[Ben S.]

GEP Low-Risk and MF Subtype

by Ben S. on Fri Jul 13, 2012 9:28 am

Hi,

My wife just had a GEP (gene expression profiling). She was scored as low-risk but has the MF subtype. Among the CRAB symptoms, she has none except anemia. Her last HGB number is 9.6. So a treatment is on the horizon.

Does anyone else have the similar GEP risk and subtype combination? What treatment approach did you take? What has been the outcome of that treatment?

If any Advisor can jump in and offer advice, my wife and I will be extremely grateful.

Thanks you everyone!

Ben

[JP.]

Re: GEP Low-Risk and MF Subtype

by JP. on Fri Jul 13, 2012 10:20 am

I've heard of GEP, but didn't know myeloma has subtypes. What does MF subtype mean? What are the other subtypes?

[Ben S.]

Re: GEP Low-Risk and MF Subtype

by Ben S. on Sat Jul 14, 2012 12:12 am

JP.:

The MF subtype has MAF or MAFB elevation in gene expressions. It is associated with t(14;16) and t(14;20) but rarely has bone disease. What's strange is my wife's FISH reports never showed any translocations, inclusing t(14;16) and t(14;20). In addition to MF, there are 6 other subtypes, such as HY (hyperdiploid) and LB (low bone disease).

Here is a good review of the subject: http://goo.gl/wgxQH.

Ben

[lucious]

Re: GEP Low-Risk and MF Subtype

by lucious on Sat Jul 14, 2012 12:53 pm

Ben

Where did your wife have the GEP performed?

[Ben S.]

Re: GEP Low-Risk and MF Subtype

by Ben S. on Sat Jul 14, 2012 6:37 pm

lucious:

You can have it performed in any hemotologist's office as part of the bone marrow biopsy. The doctor will need to send the sample to a gene analysis lab, much the same way as you would with a FISH report. However, not all doctors would order the GEP for it has not been used widely as part of the diagnostic tools yet.

Ben

[terryl1]

Re: GEP Low-Risk and MF Subtype

by terryl1 on Sat Jul 14, 2012 8:35 pm

Hi Ben, there is a video on Vimeo with my doctor from the NIH, C. Ola Landgren, the chief of the National Cancer Institute's Myeloma Section, where he touches on these issues. It is an interesting video. He is a brilliant physician and a wonderful guy to boot.

[Ben S.]

Re: GEP Low-Risk and MF Subtype

by Ben S. on Sun Jul 15, 2012 12:10 am

Thanks, Terry. I'll check it out.

[Ben S.]

Re: GEP Low-Risk and MF Subtype

by Ben S. on Sun Jul 15, 2012 1:17 am

Hi, Terry:

I just finished watching the video. Subsequently, using the MEK inhibitor mentioned in the video as a key word, I also found some interesting Blood article. It gives me a good feeling that science is finally catching up with targeted therapy for different molecular classifications of the disease.

The viewing of the video and the reading of the literature also shed light on how we should judge new therapies that are coming through the pipeline. When we read that some drugs are only effective for a small subset of the patients, we tend to be disappointed or even dismissive. But the truth may very well be that those drugs are effective for a majority of the patients that have the same molecular classifiction of myeloma, even though they may be only a small portion of the overall myeloma population. Then that actually is a very big deal!

Thanks again, Terry!

Ben

[Dr. Ken Shain]

Re: GEP Low-Risk and MF Subtype

by Dr. Ken Shain on Sun Jul 15, 2012 9:43 am

Your risk profile was described by an analysis examining the expression of 70 genes using a Affymatrix microarray platform. The expression of genes can be from the known genetic anomalies as well as from unknown disease and patient specific signaling within the myeloma cells. It is currently commercially available via Signal Genetics as MyPRS (myeloma prognositc risk score). This 70 gene array was based on the excellent work by Drs Zhan, Shaunnessy, Barlogie and colleagues at in Arkansas in correlation with their total therapy trials. They identified 6 (some suggest there are more) distinct gene expression profiles within patients with myeloma (MF-MAF, PR-proliferation, LB-low bone disease, MS- MMSET, CD-1 (CCND1/CCND3-1, CD-2- CCND1/CCND3-2), and HY-hyperdiploid). These are measures of expression of specific messenger mRNA. This does not always correlate with the metaphase cytogentics of FISH- both are examing specific genetic anomalies associated with myeloma, but as stated is infuenced by them.

This data led to the identification of high and low risk patient populations that could be identified by a 70 gene profile. I believe that this test represents an interesting push/addition to our risk stratification. An updated 80 gene profile is being examined currently.

How to use it? And what does it mean?

We use MyPRS on a regular basis, however, I continue to utilize metaphase cytogenetics and FISH as the basis to define my treatment desicisons. Continuing to see how MyPRS will inform these decsions remains an important goal. From personal experience The high risk MyPRS remians more significant (ie I treat has high risk). However, I have patients who are defined Low risk by MyPRS, but high risk by metaphase cytogenetics and FISH- these patients are treated as high risk in my clinic.

Therefore, in your case I would consider you Standard Risk, based on your metaphase cytogenetics, FISH, and MyPRS.

[Ben S.]

Re: GEP Low-Risk and MF Subtype

by Ben S. on Mon Jul 16, 2012 11:39 pm

Dr. Shain:

Thank you very much for the analysis. You mentioned metaphase FISH. But my wife's FISH was performed on interphase cells. Does that make a difference? If the subtype MF does not change the overall view of the disease as a standard risk variety, does it affect the treatment protocol at all?

With the choice of treatment option coming up soon, we are torn between choosing a conservative and aggressive approach. An aggressive approach has its significant side effects, but a conservative one risks the disease's becoming resistant, given what the MF subtype implies. What is your normal clinical approach under the circumstance?

Many thanks!

Ben