Is blood donation risky for patients with MGUS?

Is blood donation risky for patients with MGUS?

We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

Monoclonal gammopathy of unknown significance (MGUS) is often considered a pre-cancerous condition.

Blood donors with MGUS are typically advised to discontinue blood donation as their blood may be risky for blood recipients.

This paradigm has been recently challenged (e.g. La Raia 2015), but also reinforced (e.g. Felldin 2016).

It is also possible that blood donation may be risky for donors with MGUS as well, as it leads to an overall boost and stimulation in hematopoiesis which may indirectly favor prograssion from MGUS to myeloma.

Is it true?

From MGUS to Multiple Myeloma, a Paradigm for Clonal Evolution of Premalignant Cells

Multiple myeloma (MM) is a treatable, but incurable, malignancy of plasma cells (PC) in the bone marrow (BM). It represents the final stage in a continuum of PC dyscrasias and is consistently preceded by a premalignant phase termed monoclonal gammopathy of undetermined significance (MGUS). The existence of this well-defined premalignant phase provides the opportunity to study clonal evolution of a premalignant condition into overt cancer. Unraveling the mechanisms of malignant transformation of PC could enable early identification of MGUS patients at high risk of progression and may point to novel therapeutic targets, thereby possibly delaying or preventing malignant transformation. The MGUS-to-MM progression requires multiple genomic events and the establishment of a permissive BM microenvironment, although it is generally not clear if the various microenvironmental events are causes or consequences of disease progression. Advances in gene-sequencing techniques and the use of serial paired analyses have allowed for a more specific identification of driver lesions. The challenge in cancer biology is to identify and target those lesions that confer selective advantage and thereby drive evolution of a premalignant clone. Here, we review recent advances in the understanding of malignant transformation of MGUS to MM. Cancer Res 78(10) 2449–56. ©2018 AACR.

Blood Glucose, MGUS, Metformin and Myeloma: Part 2

I first heard about metformin as a possible treatment for multiple myeloma from Dr. Robert Orlowski with MD Anderson, a myeloma specialist, who was a co-author of a paper on the topic published in The British Journal of Cancer. Generally, as with other cited evidence, the BJC paper indicated worse outcomes for diabetic myeloma patients, but also showed that treatment of such patients with metformin was associated with better results. Beyond that there was other evidence that persons who had myeloma and were taking metformin regularly seemed to experience disease progression more slowly than others. Data shows that myeloma patients with diabetes, are associated with shorter survival, although research by Wu et al. (2014) seems to indicate that metformin ameliorated that risk. There is also recent research showing that metformin may have potential therapeutic use in treating myeloma. Recent data from Zi et al. (2014) showed a direct effect of metformin against myeloma in vivo with Dexamethasone. There is even recent research suggesting Metformin increases the effectiveness of Bortezomib (Velcade) as recently described in research summarized by Jagganathan et al. (2015).

Metformin and Ritonavir as Potential Therapeutic Agents

As we described last time, there is some evidence (albeit inconclusive) that metformin may slow progression of MGUS and myeloma with conventionally used agents such as Dexamethsone and Bortezomib (Velcade). However, there is also intriguing data over the last few years showing that metformin when matched with another drug, ritonavir, routinely used to treat HIV, may have beneficial anti-myeloma impacts. In 2012, Dr. Steven T. Rosen, then at Northwestern University was working towards a clinical trial to test this drug combination. And the research paper describing the rationale for the trials is here. And more recently, Dalva-Adyemir et al. (2015) – with Rosen one of the authors-- again showed research suggesting possible effectiveness of ritonavir and metformin along with strong justification for its mode of action. Ritonavir capitalizes on a key myeloma plasma cell malignancy characteristic: that of elevated glucose utilization which is intrinsic to the survival and proliferation of myeloma cells. Many myeloma patients who have had a PET (positron emission tomography) scan are aware that radioactive glucose is used in the test as the plasma cells have an elevated glucose uptake and may then become visible to sensitive whole body scans for concentrations of radioactivity. But unlike healthy cells, myeloma cells depend strongly on certain types of glucose uptake. Myeloma researchers have determined that myeloma clones depend heavily on glucose transporter-4 (GLUT4) for supporting their gluttonous glucose habit. This is where FDA approved protease inhibitor ritonavir comes in: it elicits a selective inhibitory effect on GLUT4. Metformin, on the other hand, inhibits mitochondrial complex 1 which GLUT4 impaired plasma cells seek to exploit to survive in the presence of ritonavir. When subjected to both therapies in combination, the hope is that myeloma cells will be killed outright (apoptosis) or otherwise severely inhibited. The combination of metformin and ritonavir becomes a sort of 1-2 punch to starve myeloma from its mode of unrestrained replication. Dr. Rosen has now filed a patent on GLUT4 inhibitors for blood cancers including multiple myeloma. So what to make of all this? Should myeloma patients be running out to start taking metformin? No. We embrace evidence-based medicine. The evidence is not yet conclusive. Within treating myeloma, the medical research community seeks to protect us from flawed and ineffective treatment as well as over treatment. Approved medical treatment for myeloma needs to be based on the proven ability of treatments to help us more than they might harm us. And this needs to be proven in randomized clinical trials in a statistically convincing fashion, ideally replicated in different settings, patient populations and by different researchers. This is the foundation of evidence-based medicine. And as myeloma patients, we should be very grateful to the tireless genetic scientists, myeloma researchers and oncologists who seek to bring its power and safety to our treatment. For a moment, let’s go back to the compelling research from the Chang et al. (2015). This work shows an almost undeniable association in the difference in the progression of diabetic MGUS patients to myeloma depending on whether they are taking metformin or not. However, a key thing about MGUS patients is that this problem is common whereas only about 10% of these patients will develop myeloma over their lifetime. Remembering the Hippocratic Oath—do no harm-- the risk to treat such a massive population, often unnecessarily, could far outweigh the benefits. On the other hand if one is an MGUS patient with high serum blood glucose, then seeing an endocrinologist to prescribe metformin might be a reasonable course of action—particularly if the MGUS was classified as the high risk variety. However, to recommend taking metformin as a high risk MGUS patient would require rigorous clinical trials and not just cohort studies or case-control evaluations of the type I have cited in preceding weeks.

Proving Anti-Myeloma Drugs Work: Why it’s so Hard

Nature does not give up its secrets easily. This is particularly true with complex systems. What’s a complex system? That person in the mirror: a human being. As many of you know, I have spent many hours looking at cohort, meta-analysis and case-control studies looking at all kinds of issues associated with diet and myeloma. These data are sparse enough and hardly rigorous. I know the dangers so these studies and at least try not to cherry pick them. I’m not interested in pseudoscience, nor should you be. The anti-vaccination movement tills that territory. A big difference for me and my examination of influences of diet and myeloma: you remain a flexible attitude towards evidence in lieu of definitive clinical trials. And you know that while you are trying to exploit beneficial associations in the existing data, you can’t be sure of whether the recommendations will help. “The science is soft,” as Dr. Jeff Wolf, my myeloma specialist says. However, I still believe it is still useful to try to exploit evidence on how we might help ourselves. Most often, such studies are all we have. And it is quite true that I tend to pay attention when there are multiple studies pointing to the same factors (cruciferous vegetables, ursolic acid-rich foods and fish appear helpful to the reducing chance of developing myeloma, while sugar and butter do not). Of course, we hardly know if the same factors might be useful for people that already have myeloma Today we hear the repeated warning to would be data miners: correlation does not imply causality. And that caution is pounded into the skulls of budding statisticians in graduate schools everywhere. I heard it plenty too-- and it is fair warning. But one also does well to listen to the sage advice of Edward Tufte: “Correlation is not causation,” he counsels,” but it sure is a hint.” In other words, more studies and independent reviews of the same phenomenon by multiple sources showing correlation is a powerful hint that there may be causality lurking about. But while correlation is necessary for causation, the opposite is not true. Still, consistent evidence of correlation with studied variables versus a parameter of interest compels us to look further. And we should look if maintaining a skeptical stance. And even well-trained doctors and diagnostic experts can be swayed by large numbers of cohort studies and a consistent chain of evidence. Back when I began to work on this series, I spoke with Dr. Vincent Rajkumar, arguably one of the preeminent myeloma researchers today. As a cautionary tale, the good doctor told me about work he did back in 1997 where he and colleagues had many studies showing the hormone replacement therapy looked to be helpful for women to reduce their chances of cardiac events. He and colleagues composed a paper based on the cutting edge research were they recommended such therapy be routinely recommended for post-menopausal women. They were confident the recommendations would help and potentially save lives. But they were wrong. Completely wrong. A follow-up randomized study by the Women’s Health Initiative not only showed hormone replacement therapy was not helpful to reduce cardiac events, but, in fact, the opposite was true. It was unhelpful. Only a true randomized trial was able to reveal that bias in the opportunity samples was hiding the truth of the matter. I was impressed by Dr. Rajkumar’s candor and my enthusiasm for showing the link between blood glucose, metformin and myeloma greatly slowed the composition of this series. Why? While the evidence on blood glucose, diabetes and metformin is intriguing, it is hardly definitive. There might be other hidden factors at work. What to do? On this, statistician George Box was aptly paraphrased: “The only way to find out what will happen when a complex system is disturbed is to disturb the system, not merely to observe it.” Randomized clinical trials where the treatment is disturbed relative to the group receiving it and lurking confounding variables are randomly distributed across groups So, how to establish causality in a sea of cohort and case control studies? While there are now several studies pointing to metformin having large potential impacts on MGUS or myeloma, although intriguing they are not definitive. I think we can readily agree that the human body is a complex system, so the recommendation is to carefully design experiments and randomize subjects so that the influences are randomized in a particular way so that we can find out what effects are truly caused by the factors of interest. And then to also use some of the other means to combat statistical bias: randomized studies conducted by other researchers and on different populations and with good sample sizes. Will metformin help with efficacy of our conventional treatments such as Dexamethasone and Velcade? And will metformin and ritonavir turn out to be another treatment in the growing pharmacological arsenal against myeloma? Or another failed drug combination of many to have not been proven in the difficult arena of rigorous clinical trials? We can’t know. I just wanted those of us in the myeloma world to understand the difficult challenge our doctors and medical researchers face. Thank them, would you?

What to do While we Wait?

What to do while we wait for more definitive data on whether metformin or ritonavir might be possible treatments for us? Firstly, we watch and use the other FDA approved drugs becoming available under guidance of our doctors to help ourselves. But clearly, from my perspective, it seems prudent for myeloma patients to watch their blood glucose carefully—and to keep an eye on clinical trials and other developments regarding metformin and myeloma. If your blood glucose is high and you have myeloma or MGUS, it might be advisable to see an endocrinologist. You can also help yourself without metformin: none of your doctors will complain about your personal efforts to control your blood glucose through diet and exercise. Even if not a magic bullet, there is ever more data showing that this is likely a good idea for those of us suffering multiple myeloma. Indeed, it is a good idea for just about everyone on the planet in the Western World where the risk for obesity and Type 2 diabetes seems to grow each year. In particular, recent rigorous clinical trials published in the Lancet have shown that individuals embracing a Mediterranean diet, with foods such as olive oil, whole grains and leafy vegetables and fruits, have a lower risk of developing diabetes. In the study, complex carbohydrates foods such as oat cereal, yogurt and low-fat dairy products, green leafy vegetables, grapes, apples, blueberries and walnuts and limited alcohol consumption were associated with reduced diabetes risk. Drinking coffee and even decaffeinated coffee were also associated with lower type 2 diabetes risk. And the unhelpful foods? Sodas and other sugary drinks, red and processed meats and refined carbohydrates. Candy, ice cream and pastries. And particularly bad would be heavy carbohydrates and sugars eaten on an empty stomach. Disaster for breakfast? glazed donuts…or pancakes with lots of syrup And there is a lot of data to suggest that exercise is important in helping to control blood sugar as experienced within Type 2 diabetes. I just picked out a recent meta-study. There are many. The main enemy?-- sedentary lifestyle. More important than the type of exercise appears to just be the choice of exercise versus surrender to the coach potato life. So, not only watch your diet, but in consultation with your doctors, get out and move! Me? Walking is always good-- fresh air and a new perspective. And, while I haven’t seen a study yet (it’ll be coming), I’d bet daily walkers have better mental health too… Oh, it has been done! Spanish office workers who are regular walkers report better sense of well-being: Who could be surprised? Be well everyone. And thanks for your patience and attention while I try to make my case that blood glucose could be important to us.

Sjögren Patients with Highly Active Disease at Risk of Condition with Ties to Blood Cancer, Study Says

Monoclonal gammopathy, a condition marked by an unusual protein produced in plasma cells and one that can progress to a blood cancer, is evident in patients with Sjögren syndrome and certain other rheumatic diseases, a Chinese study found.

Sjögren patients with highly active disease are more likely to develop this disorder, the researchers added.

Monoclonal gammopathy (MG) of unknown significance is characterized by the presence of an abnormal antibody-related protein (M protein) in the blood, produced by the immune cells that normally produce antibodies.

In most cases, monoclonal gammopathy is considered a benign condition. B ut in rare cases it can progress to certain blood cancers, including multiple myeloma, Waldenström macroglobulinemia, and lymphoma.

MG can also be associated with rheumatic diseases such as Sjögren syndrome, but its role in the development of malignancies in these patients is controversial. Previous research found an increased risk of lymphoma in rheumatic patients with MG, but findings regarding a myeloma risk are unclear.

Researchers in China examined the clinical manifestations, disease activity, and the prevalence of blood cancers in patients with rheumatic diseases and MG, with the goal of identifying clinical clues for risk factors linking monoclonal gammopathy and cancer that might aid in early diagnosis.

The study included 41 patients hospitalized at the Peking University People’s Hospital in Beijing. All were diagnosed with a rheumatic disease and with MG, after testing for the M protein in the blood and urine, from 2010 to 2017.

Rheumatic disorders in these patients included Sjögren syndrome — the most common, diagnosed in 12 people or 29% of the 41 patients — rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis.

Most patients had abnormal laboratory analysis related to a problematic immune system: high erythrocyte sedimentation rate (ESR) , inversion of the albumin/globulin (A/G) ratio , positivity for rheumatoid factors (RF) , hypergammaglobulinemia , and hypocomplementemia (low levels of complement factors, elements of the immune system).

Researchers also compared Sjögren’s patients with MG to those without this condition.

Both groups were identical in clinical manifestations, but patients with MG more often showed troubling levels of an enzyme in their urine known as NAG , an indicator of kidney damage had higher levels of erythrocyte sedimentation rate, and greater disease activity, as measured by the EULAR Sjögren Syndrome Disease Activity Index ( ESSDAI ) and Clinical ESSDAI ( ClinESSDAI ) scores. Both are standard tools for assessing disease activity in primary Sjögren syndrome patients.

Analysis revealed that high disease activity, irrespective of the score used to assess it, was the only independent risk factor for the presence of MG.

Seven (17.1%) of the 41 Sjögren-MG patients also had a blood cancer. The most common was multiple myeloma (four people), followed by smoldering multiple myeloma in two patients, and one case of B-cell lymphoma of mucosa-associated lymphoid tissue (MALT).

The presence of M proteins’ “light-chain” in the blood was significantly linked with an increased risk of multiple myeloma but not of other blood cancers. The small number of patients in this group limited finding of more risk factors, the researchers noted.

“The presence of MG seems associated with higher disease activity of the underlying autoimmune process,” they wrote.

Given the presence of blood cancers in a considerable proportion of patients with MG, researchers recommend screening for MG and closely monitoring Sjögren and other rheumatic disease patients for possible cancer development.

“To facilitate an early diagnosis and timely intervention, we recommend the inclusion of MG screening in patients with rheumatic disorders especially when they exhibit a phenotype with high ESR, A/G inversion, RF positivity, hypergammaglobulinemia, hypocomplementemia, or renal injury of unknown reasons,” the team concluded.

Medical Conditions Affecting Donation

Certain medications may delay your ability to donate blood. If you are taking any medication, even if it is not listed here, please call the Blood Donor Room at 212-639-7643 to determine your eligibility.

Accept after resolved and treatment completed

Accept if benign, if malignant accept one year after treatment completed

Acceptable after condition resolved and treatment completed

Accept if recovered and renal function normal

Accept if benign, if malignant defer one year after treatment completed

Accept if asymptomatic and not taking replacement therapy

Accept if recovered and asymptomatic

Accept if treatment completed & feeling well. Defer for 90 days if untreated

Aortic or cerebral, if surgically corrected and asymptomatic, defer for 6 months from date of surgery. If not surgically corrected, a letter of medical clearance is needed

Acceptable 3 months after last symptom with a letter of medical clearance from physician

Defer if cause is genetic. Accept if stable and symptom free

Accept 6 months after procedure if donor is asymptomatic, has no limitations on activity and has a letter of medical clearance

Domestic pets- accept if wound is healed

Defer for one year if exposed to any animal&rsquos blood through a needle stick

Defer until full course of treatment is completed

Antiphospholipid Antibody syndrome

Accept 6 months after surgical repair if donor is asymptomatic and has no limitations on activity

A donor with a history of arrhythmia can be accepted if asymptomatic, has no history of other cardiac problems and has a letter of medical clearance

Arteriovenous (AV) Malformation

Accept if surgically corrected and asymptomatic for 6 months from date of surgery. If not surgically corrected, a medical clearance is needed

Accept (both osteoarthritis and rheumatoid arthritis)

If causing permanent lung disease-permanent deferral, otherwise accept

Accept if asymptomatic, has no history of other cardiac problems and has a letter of medical clearance

BCG (Bacillus Calmette Guerin)

Defer for 2 weeks after treatment with BCG

Benign Prostatic Hypertrophy (BPH)

Accept if benign. Defer 2 weeks after treatment with BCG

Defer for 8 weeks from marrow harvest

Accept if no chronic renal disease

Accept if treatment completed and feeling well. If untreated, defer 90 days

Defer 5 years after completion of treatment, with no recurrence for any history of leukemia, lymphoma, myeloma or Hodgkin&rsquos Disease

No deferral period for localized skin cancer (basal or squamous cell and melanoma in-situ) if completely excised and healed

Defer one year after treatment is completed for other cancers in remission

Acceptable after completion of treatment for papillary thyroid carcinoma

Carcinoma-in-situ of the vulva, cervix or breast

Acceptable after completion of treatment

Acceptable after 6 months, if asymptomatic with letter of medical clearance from physician

Accept 6 months with a letter of medical clearance from physician

Accept 6 months from last symptom with a letter of medical clearance from physician

Accept if a simple fracture. If surgery, defer until cast removed and healed

Accept after resolved and treatment completed

Defer unless evaluated by MD and not due to heart disease

If not previously immunized or infected, defer 4 weeks after exposure. Defer 4 weeks from active infection

Accept one month after recovery

If diagnosed by a MD-permanent deferral

Coagualtion Factor Deficiencies

Permanent deferral except for Factor XII (12) deficiency

Permanent deferral if disseminated or extrapulmonary. If pulmonary, defer 1 year after diagnosis provided treatment is complete

Accept if dry and healing

Defer for active symptoms of a cold, flu or upper respiratory infection and for 3 days after symptoms have subsided

Defer for 3 days after last episode of diarrhea

Collagen Vascular Diseases

Accept if asymptomatic with no limitation of activity. If surgically corrected, accept after 6 months if asymptomatic with no limitation of activity

Accept 6 months from last symptom resolved with a letter of medical clearance from physician

Contrast for medical imaging

Accept if no seizure in the past month

Coronary artery bypass surgery

Accept 6 months after surgery if donor is asymptomatic with no limitation on activity and has a letter of medical clearance. If due to a heart attack, accept one year later if asymptomatic with no limit on activity and with a letter of medical clearance

Defer 14 days from positive test and/or and resolution of symptoms

Accept if recovered and no jaundice occurred

Accept if asymptomatic and no diarrhea for 3 days

Accept if asymptomatic. Permanent deferral if extrapulmonary

Accept if asymptomatic and off treatment

Accept if no current respiratory infection

Accept after resolved and treatment completed

Accept if resolved and at least one month after completion of anticoagulant therapy

Common Reasons People Can't Donate

If you don’t feel well on the day of your donation, please call to cancel. We’ll be happy to see you 24 hours after your symptoms pass.

Most medications will not disqualify you from being able to donate blood, but may require a waiting period after your final dose.

If you were unable to donate due to low iron, you may still be able to donate in the future. The Red Cross recommends taking steps to help increase your iron level.

You may be deferred from donating blood or platelets if you have lived in or traveled to a malaria-risk country in the past three years.


Survival in multiple myeloma has improved significantly in the last 15 years. 49 The initial impact came from the introduction of thalidomide, 50 bortezomib, 51 and lenalidomide. 52, 53 In the last decade, carfilzomib, pomalidomide, panobinostat, ixazomib, elotuzumab, daratumumab, isatuximab, and selinexor have been approved by the Food and Drug Administration (FDA) for the treatment of relapsed multiple myeloma, and promise to improve outcomes further. Numerous combinations have been developed using drugs that have shown activity in multiple myeloma, and the most commonly used regimens are listed in Table 6. 54-76 These drugs work through a variety of mechanisms, some of which are not fully understood. Thalidomide, lenalidomide, and pomalidomide are termed immunomodulatory agents (IMiDs)they bind to cereblon and activate cereblon E3 ligase activity. This results in the rapid ubiquitination and degradation of two specific B cell transcription factors, Ikaros family zinc finger proteins Ikaros (IKZF 1) and Aiolos (IKZF3). 77-79 They may cause direct cytotoxicity by inducing free radical mediated DNA damage. 80 They also have anti-angiogenic, immunomodulatory, and tumor necrosis factor alpha inhibitory properties. Bortezomib, carfilzomib, and ixazomib are proteasome inhibitors. 81-83 Elotuzumab targets SLAMF7 daratumumab and isatuximab target CD38 respectively. 71, 84-86 Panobinostat is a deacetylase inhibitor. 73, 87

Thalidomide 200 mg oral days 1-28

Dexamethasone 40 mg oral days 1, 8, 15, 22

Lenalidomide 25 mg oral days 1-21 every 28 days

Dexamethasone 40 mg oral days 1, 8, 15, 22 every 28 days

Pomalidomide 4 mg days 1-21

Dexamethasone 40 mg oral on days on days 1, 8, 15, 22

Bortezomib 1.3 mg/m 2 subcutaneous days 1, 8, 15, 22

Melphalan 9 mg/m 2 oral days 1-4

Prednisone 60 mg/m 2 oral days 1 to 4

Bortezomib 1.3 mg/m 2 subcutaneous days 1, 8, 15, 22

Thalidomide 100-200 mg oral days 1-21

Dexamethasone 20 mg oral on day of and day after bortezomib (or 40 mg days 1, 8, 15, 22)

Repeated every 4 wk × 4 cycles as pre-transplant induction therapy

Cyclophosphamide 300 mg/m 2 orally on days 1, 8, 15 and 22

Bortezomib 1.3 mg/m 2 subcutaneous on days 1, 8, 15, 22

Dexamethasone 40 mg oral on days on days 1, 8, 15, 22

Repeated every 4 wk c c The day 22 dose of all three drugs is omitted if counts are low, or after initial response to improve tolerability, or when the regimen is used as maintenance therapy. When used as maintenance therapy for high risk patients, further delays can be instituted between cycles.

Bortezomib 1.3 mg/m 2 subcutaneous days 1, 8, 15

Lenalidomide 25 mg oral days 1-14

Dexamethasone 20 mg oral on day of and day after bortezomib (or 40 mg days 1, 8, 15, 22)

Repeated every 3 wk d d Omit day 15 dose if counts are low or when the regimen is used as maintenance therapy. When used as maintenance therapy for high risk patients, lenalidomide dose may be decreased to 10-15 mg per day, and delays can be instituted between cycles as done in total therapy protocols.

Carfilzomib 20 mg/m 2 (days 1 and 2 of cycle 1) and 27 mg/m 2 (subsequent doses) intravenously on days 1, 2, 8, 9, 15, 16

Cyclophosphamide 300 mg/m 2 orally on days 1, 8, 15

Dexamethasone 40 mg oral on days on days 1, 8, 15, 22

Carfilzomib 20 mg/m 2 (days 1 and 2 of cycle 1) and 27 mg/ m 2 (subsequent doses) intravenously on days 1, 2, 8, 9, 15, 16

Lenalidomide 25 mg oral days 1-21

Dexamethasone 40 mg oral days 1, 8, 15, 22

Carfilzomib 20 mg/m2 (days 1 and 2 of cycle 1) and 27 mg/m2 (subsequent cycles) intravenously on days 1, 2, 8, 9, 15, 16

Pomalidomide 4 mg oral on days 1-21

Dexamethasone 40 mg oral on days on days 1, 8, 15, 22

Daratumumab 16 mg/kg intravenously weekly × 8 wk, and then every 2 wk for 4 months, and then once monthly

Lenalidomide 25 mg oral days 1-21

Dexamethasone 40 mg intravenous days 1, 8, 15, 22 (given oral on days when no daratumumab is being administered)

Lenalidomide-Dexamethasone repeated in usual schedule every 4 wk

Daratumumab 16 mg/kg intravenously weekly × 8 wk, and then every 2 wk for 4 months, and then once monthly

Bortezomib 1.3 mg/m 2 subcutaneous on days 1, 8, 15, 22

Dexamethasone 40 mg intravenous days 1, 8, 15, 22 (given oral on days when no daratumumab is being administered)

Bortezomib-Dexamethasone repeated in usual schedule every 4 wk

Daratumumab 16 mg/kg intravenously weekly × 8 wk, and then every 2 wk for 4 months, and then once monthly

Pomalidomide 4 mg oral on days 1-21

Dexamethasone 40 mg intravenous days 1, 8, 15, 22 (given oral on days when no daratumumab is being administered)

10 mg/kg intravenously weekly × 8 wk, and then every 2 wk

Lenalidomide 25 mg oral days 1-21

Dexamethasone per prescribing information

Lenalidomide-Dexamethasone repeated in usual schedule every 4 wk

Ixazomib 4 mg oral days 1, 8, 15

Lenalidomide 25 mg oral days 1-21

Dexamethasone 40 mg oral days 1, 8, 15, 22

Panobinostat 20 mg oral three times a week × 2 wk

Bortezomib 1.3 mg/m 2 subcutaneous days 1, 8, 15

10 mg/kg intravenously weekly × 8 wk, and then 20 mg/kg every 4 wk

Pomalidomide 4 mg oral days 1-21

Dexamethasone per prescribing information

Lenalidomide-Dexamethasone repeated in usual schedule every 4 wk

10 mg/kg intravenously weekly × 4 wk, and then every 2 wk

Pomalidomide 4 mg oral days 1-21

Dexamethasone per prescribing information

Pomalidomide-Dexamethasone repeated in usual schedule every 4 wk

Selinexor 100 mg/kg oral once weekly

Dexamethasone 20 mg oral twice weekly

  • a All doses need to be adjusted for performance status, renal function, blood counts, and other toxicities.
  • b Doses of dexamethasone and/or bortezomib reduced based on other data showing lower toxicity and similar efficacy with reduced doses dose of selinexor reduced based on better tolerability with once weekly dosing in subsequent randomized trial subcutaneous route of administration of bortezomib preferred based on data showing lower toxicity and similar efficacy compared to intravenous administration.
  • c The day 22 dose of all three drugs is omitted if counts are low, or after initial response to improve tolerability, or when the regimen is used as maintenance therapy. When used as maintenance therapy for high risk patients, further delays can be instituted between cycles.
  • d Omit day 15 dose if counts are low or when the regimen is used as maintenance therapy. When used as maintenance therapy for high risk patients, lenalidomide dose may be decreased to 10-15 mg per day, and delays can be instituted between cycles as done in total therapy protocols.
  • e Carfilzomib can also considered in a once a week schedule of 56 mg/m 2 on days 1, 8 and 15 every 28 days (cycle 1, day 1 should be 20 mg/ m 2 ) day 8, 9 doses of carfilzomib can be omitted in maintenance phase of therapy after a good response to improve tolerability KCd dosing lowered from that used in the initial trial which was conducted in newly diagnosed patients.

The approach to treatment of symptomatic newly diagnosed multiple myeloma is outlined in Figure 1 and is dictated by eligibility for ASCT and risk-stratification. The data to support their use from recent randomized trials using new active agents for multiple myeloma are provided in Table 7. 38, 39, 88, 89 In order to initiate therapy, patients must meet criteria for multiple myeloma as outlined in Table 1. Early therapy with lenalidomide and dexamethasone or single-agent lenalidomide is beneficial in patients with high risk smoldering multiple myeloma, and is discussed separately. 90, 91 There is an ongoing “cure versus control” debate on whether we should treat multiple myeloma with an aggressive multi-drug strategy targeting complete response (CR), or a sequential disease control approach that emphasizes quality of life as well as OS. 92, 93

Trial Regimen Number of patients Overall response rate (%) CR plus VGPR (%) Progression-free survival (median in months) P value for progression free survival Overall survival (median in months) a a Estimated from survival curves when not reported.
P value for overall survival
Durie et al 38 Rd 229 72 32 31 .002 64 .025
VRd 242 82 43 43 75
Attal et al 39 VRd 350 97 77 36 NR 82% at 4 y .87
VRd-ASCT 350 98 88 50 <.001 NR 81% at 4 y
Facon et al 88 Rd 369 81 53 32 NR N/A
DRd 368 93 79 NR 71% at 30 mo <.001 NR
Moreau et al 89 VTd 542 90 78 NR 85% at 18 mo <.001 NR 90% at 30 mo <.05
Dara-VTd 543 90 83 NR 93% at 18 mo NR 96% at 30 mo
  • Abbreviations: ASCT, autologous stem cell transplantation CR, complete response Dara-VTd, daratumumab, bortezomib, thalidomide, dexamethasone DRd, daratumumab, lenalidomide, dexamethasone N/A, not available Rd, lenalidomide plus dexamethasone VGPR, very good partial response VRd, bortezomib, lenalidomide plus dexamethasoneVTd, bortezomib, thalidomide, dexamethasone.
  • a Estimated from survival curves when not reported.

Recent data show that MRD negative status (as estimated by next generation molecular methods or flow cytometry) has favorable prognostic value. 30 However, additional trials are needed to determine if changes in treatment need to be made based on MRD status. At present, MRD results are recommended mainly as a prognostic metric and not for used in making treatment decisions. We also need additional data to determine if MRD negativity can be used as a surrogate endpoint for regulatory approval, and if sustained MRD negativity may be a marker of cure in at least a subset of patients. 32

5.1 Initial treatment in patients eligible for ASCT

Typically, patients are treated with approximately 3-4 cycles of induction therapy prior to stem cell harvest. After harvest, patients can either undergo frontline ASCT or resume induction therapy delaying ASCT until first relapse. There are many options for initial therapy, and the most common treatment regimens are discussed below. These regimens can also be used at the time of relapse. In general, the low-dose dexamethasone regimen (40 mg once a week) is preferred in all regimens to minimize toxicity. In a randomized trial conducted by the Eastern Cooperative Oncology Group (ECOG), the low-dose dexamethasone approach was associated with superior OS and significantly lower toxicity. 56

5.1.1 Triplet regimens

Bortezomib, lenalidomide, dexamethasone (VRd) is the current standard of care for newly diagnosed multiple myeloma. In a randomized trial conducted by the Southwest Oncology Group (SWOG), response rates, PFS, and OS were significantly superior with VRd compared with Rd (Table 7). 38 Stem cell collection with granulocyte stimulating factor (G-CSF) alone may be impaired when lenalidomide is used as induction therapy. 94 Patients who have received more than 4-6 cycles of lenalidomide may need plerixafor for stem cell mobilization. All patients treated with lenalidomide require anti-thrombosis prophylaxis. Aspirin is adequate for most patients, but in patients who are at higher risk of thrombosis, either low-molecular weight heparin or warfarin is needed. 95-97 If lenalidomide is not available for use as initial therapy or in the presence of acute renal failure, other bortezomib-containing regimens such as bortezomib-thalidomide-dexamethasone (VTd) or bortezomib-cyclophosphamide-dexamethasone (VCd) can be used instead of VRd. A recent randomized trial found that VTd results in superior response rates compared with VCd, but impact on long-term outcomes is not known. 98 Therefore both are reasonable alternatives to VRd. Daratumumab, lenalidomide, dexamethasone (DRd) has shown significant activity in patients who are not candidates for transplantation, and is an additional alternative to VRd. 88

In initial studies, peripheral neuropathy was a major concern with bortezomib therapy. Neuropathy with bortezomib can occur abruptly, and can be significantly painful and debilitating. However, the neurotoxicity of bortezomib can be greatly diminished by administering bortezomib once a week instead of twice-weekly, 59, 60 and by administering the drug subcutaneously instead of the intravenous route. 99 The once-weekly subcutaneous bortezomib schedule (Table 6) has made serious neuropathy an uncommon problem, and has made regimens such as VRd, VCd, and VTd much more tolerable. Bortezomib does not appear to have any adverse effect on stem cell mobilization. 100

Two phase II trials reported results with carfilzomib when used in combination with lenalidomide and dexamethasone for newly diagnosed multiple myeloma. 101, 102 However, there is concern for greater risk of serious toxicity with carfilzomib, and more data are needed. A randomized trial in the United States (referred to as the ENDURANCE trial) is currently ongoing comparing VRd vs KRd as initial therapy.

5.1.2 Quadruplet regimens

Quadruplet regimens containing daratumumab, a monoclonal antibody targeting CD38 are showing promise. In one randomized trial, daratumumab, bortezomib, thalidomide, dexamethasone (Dara-VTd) showed superior response rates, progression-free survival (PFS), and a trend to better OS compared with VTd. 89 A randomized phase II trial found that the addition of daratumumab to VRd increases the rate and depth of response to therapy. 103 In these trials, as expected, the benefit of daratumumab in terms of surrogate endpoints was more pronounced in the standard risk patients, a positive effect was nevertheless seen in both standard and high risk disease. Phase III data on the incremental PFS and OS benefit with quadruplet regimens over the current standard of VRd is awaited. Therefore, it is prudent to restrict the use of quadruplet regimens to transplant eligible patients with high risk double or triple hit myeloma, until we have clear OS data to justify adding potential long-term costs and risks to standard risk patients who currently have excellent outcomes with the VRd triplet. Trials with other quadruplet regimens are ongoing. A randomized trial to determine the patient subset that can benefit most from quadruplets is also expected to open soon in the United States.

5.1.3 Multi-drug combinations

Besides the regimens discussed above, other options include anthracycline-containing regimens such as bortezomib, doxorubicin, dexamethasone (PAD) 40 or multi-agent combination chemotherapy regimens, such as VDT-PACE (bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide). 104, 105 These regimens are particularly useful in patients with aggressive disease such as plasma cell leukemia or multiple extramedullary plasmacytomas. Several other regimens have been tested in newly diagnosed multiple myeloma, but there are no clear data from randomized controlled trials that they have an effect on long-term endpoints compared with the regimens discussed earlier.

5.1.4 Recommendations

  • In standard-risk patients eligible for ASCT, I favor VRd as initial therapy for 3-4 cycles, followed by ASCT and lenalidomide maintenance therapy. In patients who are tolerating therapy and responding well, an alternative is VRd for 8 to 12 cycles followed by lenalidomide maintenance therapy. In such patients stem cells must be collected for cryopreservation after the first 3-4 cycles of VRd, and ASCT must be considered at first relapse.
  • In high-risk patients, especially those with double-hit or triple-hit myeloma, I favor Dara-VRd as initial therapy for 3-4 cycles followed by ASCT and then bortezomib-based maintenance (eg, bortezomib every 2 weeks, or a low intensity VRd regimen).
  • In patients presenting with acute renal failure suspected to be secondary to light-chain cast nephropathy, I prefer VCd or VTd as initial therapy in conjunction with plasma exchange (or dialysis with high-cut-off filter). Plasma exchange is continued daily until the serum FLC levels are less than 50 mg/dL and then repeated as needed till chemotherapy is fully effective.
  • In patients presenting with plasma cell leukemia or multiple extramedullary plasmacytomas, I prefer VDT-PACE as initial therapy followed by ASCT and then maintenance with a bortezomib-based regimen.
  • Once weekly subcutaneous bortezomib is preferred in most patients for initial therapy, unless there is felt to be an urgent need for rapid disease control.
  • Dexamethasone 40 mg once a week (low-dose dexamethasone) is preferred in most patients for initial therapy, unless there is felt to be an urgent need for rapid disease control.

5.2 Initial treatment in patients not eligible for ASCT

In patients with newly diagnosed multiple myeloma who are not candidates for ASCT due to age or other comorbidities, the major options for initial therapy are VRd and DRd. Although melphalan-based regimens have been extensively tested in these patients, they are not recommended due to concerns about stem cell damage and secondary myelodysplastic syndrome and leukemia. In the United States transplant eligibility is not determined by a strict age cut-off, and many patients enrolled in the melphalan-based clinical trials would be considered candidates for ASCT.

5.2.1 Bortezomib-based regimens

Therapy with VRd has shown a survival benefit compared with Rd, and is the preferred choice for initial therapy in patients who are not candidates for ASCT (Table 7). 38 So, VRd is administered for approximately 8-12 cycles, followed by maintenance therapy. In patients in whom initial therapy with VRd is not possible mainly for logistical reasons (such as problems with compliance due to need for parenteral administration), ixazomib can be considered in place of bortezomib. In frail elderly patients, a lower dose of lenalidomide should be used dexamethasone may be started at 20 mg once a week, then reduced as much as possible after the first 4-6 cycles, and discontinued after the first year.

5.2.2 DRd

Note, DRd has been recently approved for patients with newly diagnosed myeloma, based on the results of an international multicenter randomized trial. 88 PFS at 30 months was higher with DRd compared to Rd, 70.6% vs 55.6%, P < .001. MRD negative rates were also superior, 24.2% vs 7.3%, P < .001. DRd is an alternative to VRd in this setting. However, unlike VRd where the triplet regimen is only used for a limited duration, therapy with DRd requires treatment with all three drugs until progression which makes this a much more expensive regimen in the long-term. 106

5.2.3 Alkylator-based regimens

Melphalan-based regimens are considered only if there are problems with access to lenalidomide. Even in these situations, the risks of melphalan can be reduced by using cyclophosphamide instead, and studies show this substitution does not alter efficacy. 107 Thus, the VCd regimen can be considered as a minor modification of the VMP regimen, in which cyclophosphamide is used as the alkylating agent in place of melphalan. This variation has the advantage of not affecting stem cell mobilization, and dosing is more predictable. A randomized trial found superior PFS and OS with a four-drug regimen of Dara plus VMP compared with VMP in a randomized phase III trial, but the contribution of the fourth drug to the induction component cannot be ascertained from this trial. 108

5.2.4 Recommendations

  • In standard-risk patients, I prefer VRd as initial therapy administered for approximately 8-12 cycles, followed by lenalidomide maintenance. DRd is an alternative to VRd but adds cost and toxicity of long-term triplet therapy.
  • In high-risk patients, I favor VRd as initial therapy for approximately 8-12 cycles followed by bortezomib-based maintenance (eg, bortezomib every 2 weeks, or a low intensity VRd regimen).

5.3 Hematopoietic stem cell transplantation

5.3.1 Autologous stem cell transplantation (ASCT)

ASCT improves median OS in multiple myeloma by approximately 12 months. 109-112 However, randomized trials found similar OS with early ASCT (immediately following four cycles of induction therapy) vs delayed ASCT (at the time of relapse as salvage therapy). 113-115 A trial by the Intergroupe Francophone du Myelome (IFM) compared early vs delayed ASCT in patients treated with VRd followed by lenalidomide maintenance. 39 Patients were randomized to receive either VRd (three cycles) followed by ASCT and then VRd consolidation (two cycles) vs VRd × eight cycles with ASCT reserved for relapse. Both arms received lenalidomide maintenance for 1 year. A significant improvement in PFS was seen as expected with early ASCT, but this has so far not translated into a difference in OS (Table 7). Based on these results, it is reasonable to consider a delayed ASCT in patients with standard-risk multiple myeloma who prefer such an approach for personal and logistic reasons.

The role of tandem (double) ASCT is unclear. In earlier randomized trials, an improvement in OS was seen in two studies, 116, 117 but other studies failed to show such an improvement. 118, 119 More recent data are available from two other randomized trials are also inconclusive. In a trial conducted in Europe, an improvement in PFS and OS was seen with tandem ASCT in both standard and high risk patients. 120 However, no survival benefit has been seen so far in a randomized trial, conducted in the United States by the Bone Marrow Transplantation Clinical Trials Network (BMT-CTN), in standard or high risk multiple myeloma (BMT-CTN 0702 trial). 121 The US trial more likely reflects the impact of tandem ASCT in the context of modern therapy when most new options for salvage are available. Thus routine tandem ASCT is not recommended outside of a clinical trial setting.

5.3.2 Post-transplant consolidation

Consolidation therapy is a term used for the administration of a short course of therapy, usually with two or more drugs, prior to the start of long-term maintenance. The BMT-CTN 0702 trial had an arm that investigated the benefit of post-transplant consolidation therapy, followed by lenalidomide maintenance vs lenalidomide maintenance alone. 121 In this trial, additional cycles of VRd chemotherapy administered as consolidation after ASCT did not result in significant benefit. Unlike earlier trials, the BMT-CTN 0702 trial specifically isolated the effect of consolidation and is therefore more compelling than trials where one could not ascertain the precise added value of consolidation therapy on PFS and OS. Consolidation therapy after ASCT is not recommended and patients should proceed to standard low-intensity maintenance therapy.

5.3.3 Allogeneic transplantation

The role of allogeneic and non-myeloablative-allogeneic transplantation in multiple myeloma is controversial with studies showing conflicting results. 122, 123 The treatment related mortality (TRM) rate (10%-20%) and GVHD rates are fairly high. 124 Although allogenic transplantation should still be considered as investigational, it may be a consideration for young patients with high-risk disease, who are willing to accept a high TRM and the unproven nature of this therapy for a chance at better long-term survival.

5.3.4 Recommendations

  • ASCT should be considered in all eligible patients. But in standard-risk patients responding well to therapy, ASCT can be delayed until first relapse provided stem cells are harvested early in the disease course.
  • Tandem ASCT is not recommended outside of clinical trials
  • Allogeneic transplantation as frontline therapy should be considered investigational.

5.4 Maintenance therapy

Maintenance therapy is indicated following ASCT. Maintenance therapy should also be considered in following completion of 8-12 cycles of initial therapy in patients treated without ASCT. Lenalidomide is the standard of care for maintenance therapy for most patients. 125-130 In a meta-analysis of randomized trials, a significant improvement in PFS and OS was seen with lenalidomide maintenance compared with placebo or no therapy. 131 Lenalidomide maintenance is associated with a 2-3-fold increase in the risk of second cancers and patients must be counseled in this regard and monitored.

The impact of lenalidomide maintenance in patients with high risk multiple myeloma is unclear. In a meta-analysis, no significant OS benefit was seen in these subsets of high risk patients. 131 However, in a more recent trial that was not part of the meta-analysis, benefit was seen in high risk patients. 132 Bortezomib administered every other week has been shown to improve OS, particularly in patients with del(17p). 128 Bortezomib-based maintenance is preferable for high-risk patients. This can either consist of bortezomib alone given every other week, or low intensity VRd, to capture the effect of bortezomib and lenalidomide. 133 In patients unable to access or tolerate bortezomib, ixazomib is a reasonable alternative that has shown benefit in a placebo controlled randomized trial. 134

Among patients who did not undergo upfront ASCT, based on the results of the SWOG trial, maintenance therapy with lenalidomide should be considered in patients who are in good performance status after completion of initial 8-12 cycles of triplet therapy.

Although the benefit of maintenance is now established, data on optimal duration are lacking. We also need to consider the cost, toxicity, and inconvenience of long-term indefinite maintenance therapy. Many patients seek a drug-free interval. An ECOG trial is comparing lenalidomide maintenance given until progression vs a limited duration of 2 years. Trials are also examining if the duration of maintenance can be modified based on MRD results.

5.4.1 Recommendations

  • I recommend lenalidomide maintenance for standard-risk patients following ASCT. I also recommend lenalidomide maintenance following 8-12 cycles of VRd among patients who did not receive ASCT as part of initial therapy.
  • I recommend maintenance with bortezomib alone or low intensity VRd for patients with high-risk multiple myeloma.

MGUS & SMM Reduce Risk of Progression to Multiple Myeloma

A diagnosis of pre-myeloma, SBP, MGUS or SMM isn’t necessarily worrisome by itself. It is the possibility of a diagnosis of full-blown multiple myeloma (MM) that causes fear, anger and depression. At least my pre-myeloma diagnosis did for me back in early 1994.

What if you could undergo evidence-based, non-toxic therapies shown to reduce the risk of MM?

Even if you have been diagnosed with either MGUS or SMM you may not have the diagnostic information about your pre-multiple myeloma to be able to determine your risk of progression to MM.

And even if you are able to determine your risk of progression to MM, experience has shown me that evidence-based, non-toxic therapies can reduce your risk of progression to MM. Please understand, I did everything my oncologist told me to do and I still relapsed and reached end-stage MM. Back in the fall of 1997.

My experience is that conventional oncology just doesn’t understand pre-multiple myeloma- AKA

  • Single bone plasmycytoma (SBP)
  • Monoclonal Gammopathy of Undetermined Significance (MGUS)
  • Smoldering Multiple Myeloma (SMM)

I’ve included the information in the studies linked and excerpted below in this post because it gives you a sense of where the understanding is about the risk of pre-mm becoming full mm in 2011.

MGUS at a glance- click the illustration below:

  • Diagnostic Testing- Blood, Bone, Imaging
  • Symptoms- Bone Pain,Nerve Pain, Kidney Damage, Skin Rash,Blood Clot
  • Diagnosis, Prognosis- Risk of Progression to Multiple Myeloma, “Comparatively Lower Life-Expectancy”
  • Risk Factors- Lifestyle,Pesticides, Human PapillomaVirus, Relatives with MM/MGUS

If you do not want to “watch and wait” to see if your MGUS/SMM progresses to Multiple Myeloma please watch the short video below:

Consider MGUS Therapies such as:

  1. non-toxic, cytotoxic/apoptotic supplements,
  2. foods that starve MGUS/SMM and MM
  3. evidence-based mind-body therapies,
  4. detoxification therapies,
  5. Non-conventional bone health therapies

David Emerson

  • MM Survivor
  • MM Cancer Coach
  • Director PeopleBeatingCancer

Recommended Reading:

“Monoclonal gammopathy of unknown significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic plasma cell dyscrasias, with a propensity to progress to symptomatic MM.

In recent years there have been improvements in risk stratification models (involving molecular markers) of both disorders, which have led to better understanding of the biology and probability of progression of MGUS and SMM.

In the context of numerous molecular events and heterogeneous risk of progression, developing individualized risk profiles for patients with MGUS and SMM represents an ongoing challenge that has to be addressed by prospective clinical monitoring and extensive correlative science.

In this review we discuss the current standard of care of patients with MGUS and SMM, the use of risk models, including flow cytometry and free-light chain analyses, for predicting risk of progression. Emerging evidence from molecular studies on MGUS and SMM, involving cytogenetics, gene-expression profiling, and microRNA as well as molecular imaging is described. Finally, future directions for improving individualized management of MGUS and SMM patients, as well as the potential for developing early treatment strategies designed to delay and prevent development of MM are discussed…

Predicting progression with current clinical risk models-

The Mayo Clinic risk stratification model for MGUS identifies 3 major risk factors for progression:

  • non-IgG isotype,
  • serum M-protein concentration > 1.5 g/dL, and
  • a skewed FLC-ratio (normal reference: 0.26-1.65).19

At 20 years of follow-up, absolute risk of progression for MGUS patients with 0, 1, 2, and 3 risk factors is

For SMM, risk factors for progression include

  • bone marrow plasma cells > 10%,
  • serum M-protein concentration > 3 g/dL, and
  • a skewed FLC-ratio (normal reference: 0.125-8.0)

Cumulative risk of progression at 10 years for SMM patients with 1, 2, and 3 risk factors is:

Curcumin for the prevention of progression in monoclonal gammopathy of undetermined significance: A word of caution

“A recent pilot study found that curcumin, in certain patients with monoclonal gammopathy of undetermined significance (MGUS), decreases the paraprotein load and the urinary N-telopeptide of type 1 collagen bone turnover marker…

Best Food for MGUS to Prevent Multiple Myeloma

Multiple myeloma is one of our most dreaded cancers. It’s a cancer of our antibody-producing plasma cells, and is considered one of our most intractable blood diseases. The precursor disease is called monoclonal gammopathy of undetermined significance (MGUS). When it was named, it’s significance was undetermined, but now we know that multiple myeloma is almost always preceded by MGUS. This makes MGUS one of the most common premalignant disorders, with a prevalence of about 3% in the older white general population, and about 2 to 3 times that in African-American populations.

MGUS itself is asymptomatic, you don’t even know you have it until your doctor finds it incidentally doing routine bloodwork. But should it progress to multiple myeloma, you only have about four years to live. So, we need to find ways to treat MGUS early, before it turns into cancer. Unfortunately, no such treatment exists. Rather, patients are just placed in a kind of holding pattern with frequent check-ups. If all we’re going to do is watch and wait, researchers figured they might as well try some dietary changes.

One such dietary change is adding curcumin, the yellow pigment in the spice turmeric. Why curcumin? It’s relatively safe, considering that it has been consumed as a dietary spice for centuries. And, it kills multiple myeloma cells. In my video Turmeric Curcumin, MGUS, & Multiple Myeloma, you can see the unimpeded growth of four different cell lines of multiple myeloma. We start out with about 5000 cancer cells at the beginning of the week, which then doubles, triples, and quadruples in a matter of days. If we add a little bit of curcumin, growth is stunted. If we add a lot of curcumin, growth is stopped. This is in a petri dish, but it is exciting enough to justify trying curcumin in a clinical trial. And six years later, researchers did.

We can measure the progression of the disease by the rise in blood levels of paraprotein, which is what’s made by MGUS and myeloma cells. About 1 in 3 of the patients responded to the curcumin with dropping paraprotein levels, whereas there were no responses in the placebo group. These positive findings prompted researchers to commence a double-blind, randomized, controlled trial. The same kind of positive biomarker response was seen in both MGUS patients, as well as those with so-called “smoldering” multiple myeloma, an early stage of the cancer. These findings suggest that curcumin might have the potential to slow the disease process in patients, delaying or preventing the progression of MGUS to multiple myeloma. However, we won’t know for sure until longer larger studies are done.

The best way to deal with multiple myeloma is to not get it in the first place. In my 2010 video Meat & Multiple Myeloma, I profiled a study suggesting that vegetarians have just a quarter the risk of multiple myeloma compared to meat-eaters. Even just working with chicken meat may double one’s risk of multiple myeloma, the thinking being that cancers like leukemias, lymphomas, and myelomas may be induced by so-called zoonotic (animal-to-human) cancer-causing viruses found in both cattle and chickens. Beef, however, was not associated with multiple myeloma.

There are, however, some vegetarian foods we may want to avoid. Harvard researchers reported a controversial link between diet soda and multiple myeloma, implicating aspartame. Studies suggest french fries and potato chips should not be the way we get our vegetables, nor should we probably pickle them. While the intake of shallots, garlic, soy foods, and green tea was significantly associated with a reduced risk of multiple myeloma, intake of pickled vegetables three times a week or more was associated with increased risk.

For dietary links to other blood cancers, see EPIC Findings on Lymphoma.

The turmeric story just never seems to end. I recommend a quarter teaspoon a day:

  • Back to Our Roots: Curry and Cancer
  • Carcinogenic Blocking Effects of Turmeric
  • Turmeric Curcumin Reprogramming Cancer Cell Death
  • Turmeric Curcumin and Colon Cancer
  • Topical Application of Turmeric Curcumin for Cancer
  • Striking with the Root: Turmeric Curcumin & Ulcerative Colitis
  • Who Shouldn’t Consume Curcumin or Turmeric?
  • Turmeric Curcumin for Prediabetes

Why might garlic and tea help? See Cancer, Interrupted: Garlic & Flavonoids and Cancer Interrupted, Green Tea.

More on the effects of NutraSweet in Aspartame and the Brain and acrylamide in Cancer Risk From French Fries.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Michael Greger M.D. FACLM

Michael Greger, M.D. FACLM, is a physician, New York Times bestselling author, and internationally recognized professional speaker on a number of important public health issues. Dr. Greger has lectured at the Conference on World Affairs, the National Institutes of Health, and the International Bird Flu Summit, testified before Congress, appeared on The Dr. Oz Show and The Colbert Report, and was invited as an expert witness in defense of Oprah Winfrey at the infamous "meat defamation" trial.


Speaking Tour

Catch up with Dr. Greger at one of his live speaking engagements:

Speaking Tour Update

Given the level of reported community transmission and the prospects of flattening the pandemic curve by preventing unnecessary public gatherings, I’m postponing my speaking tour until we have a better handle on the prevalence and spread after sufficient testing is completed.

Risk of Progression from Precursor Disease to Symptomatic Myeloma

It is clear from the description above that there are no major genetic differences between the plasma cells in MGUS and multiple myeloma. Since the prevalence of MGUS/SMM is much higher than multiple myeloma, and several people with precursor disease will never progress to symptomatic myeloma in their lifetime, it is important to identify patients that are at greatest risk for progression to myeloma. Several studies have tried to predict subgroups of precursor disease at higher risk of progression using different tools.

Size of M protein

In 1,384 patients with MGUS, the risk of progression to multiple myeloma or a related disorder after 20 years was 14% with an initial protein level of 0.5 g/dL or less, 25% for 1.5 g/dL, 41% for 2 g/dL, 49% for 2.5 g/dL, and 64% for 3 g/dL (52). A progressive increase in the M-protein in the first year of follow-up (evolving MGUS) has also shown to be prognostic (53).

Type of immunoglobulin

Patients with MGUS with IgM or IgA monoclonal protein have an increased risk of progression to disease as compared with patients with IgG protein (52).

Serum-free light-chain ratio and the Mayo Clinic model

In a study of 1,148 patients with MGUS, Rajkumar and colleagues showed that an abnormal free light-chain (FLC) assay was an independent risk factor for progression from MGUS to multiple myeloma (54). For patients with MGUS, a non-IgG isotype, M-protein concentration more than 1.5 g/dL, and an abnormal FLC ratio are considered adverse prognostic factors. At 20 years, the risk of progression in patients with 0, 1, 2, and 3 risk factors is 5%, 21%, 37%, and 58%, respectively (Table 3). For patients with SMM, an M-protein ≥ 3 g/dL, an FLC ratio outside the range of 0.125 to 8, and ≥ 10% plasma cells in the bone marrow are considered as adverse factors in this model (55, 56). The 5-year rate of progression in patients with 1, 2, and 3 risk factors was 25%, 51%, and 76%, respectively (Table 5). Recently, Rajkumar and colleagues have proposed that SMM with more than 60% plasma cells progresses to multiple myeloma within 2 years in 95% cases and should be treated at diagnosis even in the absence of symptoms (57).

Risk stratification model for MGUS using Mayo Clinic model (54)

Flow cytometry and the Spanish model

Perez-Persona and colleagues used immunophenotyping with multiparameter flow cytometry to identify aberrant plasma cell (aPC) in the bone marrow of 407 MGUS and 93 SMM patients (58). A ratio of aPC/BMPC of more than 95% was shown to be an independent risk factor for progression in both MGUS and SMM. In a multivariate analysis, DNA aneuploidy (hypo- or hyperdiploidy) was also noted to be a prognostic factor in MGUS and was combined with aPC/BMPC of more than 95% to form a prognostic index. The presence of 0, 1, or 2 of these factors was associated with a progression risk of 2%, 10%, and 46%, respectively, in MGUS (Table 4). The analysis identified immunoparesis as an independent prognostic factor in SMM. Using aPC/BMPC of more than 95% and immunoparesis as the 2 factors the study found 5-year risk of 4%, 46%, and 72% in patients with 0, 1, or 2 factors, respectively (Table 6).