The first 60 days: Smouldering multiple myeloma
Smouldering myeloma is myeloma that has not yet damaged bones, kidneys or blood counts. Most people are watched, but those at high risk of progressing can now be treated: the AQUILA trial showed daratumumab alone delays active myeloma, and it was approved for this use in 2025. Below, week by week, is what OnCo's record of Smouldering multiple myeloma says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
- RadiologistNamed in the standard of care for: Low- and intermediate-risk.
- Medical oncologistNamed in the standard of care for: High-risk (Mayo 20/2/20 or IMWG high risk), Trials of interception.
- Palliative and supportive care teamNamed in the standard of care for: High-risk (Mayo 20/2/20 or IMWG high risk).
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
Active monitoring with blood tests every three to six months and imaging when the M-protein or light chains rise; no treatment.
Daratumumab monotherapy for up to three years (AQUILA), or lenalidomide with or without dexamethasone (E3A06), or a clinical trial; monitoring remains acceptable after shared decision-making.
Bispecific antibodies (linvoseltamab), isatuximab-lenalidomide-dexamethasone and curative-intent quadruplets in high-risk disease; population screening studies.
LinvoseltamabIsatuximabA Study to Compare Linvoseltamab and Daratumumab Treatment in High-Risk Smoldering Multiple Myeloma (HR-SMM)A Proof-of-Concept Trial to Study the Safety and Activity of Linvoseltamab in Adult Participants With Smoldering Multiple Myeloma at High Risk of DeveIsatuximab in Combination With Lenalidomide and Dexamethasone in High-risk Smoldering Multiple MyelomaiStopMM
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Serum M-protein and immunofixation, Free light chain ratio, Marrow plasma cell percentage, Mayo 20/2/20 and IMWG risk scores, High-risk cytogenetics: t, del, gain 1q), and what were the results?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Recognised subtypes for this cancer include Low-risk smouldering myeloma, Intermediate-risk smouldering myeloma, High-risk smouldering myeloma.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Low- and intermediate-risk
- For my situation (low- and intermediate-risk), which of the standard options do you recommend and why?Guideline options include: Active monitoring with blood tests every three to six months and imaging when the M-protein or light chains rise; no treatment.
High-risk (Mayo 20/2/20 or IMWG high risk)
- For my situation (high-risk (mayo 20/2/20 or imwg high risk)), which of the standard options do you recommend and why?Guideline options include: Daratumumab monotherapy for up to three years (AQUILA), or lenalidomide with or without dexamethasone (E3A06), or a clinical trial; monitoring remains acceptable after shared decision-making.
- Am I a candidate for Daratumumab, Lenalidomide, Dexamethasone, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Trials of interception
- For my situation (trials of interception), which of the standard options do you recommend and why?Guideline options include: Bispecific antibodies (linvoseltamab), isatuximab-lenalidomide-dexamethasone and curative-intent quadruplets in high-risk disease; population screening studies.
- Am I a candidate for Linvoseltamab, Isatuximab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of A Study to Compare Linvoseltamab and Daratumumab Treatment in High-Risk Smoldering Multiple Myeloma (HR-SMM) and A Proof-of-Concept Trial to Study the Safety and Activity of Linvoseltamab in Adult Participants With Smoldering Multiple Myeloma at High Risk of Deve apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Any stage
- Are there clinical trials I could join, for example of Daratumumab, Linvoseltamab, Isatuximab, iStopMM?Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Supportive care improves quality of life and helps patients complete treatment.
- I read that “No trial has shown that treating smouldering myeloma lengthens life rather than delaying the label of active disease”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Risk models still misclassify many patients in both directions”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.
- A Study to Compare Linvoseltamab and Daratumumab Treatment in High-Risk Smoldering Multiple Myeloma (HR-SMM)Phase 3 · recruiting · NCT07393282A Phase 3, Randomized, Open-Label Study of Linvoseltamab Versus Daratumumab in Participants With Smoldering Multiple Myeloma at High Risk of Developing Multiple Myeloma
- Isatuximab in Combination With Lenalidomide and Dexamethasone in High-risk Smoldering Multiple MyelomaPhase 3 · active · NCT04270409A Phase 3 Randomized, Open-label, Multicenter Study of Isatuximab (SAR650984) in Combination With Lenalidomide and Dexamethasone Versus Lenalidomide and Dexamethasone in Patients With High-risk Smoldering Multiple Myeloma
- A Proof-of-Concept Trial to Study the Safety and Activity of Linvoseltamab in Adult Participants With Smoldering Multiple Myeloma at High Risk of DevePhase 2 · active · NCT05955508Phase 2 Study of Linvoseltamab in Patients With Smoldering Multiple Myeloma at High Risk of Progression to Multiple Myeloma
- iStopMMPhase observational · active · NCT03327597Population screening of Icelanders over 40 for MGUS with randomised follow-up strategies
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Smouldering multiple myeloma: the full pageSmouldering myeloma is myeloma that has not yet damaged bones, kidneys or blood counts. Most people are watched, but those at high risk of progressing can now be treated: the AQUILA trial showed daratumumab alone delays active myeloma, and it was approved for this use in 2025.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- Smouldering myeloma / MGUS: Early plasma-cell conditions with no organ damage; most never progress, but high-risk smouldering disease is now sometimes treated.
- R-ISS / R2-ISS staging: R-ISS is the myeloma staging system, combining blood markers with high-risk chromosome changes to predict outcome.
- High-risk cytogenetics (myeloma): Chromosome changes such as del(17p), t(4;14), t(14;16) and extra copies of 1q that mark myeloma likely to relapse early.
Every term links to the glossary.