[DanaH]

Return to MGUS/SMM state after treatment?

by DanaH on Mon Jun 17, 2013 9:21 am

Good morning everyone,

Another member posted the following in response to a question re PCL (Mark, I hope you don't mind that I copied this part of your response, but I wanted to further understand what this means).

" One of the best subgroups of myeloma patients are those that never get a complete response but return to a MGUS/smoldering myeloma state."

Can anyone provide further information regarding this? Are there any articles/research links you could provide?

I found something, but doubt this is what was referenced. http://www.ncbi.nlm.nih.gov/pubmed/23743858

Any help would be greatly appreciated.

Best to all,
Dana H

[Mark]

Re: Return to MGUS/SMM state after treatment?

by Mark on Mon Jun 17, 2013 10:20 am

Hi Dana H.,

I believe that UAMS was the first to write about this in 2007 though I am not sure of that. After they started using Gene Expression Profiling they noticed this.

"Some long-term multiple myeloma survivors never achieved CR, as reported by Fassas et al. (9) among patients treated at the University of Arkansas. Recent gene expression profiling GEP studies revealed that, in comparison with subjects with monoclonal gammopathy of undetermined significance (MGUS), patients with multiple myeloma and a MGUS-like signature enjoyed superior OS despite a significantly lower CR rate, compared with patients presenting with non-MGUS-like multiple myeloma (10). Similarly, in cases of multiple myeloma evolution from a documented MGUS or smoldering multiple myeloma phase, CR was significantly lower without affecting survival adversely (11). These findings indicate that the association between CR and survival does not apply to all patients with multiple myeloma."

"We conclude that (a) CR per se does not confer favorable outcome except in the small subgroup of 13% of patients with truly high-risk multiple myeloma that can thus far only be defined by GEP; (b) lack of CR is not detrimental in the majority of more than 80% of patients with good-risk multiple myeloma; and (c) CR needs to be validated as a surrogate end point for OS in new agent trials in the context of multiple myeloma genetic subtypes as presented here. "

http://clincancerres.aacrjournals.org/content/13/23/7073.full

There are likely more recent examples like the one you pointed out as well. I am sure more recent reports on Total Therapy 3 discuss this as well. This is a discussion of Total Therapy 2.

Mark

[DanaH]

Re: Return to MGUS/SMM state after treatment?

by DanaH on Mon Jun 17, 2013 10:40 am

Hi Mark,

Thanks so much ! this is exactly what I was trying understand further.

All the best to you,
Dana

[Dan D]

Re: Return to MGUS/SMM state after treatment?

by Dan D on Mon Jun 17, 2013 3:56 pm

This is really quite an important point - but it makes me wonder:

These data suggest that striving for an SCR or for MRD by aggressive or extended treatment should not be the end-game for all multiple myeloma patients, especially good risk patients with an MGUS-like signature.

But would such over-treatment be detrimental? Maybe - if it accelerates selection for more aggressive clones. But maybe not - if it slowly but surely wipes out most the clones.

Then again, because people with MGUS can live for decades - indeed some may never progress to active multiple myeloma - reverting to an MGUS state may not only be the proper goal for a subset of patients. It may also be the best way for the patient to hold the body in reserve for treatment by additional agents, especially new ones on the near horizon that may truly convert this disease into a chronic condition - if not offer a cure.