[JimNY]

Dynamic MRI, smoldering myeloma, and MGUS

by JimNY on Sat Mar 19, 2016 11:43 am

I hope everyone is having a great weekend.

I came across a new study today about smoldering myeloma and MGUS that I thought was worth sharing. It concerns a type of imaging, "dynamic contrast-enhanced MRI", that I didn't know very much about, so I hope you'll forgive me for including in this post some background information I found as I looked around for more details.

Anyway, the results of the new study suggests that dynamic contrast-enhanced MRI imaging can help predict whether a smoldering myeloma patients is particularly at risk of progressing to symptomatic multiple myeloma.

The imaging method does not seem to predict, however, whether MGUS patients are at risk of progression.

In dynamic contrast-enhanced MRI, a series of MRI images are made before and after a contrast agent is given to the patient. The images make it possible to see, for example, what sort of blood flow there is in and around cancer tumors.

The new study was done by researchers in Germany. It included 148 patients with either MGUS or smoldering myeloma. It also included 33 "controls" -- people without myeloma or MGUS.

The study found that smoldering patients who had unusual levels of an MRI metric known as "amplitude A" had an 80 percent chance of progressing to symptomatic disease within 2 years.

It did not seem to find any relationship, on the other hand, between the MRI results and risk of progression for MGUS patients.

The results of this study are not totally new. As I mention below, similar results were published as an ASH abstract a couple of years ago, and that study built on earlier studies, including one published in 2009 by some of the same authors.

The reference and abstract for the current study are:

J Hillengass et al, "Increased microcirculation detected by dynamic contrast-enhanced magnetic resonance imaging is of prognostic significance in asymptomatic myeloma," British Journal of Haematology, March 2016 (abstract)

Abstract:

This prospective study aimed to investigate the prognostic significance of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) as a non-invasive imaging technique delivering the quantitative parameters amplitude A (reflecting blood volume) and exchange rate constant kep (reflecting vascular permeability) in patients with asymptomatic monoclonal plasma cell diseases. We analysed DCE-MRI parameters in 33 healthy controls and 148 patients with monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM) according to the 2003 IMWG guidelines. All individuals underwent standardized DCE-MRI of the lumbar spine. Regions of interest were drawn manually on T1-weighted images encompassing the bone marrow of each of the 5 lumbar vertebrae sparing the vertebral vessel. Prognostic significance for median of amplitude A (univariate: P < 0·001, hazard ratio (HR) 2·42, multivariate P = 0·02, HR 2·7) and exchange rate constant kep (univariate P = 0·03, HR 1·92, multivariate P = 0·46, HR 1·5) for time to progression of 79 patients with SMM was found. Patients with amplitude A above the optimal cut-off point of 0·89 arbitrary units had a 2-year progression rate into symptomatic disease of 80%. In conclusion, DCE-MRI parameters are of prognostic significance for time to progression in patients with SMM but not in individuals with MGUS.

The abstract of this study has a good description of dynamic contrast-enhanced MRI,

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is the acquisition of serial MRI images before, during, and after the administration of an MR contrast agent. Unlike conventional enhanced MRI, which simply provides a snapshot of enhancement at one point in time, DCE-MRI permits a fuller depiction of the wash-in and wash-out contrast kinetics within tumors, and thus provides insight into the nature of the bulk tissue properties.

There is also a Wikipedia article on the topic.

Finally, the new study seems to build on this study presented at ASH in 2013:

J Hillengass et al, "Prognostic Significance Of Parameters Of Dynamic Contrast-Enhanced MRI Detecting Increased Bone Marrow Microcirculation In Monoclonal Plasma Cell Disorders," ASH 2013 annual meeting abstract 3146

and some of the authors of the study also published a related study back in 2009:

J Hillengass et al, "Dynamic Contrast-Enhanced Magnetic Resonance Imaging Identifies a Subgroup of Patients with Asymptomatic Monoclonal Plasma Cell Disease and Pathologic Microcirculation," Clinical Cancer Research, 2009 (full text of article)

[Multibilly]

Re: Dynamic MRI, smoldering myeloma, and MGUS

by Multibilly on Sat Mar 19, 2016 5:06 pm

Fascinating Jim. Thanks for posting this.

I found a video which shows how easy it is to visually pick up a problem via DCE-MRI in both a multiple myeloma and MGUS patient.

See Figure 1 for the video, which is included in this conference poster presentation:

V. Koutoulidis et al, "Dynamic contrast-enhanced MRI parameters correlate with angiopoietin-1/angiopoietin-2 ratio and high-risk features in patients with multiple myeloma," ECR 2015 annual meeting poster C-1674 (link to poster)

Figure 4 shows how easy it is to graph an anomaly picked up by the DCE-MRI.

Now having shared this, I honestly don't know if I want to have any more data available to me that might suggest that my chances of progressing to symptomatic multiple myeloma have increased

[JimNY]

Re: Dynamic MRI, smoldering myeloma, and MGUS

by JimNY on Mon Mar 21, 2016 10:23 am

Thanks for your comments, Multibilly. I know what you mean about whether or not it's worth knowing more accurately what your odds of progression are. You do want to know...but you don't want to know.

What surprised me when I read up about this sort of research is that it has been going on for a long time. I think I found studies from more than 10 years ago that looked at this type of imaging in myeloma patients.

One drawback of this new study is that it uses the old definitions of smoldering and symptomatic multiple myeloma, rather than the revised definitions published in 2014. Maybe there are some subanalyses in the article that split the smoldering patients into subgroups using the new diagnostic criteria.

[CathyAnn]

Re: Dynamic MRI, smoldering myeloma, and MGUS

by CathyAnn on Wed Mar 23, 2016 7:01 am

If this is confirmed with studies at other institutions, I suspect it will still be awhile before it is generally available. Remember that imaging requires interpretation by a radiologist familiar with the technique and experience in reading this type of image. Even if the images are good quality, not all radiologist interpretations are created equal. The same thing goes for pathology reports (which is why they always want to see your biopsy slides when you get a second opinion). It will be interesting to see where this goes. Thanks for sharing, Jim.