Dr. Holstein is an Assistant Professor of Oncology at Roswell Park Cancer Institute, specializing in newly diagnosed and relapsed/refractory multiple myeloma. She has published several studies in peer-reviewed medical journals and her clinical research interests include development of novel therapeutic agents for multiple myeloma. Click here for Dr. Holstein’s bio.
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What is new in the treatment of MM besides chemo?
Dr. Holstein: This is a very exciting time for myeloma research. Small molecule drugs that target cell death pathways, signaling pathways, cell cycle pathways (just to name a few) are all under development. In addition, there are several different antibodies that are being tested in patients with myeloma, including antibodies which directly target cell surface markers on the myeloma cells and antibodies that target the growth factor that stimulates myeloma cell proliferation. There are several trials that are ongoing which are investigating how one’s immune system can be activated to combat the myeloma cells, including several vaccine trials and trials involving engineered T cells.
What is the longest remission period for post stem cell transplant multiple myeloma patients?
Dr. Holstein: The remission period after transplant remains extremely variable and difficult to predict. Some patients have achieved ten years of remission before their disease returns. The recent study published by my colleague, Dr. McCarthy, demonstrated that the median time to progression after transplant without maintenance therapy was 27 months compared with 46 months for those taking lenalidomide maintenance.
Are there any preventative treatment options for lytic lesions despite disease responding to Vel/rev/dex as evidenced by decreasing m spike, but due to kidney damage, cannot take bisphosphonates to prevent worsening of the lesions?
Dr. Holstein: It depends somewhat on the extent of kidney damage. Pamidronate can be given even for patients with a creatinine >3 (clearance <30), however a lower dose over a longer infusion time is recommended. In general, zoledronate is not given if the creatinine clearance is <30. It may however, be used at lower doses for less severe kidney damage. If there is significant kidney damage, it is best to talk with your kidney doctor to learn of their recommendations for calcium and vitamin D supplementation.
My doctor recommended a stem cell transplant for treatment of my stage 3 myeloma; I have a matched donor; should I consider an allogenic over an autologous transplant?
Dr. Holstein:At this time the standard of care remains an autologous stem cell transplant. Because allogeneic transplants are still associated with much higher morbidity and mortality than autologous stem cell transplants, allogeneic transplant is usually reserved for patients who have relapsed after autologous transplant and do not have other options for disease control.
I just completed a double stem cell transplant for stage 2 myeloma; is there any evidence that is should continue any kind of “maintenance” therapy?
Dr. Holstein:The Arkansas group has for many years now incorporated consolidation or maintenance treatment after double transplant as part of their total therapy approach to myeloma. One recent study that was presented last year randomized patients to receive either melphalan/lenalidomide/prednisone or double transplant. Then patients on each arm were again randomized to lenalidomide maintenance or no maintenance. Patients receiving lenalidomide maintenance had less chance of progressing from their disease. A survival benefit for maintenance therapy in this trial has not yet been found, but longer follow-up is needed. Given these results and the results of other trials showing benefit of maintenance therapy after single transplant, I would certainly consider the use of maintenance therapy after double transplant.
It seems as though there are so many drugs to treat myeloma now I am really confused. I have stage 3 disease and am 55; is there a “best” initial treatment?
Dr. Holstein:Although there is not consensus regarding the “best” initial treatment, many myeloma physicians prefer to use three-drug combinations for induction therapy such as RVD (Revlimid, Velcade, Dexamethasone) or CyBorD (Cytoxan, Velcade, Dexamethasone) in patients who are young and eligible for stem cell transplant. The choice of the regimen sometimes depends on factors such as kidney function, pre-existing neuropathy, travel distance to the chemotherapy infusion center, and cytogenetic risk factors. At this time, autologous stem cell transplant still remains a standard of care for younger patients.
I was going to get a double stem cell transplant when I get a second opinion the other doctor said I only needed a single transplant?
Dr. Holstein:The question of single vs. double transplant remains an area of contention amongst myeloma specialists. In a meta-analysis of studies that had been performed prior to 2008, it was found that: 1) double transplant is associated with an improved response rate; 2) double transplant is associated with an increase in transplant-related mortality; and 3) double transplant does not improve overall survival compared with single transplant. One of the problems of interpreting many of the prior studies is that they were done in the era before drugs such as lenalidomide and bortezomib were routinely used. I am eagerly awaiting the results of the BMT CTN 0702 trial which randomized patients to one of three arms: 1) tandem transplant plus lenalidomide maintenance, 2) single transplant plus consolidation with lenalidomide/bortezomib/dexamethasone followed by lenalidomide maintenance, or 3) single transplant plus lenalidomide maintenance because this study is most applicable to how patients get treated today. It should also be noted that depending on the insurance company or Medicare, often times only one transplant is covered. Unfortunately, because there is not yet consensus, it means that you will get different recommendations from different physicians. I am hoping the results of the BMT CTN 0702 trial will provide us with some answers.
Liquid Biopsy Detects Disease Progression Much Earlier Than Imaging
What if a simple blood test could quickly determine when chemotherapy was ineffective and prevent its unnecessary use?
Is it possible to have advanced myeloma when free light chain and SPEP/UPEP test are all normal? All blood work is normal.
Dr. Holstein:About 5% of newly diagnosed myeloma patients will have myeloma cells that do not secrete any abnormal protein, thus the free light chains, SPEP/UPEP can be normal. However, the bone marrow biopsy would confirm the presence of the malignant plasma cells. In this case, following the changes in the bone marrow over time is very important to document response to treatment.
How long do I have to live having multiple myeloma for 4 years now. What will happen to me as I run out of time? Has anyone ever beat this disease?
Dr. Holstein:While it has been very satisfying to see the improvement in average survival over the last decade, it still remains difficult to predict an individual patient’s outcome. Increasing understanding of patients’ disease based on cytogenetics and genome expression profiling are starting to allow us to more accurately predict survival, but unfortunately we still have a lot to learn about the biology of the disease.
With respect to what happens to a myeloma patient as their disease progresses—this is again variable and somewhat difficult to predict. Many times patients become progressively weaker and can have difficulty with infections. Some patients will experience kidney failure as a consequence of their disease. Fortunately, with the increasing number of treatment options available, patients are now receiving (and achieving benefit) from more treatments and are living longer with their disease.
It appears that a certain percentage of patients who undergo allogeneic stem cell transplant may be cured. In addition, long-term survivors (>10 years) have been reported after regimens containing autologous stem cell transplant.
How many MM patients and the number of years with quality of life (active lifestyle) are living in remission without chemo?
Dr. Holstein:The amount of time that a person stays in remission after transplant is still difficult for us to predict. Based on the recent study published by my colleague, Dr. McCarthy, the median time to progression after transplant without maintenance therapy was 27 months compared with 46 months for those taking lenalidomide maintenance. However, many times criteria for progression are met simply by increasing protein levels, but the patients continue to be asymptomatic from their disease. We refer to this as biochemical progression and oftentimes we simply monitor the patient. In this setting, we might be able to watch the patient for months to years before we have to put them back on chemotherapy. However, if there is evidence of new bone lesions, new plasmacytomas, or other evidence that the return of the myeloma is harming the body, then we will start the patient back on treatment.
Is high dose vitamin D advantageous with MM cancer?
Dr. Holstein:At this time there are not data supporting the use of high dose vitamin D in myeloma patients. We do know that vitamin D deficiency is common in the elderly and common in newly diagnosed patients. Correcting vitamin D deficiency is important for bone health and many patients are routinely placed on calcium/vitamin D supplementation.
I have IgG Kappa myeloma and had a SCT in May 2013. I’m currently on maintenance therapy of 10 mg rev. Since my SCT, my IgG levels have been low, hovering around 500. In February I received my first round of vaccinations. My last CBC revealed a rise in my IGg. Could these vaccines have contributed to the increase in my IgG?
Dr. Holstein:Typically the IgG level slowly rises after transplant. It could be that your vaccinations contributed somewhat to this increase, but it may also be your immune system slowly recovering. It is not unusual for IgG levels to be low one year out from transplant.
Can you explain in the response criteria: If the serum and urine M-protein are unmeasurable, a > 50% decrease in the difference between involved and uninvolved FLC levels is required.
Dr. Holstein:While the majority of patients have myeloma cells that secrete intact antibody (e.g., IgG, IgA) that can be measured on SPEP or UPEP, approximately 20% of patients have myeloma cells that secrete only light chain (either kappa or lambda). At very high levels the free light chains can be picked up on SPEP or UPEP, but at lower levels they can only be detected using the free light chain assay. This test measures the level of both kappa and lambda in the blood. As the absolute levels of both kappa and lambda can be affected by things such as kidney function, the response criteria calls for taking the difference between the two and using the change in that difference over time to measure response. If somebody has kappa light chain myeloma then kappa is their involved free light chain and lambda is their uninvolved free light chain. At time of diagnosis their kappa level would be much higher than there lambda level. After treatment, if the disease is responding, the kappa level should be close to equal to the lambda level.
My father died 10 years ago from multiple myeloma, do I have a risk of myeloma based on genetics?
Dr. Holstein:In general we do not view myeloma as a familial cancer. The epidemiology data do suggest that there is a slightly increased risk of myeloma if a first degree relative has myeloma. However, screening for myeloma in family members is not recommended. What I do recommend is for family members of myeloma patients to have age-appropriate cancer screening (e.g., mammograms, Pap smear, colonoscopy) and to have routine health maintenance check-ups with their primary care providers.
Is there any way to know how long multiple myeloma has been in your body prior to diagnosis? I am curious to know how long I have to make a decision about my treatment plan.
Dr. Holstein:The majority of patients diagnosed with myeloma have had the precursor condition MGUS (monoclonal gammopathy of undetermined significance) which is characterized by an increase in plasma cells and abnormal protein levels. The amount of time between appearance of MGUS and progression to myeloma is very variable, and may range from one to over 10-20 years. Once the diagnosis of active myeloma is made, the urgency with which treatment is started is based on factors such as overall health, impending or existing kidney damage, and high calcium levels.
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