Hello, myeloma world. We hope your week has started well.

We have one main item on the agenda for today's edition of Myeloma Morning.

In particular, we want to discuss a topic that is the focus of the only article in our daily list of new myeloma-related research publications, included at the end of this report.

The topic of that article is monoclonal gammopathy of renal significance (MGRS).

Now, most Beacon readers probably have heard of monoclonal gam­mop­athy of undetermined significance (MGUS), an early stage of multiple myeloma that remains benign in most people diagnosed with it.

But few Beacon readers are likely to know what MGRS is.

So we thought we should spend some time explaining how MGUS and MGRS are similar and how they are different.

Given the focus of the rest of today's report, we think it only fair to say right now that it mainly will be of interest to two groups of readers.

One group will be people with MGUS who may want to make sure their diagnosis is correct.

The other group is readers with a general interest in conditions that are related to multiple myeloma.

We also want to mention that, for the first time in a while, this report includes a list of Beacon forum dis­cus­sions that may be of interest to our readers. It is included near the end of the report.

Finally, before we move on to the main part of our report, we want to thank the Beacon's newest sponsor, the John C. Davis Myeloma and Amyloid Program at Tufts Medical Center, for its support of our work.

Sponsors such as Tufts are key to the Beacon's ability to provide reliable, up-to-date news and support to the multiple myeloma community worldwide.

Monoclonal Gammopathy Of Renal Significance

The list of new myeloma-related research that is at the bottom of every edition of Myeloma Morning has only one entry today. It is an article about monoclonal gammopathy of renal significance (MGRS) (full text).

The focus of the article is on the different types of laboratory tests that are involved in determining if someone has MGRS. Many of these tests are ones that also are used in the diagnosis and monitoring of multiple myeloma.

Thus, because the full text of the article is available at no cost, many Beacon readers may find it worth re­view­ing at some point. The dis­cussion about alternatives to the Freelite assay for serum free light chain testing, for example, may have information that is new for many readers.

Right now, however, we'd like to use the publication of the article as a springboard for familiarizing our readers with what MGRS is.

To understand what MGRS is, it is useful to start with a discussion of the related disorder, monoclonal gam­mop­athy of undetermined significance (MGUS).

People with MGUS are similar to people with multiple myeloma, in that they have mutated (clonal) plasma cells that are producing monoclonal proteins. These monoclonal proteins are either causing an M-spike, or high levels of one of the patient's free light chains (kappa or lambda), or both.

In people with multiple myeloma, however, there are so many clonal plasma cells that either the cells are doing damage to the body (typically the bones) or the mono­clonal protein is doing damage to the body (typically the kidneys). This is an important reason why the disease is actively treated.

In people with MGUS, the disease is at such a low level that neither the clonal plasma cells nor the monoclonal protein is doing any damage to the body. So the disease is not treated and, in most people with MGUS, the disease will continue to be benign for the rest of their lives.

The situation is different in people with MGRS. These people have a monoclonal protein, and it is at a low level, just as it is in people with MGUS. However, in MGRS, the low level of monoclonal protein is doing damage to the kidneys. That is the reason for the “renal significance” part of the name – “renal” means “kidney-related”.

Thus, MGRS includes “all monoclonal gammopathies that are associated with the development of a kidney disease but do not meet the definition of symptomatic multiple myeloma or malignant lymphoma.”

MGRS was not defined as a disease until about five years ago, when researchers decided it was time to have a diagnosis for a condition that required treatment, but often wasn't being treated because of the diag­nosis patients were being given. A lengthy paper describing the diagnosis of the disease is available in full online, as is a shorter background paper and a description of how some leading specialists treat the disease.

For some perspective on MGRS, we discussed it with Beacon Medical Advisor Dr. James Hoffman of the Sylvester Cancer Center at the University of Miami. Here are the questions we asked, along with Dr. Hoffman's replies.

Do physicians – particularly myeloma specialists – accept MGRS as an entity, or is it still controversial?

Dr. Hoffman - I think they do. However, there is confusion surrounding it – whether it is truly a unique condition, or a term for yet undiagnosed conditions, such as amyloidosis, light chain or heavy chain depo­si­tion disease, etc.

What would you say are the things that are typically included under the umbrella of MGRS?

Dr. Hoffman - Amyloidosis, monoclonal immunoglobulin depo­si­tion disease (MIDD) (light chain depo­si­tion disease, and heavy chain depo­si­tion disease), early myeloma kidney, and cryo­globuli­nemia.

What is the usual approach to diagnosing a patient with MGRS – to the extent that there is a usual approach?

Dr. Hoffman – It is very individualized. When I have a patient with renal injury and a monoclonal gam­mop­athy, I work them up very completely. If there is a cardiomyopathy or carpal tunnel or bruising, etc., I will get a fat pad biopsy to rule out amyloidosis. If there is hypertension, vasculitic rash,  etc., I will test for cryoglobulins. And if there is any indication that the gam­mop­athy is possibly causing the renal damage (that is, an MGRS), then renal biopsy is the gold standard.

How is MGRS treated?

Dr. Hoffman – If the monoclonal proteins are causing renal injury, then the cells producing them are targeted for treatment. If they are classic plasma cells, then typical anti-myeloma therapy is used. If they are lymphoma-like cells (as is often seen in IgM gammopathies), then lymphoma therapies are often used. The principle is to eradicate the causative clone.

Beacon Forum Activity

There has been a lot of activity in the Beacon forum since the last time we highlighted discussions taking place there. Here are some recent posts and discussions that readers may find interesting:

• Forum members are discussing if long-distance travel is advisable soon after being diagnosed with multiple myeloma (link to discussion).
• CindyBrown, a forum member who had a mini allogeneic (donor) transplant one year ago, has posted an update about her current status (link to post).
• Jo Anne, whose husband is undergoing initial treatment for multiple myeloma, would like to know who decides on stem cell transplant eligibility (link to discussion).
• Forum member MrPotatohead is having persistent bone pain despite being in complete remission. He is wondering what the source of his problems may be (link to discussion).
• Aussie Annie, who has MGUS, was treated for a serious infection with antibiotics known to cause bone marrow suppression. She would like to know how long it will take for her bone marrow to recover, and whether the suppression can cause a temporary change in her free light chain levels and ratios (link to discussion).
• New forum user brandonmom was treated for a plasmacytoma on her back on 2014. The plasmacytoma has recurred in the same place. She has asked if this has happened to others, and whether she needs systemic treatment or if radiation will be sufficient (link to discussion).

New Myeloma-Related Research Articles

1. Leung, N., Barnidge, D. R. & Hutchison, C. A., “Laboratory testing in monoclonal gammopathy of renal significance (MGRS)” in Clinical Chemistry and Laboratory Medicine, April 23, 2016 (full text)