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What is the benefit of treating SMM?
When should you begin treatment for smoldering multiple myeloma (SMM)? To put this question another way, what is the benefit of treating SMM?
In my experience as a long-term MM survivor, all conventional treatment is toxic and all toxic therapy has risks and benefits, pros and cons. What are the benefits of treating SMM?
The only benefit of beginning conventional treatment that the linked article below mentions is to prevent end-organ damage. Both MGUS and SMM do not exhibit end-organ damage.
The bullet points listed below all point to this one benefit of treatment for SMM- slowing the progression of SMM to full MM and therefore reducing the possibility of end-organ damage.
What is the benefit of conventional treatment of high-risk smoldering myeloma?
- Delayed Progression to Symptomatic Myeloma: Conventional treatment, including therapies like lenalidomide or dexamethasone, has been shown in studies to delay the time it takes for high-risk SMM to evolve into symptomatic myeloma. This postponement is important as it buys time and may prevent the complications associated with active disease, such as bone lesions, anemia, or renal failure.
- Improved Quality of Life: By intervening early and delaying the onset of MM-related symptoms, treatment can help patients avoid the debilitating effects of the disease, such as bone pain, fractures, fatigue, and organ damage, thus maintaining a better quality of life.
- Potential for Disease Control with Less Aggressive Therapy: Early intervention may allow for controlling the disease with less intensive treatments compared to the more aggressive treatments required when the disease progresses to full-blown myeloma. It also gives an opportunity to use novel agents in a less toxic regimen.
- Lower Risk of Organ Damage: The progression of myeloma can lead to organ damage, particularly affecting the kidneys and bones. Early treatment in high-risk SMM might mitigate this risk by controlling the abnormal plasma cell proliferation before it causes serious harm.
- Better Long-term Prognosis: Some studies have suggested that early treatment in patients with high-risk SMM may improve long-term survival outcomes by addressing the disease before it fully transforms into symptomatic myeloma, where prognosis tends to worsen.
- Avoidance of Emergency Situations: By treating high-risk SMM early, patients may avoid the risk of an acute emergency due to myeloma complications, such as severe anemia, bone fractures, or hypercalcemia, which can occur suddenly once MM becomes symptomatic.
My response to this one benefit is:
- All studies document that each and every SMM patent who begins treatment eventually progresses to full blown MM. All.
- All studies document that each SMM patient experience some side effects.
- I’ve never found a study that documents a longer overall survival aka length of life.
If you are a high-risk SMM patient considering active treatment consider:
- Some high-risk SMM will never progress to full MM
- Evidence-based non-conventional therapies can reduce your risk of a MM diagnosis
- Undergoing weeks or months of pre-habilitation, according to research, will enhance your response to treatment if you ever do undergo chemo
- Make sure that your health insurance will pay for all of your conventional therapies if you have SMM- remember SMM is not cancer, it is a blood disorder and may not be covered by your health insurance
If you are interested in learning more about evidence-based non-conventional therapies shown to reduce the risk of MM, email me at David.PeopleBeatingCancer@gmail.com
Thank you,
David Emerson
- MM Survivor
- MM Cancer Coach
- Director PeopleBeatingCancer
Smoldering Multiple Myeloma: Risk Factors, Who to Treat, How to Treat
It’s been almost 50 years since “monoclonal gammopathy of undetermined significance,” or MGUS, was identified as a precursor to multiple myeloma. Yet the debate over when and how to treat patients who have not developed the organ damage associated with the blood cancer is as lively as ever…
High-risk smoldering multiple myeloma (SMM) has emerged as the condition where treatment yields the greatest benefit, said S. Vincent Rajkumar, MD, professor of medicine at Mayo Clinic. These patients are biologically distinct from those with MGUS, and those with high-risk features should be treated, he explained.
“Initially it was thought that smoldering myeloma is some in-between stage, between MGUS and smoldering multiple myeloma. But that’s not what it is,” he said. “We now know that smoldering multiple myeloma is a heterogeneous clinical condition, clinically defined where one-third of the patients have high-risk smoldering myeloma. They actually have myeloma, but they don’t have the end organ damage, and two-thirds have MGUS.”
Citing recommendations published in 2022, he said that patients with SMM should undergo risk stratification; those with high-risk SMM should receive either lenalidomide or lenalidomide with dexamethasone for 2 years, or they should enroll in a clinical trial. High-risk patients are those that have a time to progression of 2 years or less, as defined by an algorithm he outlined. Others should be observed every 3 to 4 months.1
For those who say it’s better to wait for more trial data that compares early data to observation, Rajkumar said there’s not much more data on the way. He is an investigator in the AQUILA trial (NCT03301220), which is studying the use of subcutaneous daratumumab in patients high-risk smoldering multiple myeloma. “We will know the results soon. But after that, there are no more randomized trials with observation along ongoing,” he said.
For those who believe it’s possible to observe patients and catch progression before it happens, Rajkumar said, “At Mayo, we have found out this is easier said than done.” He reviewed results that showed the even at a top institution, “we miss the end organ damage 50% of the time….We want to prevent organ damage.”
Approaches to Risk Stratification. Irene Ghobrial, MD, who is senior vice president for Experimental Medicine, director of the Center for Early Detection and Interception of Blood Cancers, and co-leader of the Lymphoma/Myeloma Cancer Center Program at Dana-Farber Cancer Institute, discussed risk stratification in high-risk patients; in SMM, she said, progression of SMM is about 10% a year.
The question, she said, is how to differentiate between those who will progress—and need early treatment—from those who are “more MGUS-like.” She offered highlights from different models that have been developed to evaluate patient characteristics, and then discussed the elements to be evaluated, which include:
- Dynamic progression of monoclonal protein levels
- Circulating tumor cells
- Genomics and transcriptomics
- Immune and non-immune microenvironment
- Genetics and ancestry
Genomic aberrations can help define precursor conditions, and Ghobrial detailed studies that have used whole genome sequencing, circulating tumor cells, and other strategies to create models that can predict progression. One of the discoveries, she explained, is that the genome for multiple myeloma is present long before a patient presents with full-blown disease.
“By the time we have overt myeloma, it’s been there for 30 years,” she said. For smoldering myeloma, “by the time it’s progressing, it’s already very mature and has a lot of genomic aberrations. For MGUS [it’s] about 15 years.”
Ghobrial then discussed the immune microenvironment. “You cannot look only at the cancer cells without looking at the immune cells. “A few years ago, we asked the question whether, by single cell sequencing, [if] the immune system is altered. And we indeed found that even as early as MGUS, you find that those patients have compositional changes.”