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Smoldering Multiple Myeloma Treatment

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If you have been diagnosed with smoldering multiple myeloma (SMM), is your goal to slow a diagnosis of multiple myeloma or is your goal to live as long a life with as high a quality of life as possible?

Yes, according do several studies including the second study linked below, treating high-risk smoldering myeloma patients will, on average, delay the SMM patient’s progression to full multiple myeloma.

If you ask a high-risk smoldering multiple myeloma (SMM) patient if they will undergo low-dose therapy that should slow the progress of a diagnosis of full multiple myeloma, I think most will give an emphatic yes!

Why would you want to begin therapy?

  • Numerous studies show that treating high risk SMM will slow a diagnosis of MM

Why wouldn’t you want to begin therapy?

  • No study to date, has shown that treatment for SMM extends lives. Further, treatment is treatment meaning, treatment is toxic and toxic means side effects.
  • Evidence-based non-conventional therapies reduce your risk of multiple myeloma-
  • Evidence-based non-conventional therapies will “pre-habilitate” you-

Lastly, according to the American Cancer Society more than 96% of all newly diagnosed cancer patients are stage 2,3. Most MM patients don’t know they have MM and therefore don’t have it diagnosed.

SMM patients are different. If your SMM progresses to full MM, then you will be early MM aka MM stage 1. The standard-of-care therapy plan for MM is way too much toxicity for you in my experience.

Consider undergoing a small amount of chemo (low-dose revlimid?) and also supplementing with curcumin as well.Curcumin has been shown to enhance revlimid aka lenalidomide.



David Emerson

  • MM Survivor
  • MM Cancer Coach
  • Director PeopleBeatingCancer

Debate: Should Smoldering Myeloma Be Treated?

“A debate in Houston at the annual meeting of the Society of Hematologic Oncology tackled a vexing issue in hematology: Should smoldering myeloma be treated?…

In a poll after the debate, about a third of audience members agreed that watchful waiting is the way to go, but about two-thirds favored a personalized approach to smoldering myeloma treatment based on patient risk…

Meanwhile, treated patients in both trials had more adverse events, including secondary malignancies, and there’s the possibility that early treatment may make patients resistant to treatment later on when they progress to multiple myeloma, although that didn’t seem to happen in the Spanish trial…

Randomized Trial of Lenalidomide Versus Observation in Smoldering Multiple Myeloma

Purpose: Observation is the current standard of care for smoldering multiple myeloma. We hypothesized that early intervention with lenalidomide could delay progression to symptomatic multiple myeloma…

Lenalidomide was administered orally at a dose of 25 mg on days 1 to 21 of a 28-day cycle. The primary end point was progression-free survival, with disease progression requiring the development of end-organ damage attributable to multiple myeloma and biochemical progression…

Results: One hundred eighty-two patients were randomly assigned-92 patients to the lenalidomide arm and 90 to the observation arm. Median follow-up is 35 months.

Response to therapy was observed in 50%  of patients in the lenalidomide arm, with no responses in the observation arm. Progression-free survival was significantly longer with lenalidomide compared with observation. One-1, 2-, and 3-year progression-free survival was 98%, 93%, and 91% for the lenalidomide arm versus 89%, 76%, and 66% for the observation arm, respectively.

Only six deaths have been reported, two in the lenalidomide arm versus four in the observation arm.  Grade 3 or 4 nonhematologic adverse events occurred in 25 patients (28%) on lenalidomide.

Conclusion: Early intervention with lenalidomide in smoldering multiple myeloma significantly delays progression to symptomatic multiple myeloma and the development of end-organ damage.

Is aggressive treatment of smoldering myeloma the path to curing myeloma?

“The cumulative data from these studies should instill skepticism toward the hypothesis that early intervention with intensive treatment strategies in SMM is the optimal path to curing myeloma. Furthermore, these data should prompt us to challenge the utility and acceptance of uncontrolled studies of asymptomatic SMM.

This is especially true in the era of advanced diagnostics such as whole-body diffusion-weighted MRI that can be used longitudinally to identify focal lesions before the appearance of lytic lesions or fractures.

One prospective study that undertook active surveillance of SMM with serial MRIs and laboratory tests demonstrated that the vast majority of patients who progressed did so without morbid events such as fractures or renal failure.28

Dynamic risk scores that depend on multiple time-point tests will be needed to improve current risk-stratification systems and guide treatment initiation.12,29 Furthermore, the use of genomics that might predict, with greater accuracy, which patients are likely to progress to MM, will also aid in future decision making30-32 and pave the way for RCTs testing early intervention strategies in patients with genomically defined HR-SMM. Although the ongoing DETER-SMM trial (NCT03937635) will answer an important question, whether time-limited intensive treatment (daratumumab-lenalidomide-dexamethasone) improves OS when compared with low-intensity treatment (lenalidomide-dexamethasone) in patients with HR-SMM, it will remain unknown whether early therapeutic intervention improves OS compared with active surveillance in the modern era (ie, patients with contemporary HR-SMM followed with serial imaging). We, therefore, propose that an active surveillance strategy with advanced imaging should still be used as the control arm for RCTs testing early intervention in HR-SMM.

In smaller hypothesis-generating trials in which having a control arm may not be feasible, prespecified boundaries for treatment-related toxicity and death as well as QoL assessments should be incorporated. In addition, end points that account for death and morbid or symptomatic progression events such as pathologic fracture or irreversible renal failure should be captured in clinical trials to better identify therapeutic benefit of early intervention…”



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