[dishevelled]

Clinical trials for high risk smoldering myeloma?

by dishevelled on Mon May 27, 2013 6:18 pm

I am considered high risk smoldering and I am wondering about your opinions as to whether you think its beneficial to participate in clinical trials or just to use watchful waiting.

My cytogenics put me at high risk. My plasma cells are only at 10-15% witb a large cluster found of 38% and light chain ratio is 16( range .26-1.65)

[terryl1]

Re: Clinical trials for high risk smoldering myeloma?

by terryl1 on Mon May 27, 2013 7:46 pm

Hi Heather, you may have "high risk" SMM due to your cytogenetics, but you may not be "high risk for progression" to active myeloma. They are two separate concepts. Generally, to be high risk for progression, there are various negative factors: skewed K/L ratio; 60% or greater plasma cell infiltration; 95% or greater abnormal plasma cells by flow cytometry; immune paresis, etc. You seem to have a skewed K/L ratio but not in the stratosphere. Your PC infiltration is well under the 60% mark. How about the other factors? Also, Dr. Landgren, an expert on myeloma and its precursors, was interviewed by the MB about all of this fairly recently. You can search for that under the news section. Good luck.

[dishevelled]

Re: Clinical trials for high risk smoldering myeloma?

by dishevelled on Tue May 28, 2013 1:44 pm

I had just read an article where they watched smm patients with t(4;14) and other cytogenic abnormalities and some without. It showed the patients with cytogenic abnormalities progressed to multiple myeloma much faster. I will have to look for it again.

[JimNY]

Re: Clinical trials for high risk smoldering myeloma?

by JimNY on Tue May 28, 2013 2:42 pm

Heather,

This is the article you were probably referring to:

https://myelomabeacon.org/news/2013/03/29/chromosomal-abnormalities-smoldering-myeloma-high-risk-progression/

You also may find this thread useful,

https://myelomabeacon.org/forum/high-risk-smm-mgbs-or-mgus-t1683.html

as well as some of the links and other threads mentioned in that discussion.

Best of luck to you.

[Dr. Ken Shain]

Re: Clinical trials for high risk smoldering myeloma?

by Dr. Ken Shain on Sat Jun 01, 2013 10:00 am

As you all may know the standard of care for a smoldering myeloma patient is "expectant management." To monitor with CBC, CMP, SPEP-IFE, UPEP-IFE, qIgs, and SFLC every 3 moths and imaging annually. This is because as a population patients with SMM progress at a rate of 10% per year. This rate then decreases after 3-5 years to 3% and then almost paralleling that of MGUS (1% per year).

As you can imagine this is not the case for all smoldering myeloma (SMM) patients. To this end, we have tried to figure out who is at the highest risk of progression. Generally, I use the criteria proposed by the Mayo group, dividing patients into three risk groups. The highest risk group of SMM patients will almost inevitably progress to active multiple myeloma within the first 2–3 years following diagnosis defined by bone marrow PC infiltration greater than 10%, serum monoclonal protein greater than 3 g/dl, and abnormal free light chain (FLC) ratio (k to l ratio less than 0.125 or greater than 8).

Percent abnormal PC, circulating plasma cells, PC burden greater than 60% have all been linked to increased risk as well. More recently, as posted, Dr. Rajukumar and the folks at Mayo have also shown that patients with high risk cytogenetics also tend to progressive from smoldering to active disease at a greater rate. However, this has yet to be incorporated into risk stratification (e.g. not used to define high risk SMM in clinical trials to date -- at least as far as i know).

Back to the question: if you are high risk SMM, I feel that it is always reasonable to take part in a clinical trial. Most clinical trials targeting high risk SMM patients are looking to determine if we can improve either the symptoms (bone fractures...) or disease outcomes (overall survival) in SMM. In theory it would be an ideal time to treat myeloma (before it has caused measurable organ damage). However, we do not yet know that is the case.

Early data from clinical trials with Revlimid and dex suggest that it may be of benefit. But I feel we need to better define the high risk population before treatment becomes a standard. Please make sure that you are comfortable with the trial design however.