hurry for the transplant because that seems like that would be progression. The disease is getting ahead of me in my thinking anyway.

Good news is I'm feeling the best that I've felt in the last year and a half. Side effects are tolerable, my energy is returning, and the foot pain is manageable.

Happy holidays and good health!

Don

Re: What exactly is the definition of relapse?

by Dr. Jason Valent on Mon Dec 22, 2014 7:48 pm

To Cheryl's question: "progressive disese" does officially require an M-protein rising above 0.5 for the scenario that you provide. Most of the progressive disease criteria use measurements of serum or urine M-protein or serum free light chains if no M-protein is present to determine "progression." There are other criteria under "progressive disease" that are also used in the "relapse" category.

In the absence of "progressive disease" criteria, the term "clinical relapse" is used if there are new bone lesions or plasma­cytomas, definite increase in size of bone lesions or plasma­cytomas (50% increase in size and increase by at least 1 cm), hypercalcemia, drop in hemoglobin > 2 grams/dL (without other cause), and increase in serum creatinine by 2 mg/dL or more.

Dr. Jason Valent
Name: Jason Valent, M.D.
Beacon Medical Advisor

Re: What exactly is the definition of relapse?

by Joseph on Tue Dec 23, 2014 11:04 am

Could someone explain to me why having serum creatinine rise by 2 mg/dL is a criteria for relapse? I understand that it is a sign of kidney problems, but could it not be related to other factors and not myeloma? Is there a correlation between serum creatinine level itself and myeloma, or is this criteria taken in conjunction with other factors and used to claim relapse?

Joseph

Re: What exactly is the definition of relapse?

by reach449 on Thu Apr 04, 2019 12:53 pm

I had my stem cell transplant in May of 2017 and my M-spike had always been zero until January this year. In January my M-orotein climbed to 0.24 in January and to 0.21 in February. My lambda free light chain climbed from 2.25 to 3.71. My M-protein was 60 before my transplant.

In December my doctor did change my maintenance drug from 10 mg Revlimid to Ninlaro 4 mg once a week.

So my main question is: Is a climb in labs such as mine automatically considered a relapse even if it was just the new medications that allowed the climb?

Thanks,
Randy

reach449
Name: Randy
Who do you know with myeloma?: self
When were you/they diagnosed?: December 2017
Age at diagnosis: 57

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