Nonsecretory Multiple Myeloma
Nonsecretory myeloma is a topic shrouded in apprehension and mystery.
Patients with nonsecretory myeloma have a host of questions. How do I track the progress of my disease? Should nonsecretory myeloma be treated differently than “standard” myeloma? Is my prognosis different because I am nonsecretory?
Among myeloma patients with secretory disease, nonsecretory myeloma is something they often have heard of, but they are not always sure what it is, or whether it is really relevant to them.
Given the many questions and concerns related to nonsecretory myeloma, I thought I would devote my first column here at The Myeloma Beacon to the subject.
Some Basics
Less than 5 percent of all patients with multiple myeloma have nonsecretory myeloma. Their disease cannot be diagnosed or tracked by the presence of monoclonal (M) protein in the blood and urine or immunofixation studies; however, it can be detected in the bone marrow or upon biopsy of bone lesions.
In the past decade, since a blood test called the serum free light chain assay became widely available, it has been noted that about 60 percent of patients who were previously considered to have nonsecretory myeloma produce light chains, which means that they are not truly “nonsecretory”. However, most studies include this group of patients when they refer to patients with nonsecretory myeloma, so for the purpose of this discussion, I will include this group as well.
Patients with nonsecretory myeloma can be divided into two categories:
- True Nonsecretory (or “Producer”) Myeloma - Patients who have M-protein detectable in malignant plasma cells by special stains; however, the patients do not secrete M-protein. These patients make up 85 percent of all patients with nonsecretory myeloma
- Nonproducer Myeloma - Patients who do not have any detectable M-protein even within the malignant plasma cells. These patients make up 15 percent of all patients with nonsecretory myeloma.
Diagnosis and Follow-up
The absence of proteins in the blood and urine can sometimes delay the diagnosis of myeloma. So it is important when patients undergo initial workup for bone lesions noted on scans that the possibility of nonsecretory myeloma is considered, even if blood and urine do not show evidence of the disease. Biopsy of bone lesions or the bone marrow will usually lead to a correct diagnosis.
Once a patient has been diagnosed with nonsecretory myeloma, the initial diagnostic evaluations and assessment of response should be tailored specifically for nonsecretory myeloma. Since blood and urine studies are not helpful, we have to rely on bone marrow examination, myeloma survey (X-ray), positron emission tomography (PET), and magnetic resonance imaging (MRI) to evaluate this type of disease.
In patients who have detectable free light chains in the blood, free light chain assays should be used to monitor the disease.
At the University of Arkansas for Medical Sciences (UAMS), we do bone marrow exams, PET, and MRI about once every month or every other month during induction therapy and transplants. The exams are scheduled every three months during the maintenance phase and eventually once a year when the disease has been in remission for more than five years.
Treatment
Patients with nonsecretory multiple myeloma are treated the same way as other patients with multiple myeloma. The first step in the treatment process is to determine if a particular patient is eligible for autologous stem cell transplantation or not.
The decision is based on several factors, including age, activity level of the patient, and condition of heart, lungs, liver, and kidneys. The age threshold for transplants varies across institutions; at our institution, we do transplants in patients of up to 75 years of age.
The initial induction therapy for patients who are eligible for autologous transplantation generally consists of a two- or three-drug combination of the following agents: Velcade (bortezomib), thalidomide (Thalomid), Revlimid (lenalidomide), dexamethasone (Decadron), cyclophosphamide (Cytoxan), and doxorubicin (Adriamycin).
After induction therapy, stem cells are collected using cyclophosphamide and white blood cell growth factors. The autologous stem cell transplant is usually done with melphalan at a dose of 200mg/m2.
In the past, the practice was to observe patients after the transplant without the use of maintenance therapy. More recently, several studies have shown the benefits of maintenance therapy with Revlimid, thalidomide, Velcade, and dexamethasone.
In patients who are not eligible for autologous stem cell transplantation, low doses of melphalan can be added to the above mentioned combination therapy options. The reason why low-dose melphalan is not used upfront in patients being considered for autologous stem cell transplantation is that it can impair the ability to collect stem cells.
In addition to the drugs mentioned above, it is important that myeloma patients receive bisphosphonates such as Aredia (pamidronate) and Zometa (zoledronic acid) to decrease risk of skeletal events such as fractures.
Prognosis
The commonly used prognostic factors for multiple myeloma, such as staging, karyotype analysis, and fluorescence in situ hybridization (FISH) are also applicable to patients with nonsecretory disease. At our institution, we also routinely use a technique called gene expression profiling to determine prognosis and strategize treatment.
Although the nature and presentation of nonsecretory myeloma is different from secretory multiple myeloma, we do not see an overall difference in survival outcomes in this group of patients compared to the other patients with myeloma. However, it is useful to note that the patients with nonsecretory myeloma are less likely to have myeloma-related kidney damage.
A study from the Center for International Blood and Marrow Transplant Registry (CIBMTR) in patients treated between 1989 to 2003 demonstrated that patients with nonsecretory and secretory myeloma have similar outcomes with average survival time of about five years. I should note, however, that the widespread use of newer drugs such as Velcade, thalidomide, and Revlimid started after the period covered by the CIBMTR study. Thus, outcomes are likely better in patients who are currently undergoing treatment.
Secretory Myeloma Can Become Nonsecretory
It is important to note that patients who have secretory myeloma at the time of initial diagnosis may sometimes become nonsecretory at the time of relapse. Imaging techniques, such as PET and MRI, should therefore be considered when tracking response/remission status, even in patients with secretory disease.
Dr. Bijay Nair is an assistant professor of medicine at the University of Arkansas for Medical Sciences Myeloma Institute for Research and Therapy in Little Rock, Arkansas. His research focuses on developing new treatments for patients with relapsed and refractory myeloma. Dr. Nair writes a quarterly column for The Myeloma Beacon.
Dr Nair is our new doc in Arkansas. And I have a friend in Arkansas that is this type of patient. I appreciate a better understanding of this interesting presentation.
Question: is a non-secreting MM patient generally a high risk MM patient?
Lori,
Isn't the question you asked answered, indirectly, in the section of the article about prognosis? It says that:
"Although the nature and presentation of nonsecretory myeloma is different from secretory multiple myeloma, we do not see an overall difference in survival outcomes in this group of patients compared to the other patients with myeloma."
Presumably, if nonsecretory patients more often are high-risk myeloma patients, there would be a difference in survival outcomes between nonsecretory and secretory patients. But this doesn't seem to be the case.
Very helpful.
Great column! I know Dr. Nair well, and it's wonderful he is writing for the Beacon. He's able to make complex subjects understandable.
Thanks!
Mike,
Isn't there a difference for overall survival for high risk MM patients?
IOW's within the MM patient profile we have a high risk subset.
Could non-secretory also be high risk, even if the overall survival is the same as the MM population as a whole?
Just wondering.
Hi suzierose,
I know that the prognosis of high-risk patients varies a lot. But I think the point of the risk-based classification of myeloma patients, rather than the old staging approach, is to link the classification with average prognosis. So "high risk" patients, on average and by definition, do not have as good a prognosis as medium- and low-risk patients.
Dr. Nair says that the prognosis of nonsecretory patients is the same as secretory patients. So I'm guessing, and I admit it's a guess, that means that about the same share of nonsecretory and secretory patients are "high risk" at diagnosis.
I did dig a little deeper into this issue and found that there was an article here at the Beacon that is relevant. Here is a link to it:
http://www.myelomabeacon.com/news/2011/01/12/the-majority-of-rare-myelomas-are-associated-with-poorer-survival-than-common-myelomas/
The full text of the article it summarizes also is available online for free. Here is its link:
http://www.haematologica.org/content/early/2010/10/22/haematol.2010.022848.full.pdf
In this study, the researchers found that nonsecretory patients were a bit younger than secretory patients, but the main difference between the two groups was that secretory patients were noticeably more likely to have bone issues at diagnosis.
As a result, nonsecretory patients were more likely than secretory patients to be classified at diagnosis as Stage III.under the Durie-Salmon system. But, remember, that system is not a risk classification. It's a staging system.
And, in fact, nonsecretory patients in this study had a slightly better response to stem cell transplant, and a slightly longer overall survival, than secretory patients.
Thanks Mike,
That was really nice of you to look more in-depth.
Great info.
Thanks Mike.
Hi to everyone, maybe I can help answer the high risk question with nonsecretory MM. I have stage three nonsecretory MM but, I'm borderline high risk because of the type of MM I have. I'm probably going to say this a little wrong, it's IGa Kappa with a cromazone 13 deletion of the 16th segment ( never was good at chemistry). This is what my doc says is what makes me borderline not the nonsecretory part. It does make you constantly wonder how your doing, but you just keep on pushing on. For my doc the best way to know is alight chain test and bone marrow biopsies, 6 in the past yr. and a 1/2, and another coming in a month. In my case the biopsies seem to give the best reading and give me piece of mind. Thank you Dr. Nair, the article answered some of my questions.
Dr. Nair:
Thank you for a well presented and most informative primer on non-secretory MM.
This article is timely in that a newly diagnosed member of the local blood cancer support group (not a pt. at UAMS) shared this week that, while she falls into this classification, she doesn't know how to communicate her condition to others in practical terms. I have forwarded the article's link to her.
This is an example of what the Myeloma Beacon does best. It provides access to insightful information that benefits patients directly.
Thank you, Dr. Nair and the MB.
Full disclosure - Dr. Nair is my primary physician at UAMS, too. I am grateful to be in such good hands. I also know that all of the kind words that I say about him will not get me out of my bone marrow biopsy in a couple of weeks!
Cheers!
Dr. Nair is my Doctor and proud to say so. He is approachable and very good person as well as excellent care giver. Had me in remission in 10 months and now in maintenance mode. As long as I can keep from knowing cost I am OK. Keep up the great work UAMS.
Thank you for this empowering information. Recently diagnosed, at age 41 with NSMM, we have just started coming to terms with what now has to be faced and treated. Your clear professional understanding has both enlightened us about the disease, and brightened our general outlook with the knowledge that someone of your caliber is on our side. Maybe our paths will connect us further one day.
Thank you for such an informative article that I was able to (slmost) understand. My husband has been diagnosed with this disease. His blood lab test of blood and urine are all negative and in good order. No elevated protein levels at all were noted. The x rays of his bones were also negative for several years after initial diagnosis. Now he is in the hospital after a fall that broke several bones (two in the cervical area, and three in the pubic area). I asked the doc if a PET scan would be good for him. He replied that MM does not show up on PET scans. Now, I am confused. How should I proceed? What do I need to know? How best can I help?
Bibi, PET scans are one of the primary methods to discover and track MM. I'm having one on Monday.