Beta 2 Microglobulin

[ColSte]

Hi. I'm considering getting a Beta 2 Microglobulin blood test done. I have CLL and on W&W. Has anyone else had this done?

[cajunjeff]

Hello Colste. My doctor has Beta2microglobulin testing done routinely for me on each visit. Like a lot of bloodwork we do and markers we have, it’s just one marker that yields the best information when viewed over time to look for trends and when read in conjunction with other test result trends.

Here is a med line article that gives more info on beta 2 and its relevance:

medlineplus.gov/lab-tests/b...

[ColSte in reply to cajunjeff]

Thankyou for this. Does it help look at the progression of CLL or just to aim towards treatment options.

[cajunjeff in reply to ColSte]

Colste, I think in a general sense, beta2 is tested in cll patients for the specific purpose of looking at the progression of cll. Not every bump up in micro 2 is caused by cll, but usually beta 2 goes up when our cll progresses.

I have not heard of beta 2 levels informing treatments decisions as IGHV mutation status and fish status can. IGHV testing and fish testing were probably more impt markers insofar as informing treatment decisions in the days of chemo (like fcr) treatment. These markers have less importance with the novel drugs, but cll treatment can be very patient specific. I think for the very best cll specialists, they have the ability to look at multiple factors to guide their decisions which means more info > less info.

[lexie]

My CLL specialist included B2M with the battery of tests for my initial appt in 2015. I remain on W&W and have not had this test repeated since that time. I assume it may have been for a baseline for when treatment comes around.

[AussieNeil Partner Administrator]

I've had 17 tests done; 3 during my 11 years of watch and wait, 2 during treatment and a the remaining 12 done after treatment.

B2M (Beta-2 microglobulin) was developed by MD Anderson as a prognostic indicator for life expectancy with CLL. There was a good correlation with the older chemoimmunotherapy treatments (BR, FCR, etc.) and it has been adopted as part of the International Prognostic INDEX for CLL (CLL-IPI). healthunlocked.com/cllsuppo...

We need an update for targeted therapies. In this paper from 2022;

Prognostic markers in patients with chronic lymphocytic leukaemia on targeted therapy, chemoimmunotherapy with anti-CD20 monoclonal antibody: a systematic review and meta-analysis of prognostic factors

bmccancer.biomedcentral.com...

the note on B2M in the discussion section states, with my emphasis;

The cut-off levels of B2M associated with poor prognosis remain unclear and in untreated CLL patients a value of 2 mg/L [54] while in our analysis B2M levels ≥ 3.5 mg/L [17, 43] were associated with disease progression in treated patients with CLL. Notably in the current analysis, we report on the retained predictive value of B2M in CLL patients on rituximab-containing CIT and maintenance therapy with rituximab. Future studies comprised of diverse patient populations are needed especially in minority ethnic groups to allow for validation of this prognostic marker in the era of CIT and novel targeted therapy. In the era of CIT, and chemotherapy-free CLL management, future studies evaluating the correlations between B2M levels and expression of CD20 and other immune checkpoints in patients with CLL, may assist in the stratification of patients who are most responsive to immunotherapy.

B2M changes over the course of CLL progression. The median survival for B2M<2.1 used to be 12 years in the chemoimmunotherapy era.

Neil

[SeymourB in reply to AussieNeil]

Neil -

> The median survival for B2M<2.1 used to be 12 years in the chemoimmunotherapy era.

Was that <2.1 at first diagnosis, just before treatment, or just after treatment?

=seymour=

[AussieNeil Partner Administrator in reply to SeymourB]

Seymour, I see that you have found some far more recent information on B2M, healthunlocked.com/cllsuppo... but I first learned about it from Chaya Venkat's Workshop III: All About Prognostic Indicators, way back in April 2011 updates.clltopics.net/3256-...

To quote Chaya; "As you can see, B2M level is a pretty good indicator of survival. This graph comes from Dr. Michael Keating’s article in Medscape. The data was collected over a number of years, from 1980 through 2002, I believe. M. D. Anderson uses the cut-off of 2.0 for normal B2M, anything over that is abnormal. The yellow line represents 445 patients whose B2M is normal, under 2.1. Median survival for this bunch was about 13 years. At the other extreme, the white curve is for 175 patients whose B2M was higher than 4.0. Median survival for this group was less than 5 yers.

But once again in pays to remember that general statistics do not guarantee your own track record. Also of note, this data was collected quite a while back, 1980 through 2002. Here we are, almost a decade later than the latest patient in this group. Believe me, a lot has changed – not the least of which is that overall median survival is getting longer in CLL patients! Better drugs, better drug combinations, better understanding of when, who and how to treat patients, better ways of protecting them against infections, second cancers and autoimmune disease – all of this adds up to longer life and better quality of life."

So even back then when FCR was just becoming established as the gold standard CLL treatment, Chaya anticipated better survival times than shown in the attached plots. In fact, the improvements 5 year survival time shown in the SEER data since then, are almost entirely due to "better understanding of when, who and how to treat patients, better ways of protecting them against infections, second cancers and autoimmune disease."

Neil

B2M is a predictor of CLL Tumor Load, but is also influenced by kidney health

[AussieNeil Partner Administrator in reply to AussieNeil]

It takes 5 years to accrue survival data, then some time to process and present the data. That's why the SEER 5 year relative survival plots are currently predicted after 2015 to follow the previous upward trend. Given the median time to treatment after diagnosis is about 5 years, the positive impact of targeted therapy CLL treatments in SEER 5 year survival should begin to appear in the next few years seer.cancer.gov/statfacts/h... We really need 10 year survival time data for CLL - but then we'd need to wait about 12 years to see those results from new therapies!

Neil

US SEER 5 year CLL survival % prediction is only up to 2015 - before common BTKi use

[NoraNoel]

Hi, my doctor did it without me asking for it right at the discovery of CLL. It is supposed to show tumor load. Why do you want to have it done? I am in W&W since November last year.

[ColSte in reply to NoraNoel]

I'm struggling at the moment. Just wanting to know if it is possible to get an idea of the progression of my CLL going forward. Will I need treatment. Just looking for answers that I may never get. 🥲

[SeymourB in reply to ColSte]

ColSte -

I think B2M and LDH rising quicker are rough guides. But no doctor would look at those alone, and say to start treatment. They see those, and then start looking at RBC, Platelets, HgB, lymph node and spleen size, B-symptoms, and lymphocyte doubling time.

The usual indications for treatment are listed in the iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL

ashpublications.org/blood/a...

See the section, Indications for treatment. I don't expect that those indications will change much in the future unless new drugs prove to be significantly less toxic, and provide long progression free survival compared to older drugs. That will likely take several years to prove. In the mean time, some doctors may decide to treat sooner than others, because they know that more treatments after relapse are available.

I would also note that in my case, various values, including B2M, LDH, and ALC rose AND fell, even in the months just before treatment. I get much more testing that the typical person, I think. It just worked out that way.

I just finished treatment on a trial, by the way, and am very happy with the result and care that I got at M.D. Anderson.

=seymour=

[NoraNoel]

So sorry to hear that.. I am new to all of this as well. It is confusing and overwhelming emotionally and physically. It is good that you are here and can get some support. Hope you have a good support around you- family is not usually the best, because they are overwhelmed themselves.

[EugeneL2]

I get B2M tested yearly when I visit my CLL specialist in Houston. It appears 3.5 or less is good. It is a marker for CLL burden but not an indication for starting treatment.

[SeymourB]

ColSte -

In the US, the NCCN (National Comprehensive Cancer Network) Clinical Practice Guidelines do not call Beta-2-microglobulin essential.

"INFORMATIVE FOR PROGNOSTIC AND/OR THERAPY DETERMINATION:[e]

• FISH to detect: +12; del(11q); del(13q); del(17p)

• TP53 sequencing

• CpG-stimulated metaphase karyotype for complex karyotype (CK)

• Molecular analysis to detect: Immunoglobulin heavy chain variable region gene (IGHV) mutation status

• Beta-2-microglobulin"

In regard to prognistics, they cite several papers (references below) for prognostics at various phases of progression and treatment:

"Beta-2 Microglobulin

Beta-2 microglobulin is readily measured by standard laboratory evaluation of blood samples, and an elevated level of serum beta-2 microglobulin was shown to be a strong independent prognostic indicator for treatment-free interval, response to treatment, and OS in patients treated with first-line chemoimmunotherapy. [45,46] However, it is influenced in a CLL disease-independent manner by renal dysfunction."

The first reference [45] is just before treatment on earlier chemo-immunotherapy, the second [46] is after treatment.

On page MS-5, they say:

"More recently, two prognostic models have been developed to predict the outcome of patients treated with targeted therapy. [63,64] The first prognostic model stratified patients treated with ibrutinib into three risk groups (high [3–4 points]; intermediate [2 points]; and low [0 points]) based on TP53 aberrations, prior treatment, beta-2 microglobulin (≥5 mg/L), and LDH greater than 250 U/L. [63] The 3-year PFS rates were 47%, 74%, and 87% for the high-, intermediate-, and low-risk groups, respectively (P < .0001). The corresponding 3-year OS rates were 63%, 83%, and 93%, respectively (P < .0001). This model remained significant in the stratification of patients with treatment-naïve and relapsed/refractory CLL. The second prognostic model allows for the identification of high-risk patients with previously treated CLL who do not achieve a good outcome with available targeted therapies (ibrutinib, idelalisib, and venetoclax). [64] This prognostic model stratifies patients into three risk groups (low [score 0–1]; intermediate [score 2–3]; and high risk [score 4]) using serum beta-2 microglobulin (≥5 mg/dL), elevated LDH, hemoglobin (<110 g/L for women or <120 g/L for men), and time from initiation of last therapy (<24 months)."

The first reference [63] is just before treatment. The second [64] is for relapsed/refractory, not treatment naive.

In my own experience, I had 10 Beta-2-microglobulin tests before treatment. It was 2.1mg/L four years before treatment, and 4.4mg/L the morning just before I started. It had been 3.8mg/L the week before, and 4mg/L 2 months before that. So it can go up and down a bit.

=seymour=

References -

nccn.org/professionals/phys...

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, NCCN Evidence Blocks(TM) Version 1.2024 — December 11, 2023

Download after creating a free patient account.

[45] ncbi.nlm.nih.gov/pmc/articl...

Characteristics Associated With Important Clinical End Points in Patients With Chronic Lymphocytic Leukemia at Initial Treatment

J Clin Oncol. 2009 Apr 1; 27(10): 1637–1643.

Just before treatment prognostic.

[46] ncbi.nlm.nih.gov/pmc/articl...

β2-microglobulin Normalization Within 6 months of Ibrutinib-based Treatment is Associated with Superior PFS in CLL

Cancer. 2016 Feb 15; 122(4): 565–573.

Post treatment prognostic.

[63] ncbi.nlm.nih.gov/pmc/articl...

Prediction of Outcome in Patients With Chronic Lymphocytic Leukemia Treated With Ibrutinib: Development and Validation of a Four-Factor Prognostic Model

J Clin Oncol. 2021 Feb 20; 39(6): 576–585.

"Factors independently associated with inferior PFS and OS were as follows: TP53 aberration, prior treatment, β-2 microglobulin ≥ 5 mg/L, and lactate dehydrogenase > 250 U/L. "

Just before treatment prognostic.

[64] ncbi.nlm.nih.gov/pmc/articl...

Risk Model for Overall Survival in Relapsed or Refractory Chronic Lymphocytic Leukaemia in the Era of Targeted Therapies

Lancet Haematol. 2019 Jul; 6(7): e366–e374.

Just before Relapsed/refractory CLL treatment.