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Newly diagnosed multiple myeloma, transplant-eligible: the decisions you may face

4 treatment settings, 4 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.

Daratumumab plus bortezomib, lenalidomide and dexamethasone (PERSEUS) for four to six cycles; isatuximab-VRd or daratumumab-VTd (CASSIOPEIA) are alternatives.

The options, in plain words

The CD38 antibody that turned triplets into quadruplets: adding it to standard induction roughly halves the risk of myeloma progressing.

Bortezomib was the first proteasome inhibitor: it jams the cell's protein-recycling machine, which antibody-factory plasma cells cannot tolerate.

Lenalidomide is a thalidomide descendant that glues the proteins IKZF1 and IKZF3 to cereblon so the cell destroys them, killing plasma cells and rousing T cells. It is the backbone of myeloma treatment and maintenance, also used in mantle cell and follicular lymphoma, and generic since 2022.

Dexamethasone is a long-acting glucocorticoid steroid that kills lymphoid cancer cells directly, which is why it sits in nearly every myeloma regimen and in childhood leukaemia and lymphoma protocols. It is also the standard drug for preventing chemotherapy sickness and for brain swelling and spinal cord compression; high blood sugar, insomnia, muscle wasting and infection follow prolonged use.

Isatuximab is Sanofi's CD38 antibody, approved in frontline transplant-ineligible myeloma (IMROZ) and, from July 2026, as an under-the-skin injection.

The evidence behind it
The main trade-offs on record
  • Start at 0.7 mg/m² in moderate or severe impairment.
  • Dose by creatinine clearance: 10 mg daily for CrCl 30-60, 15 mg every other day below 30, 5 mg daily on dialysis.
Questions to ask about this decision
  1. Between Daratumumab, Bortezomib, Lenalidomide and the other options, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. How closely do I match the people in PERSEUS, and does that change what the results mean for me?
    Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
  4. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  5. Does your recommendation follow the current guideline (NCCN Guidelines: Multiple Myeloma), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  6. For my situation (induction), which of the standard options do you recommend and why?
    Why: Guideline options include: Daratumumab plus bortezomib, lenalidomide and dexamethasone (PERSEUS) for four to six cycles; isatuximab-VRd or daratumumab-VTd (CASSIOPEIA) are alternatives.
  7. Am I a candidate for Daratumumab, Bortezomib, Lenalidomide or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  8. How do the results of PERSEUS apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Add these to your appointment list, or take the full question set for this cancer.

Other settings

Consolidation

2 options

High-dose melphalan with autologous stem cell transplant, early or deferred to first relapse after stem cell collection; tandem transplant considered in high-risk disease.

The options, in plain words

The myeloma chemotherapy that is also the standard high-dose conditioning before autologous transplant, and, delivered directly into the liver's blood supply or the eye, treats uveal melanoma metastases and retinoblastoma.

Autologous stem cell transplant collects the patient's own blood-forming stem cells, gives melphalan or another chemotherapy at a dose that would otherwise destroy the marrow, then returns the cells to rebuild it. It is standard consolidation in myeloma and for relapsed lymphoma, though CAR-T has displaced it in early-relapsing large B-cell lymphoma.

  • Permits dose intensity impossible otherwise
  • Decades of outcome data
  • Widely available
The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record
  • Treatment-related mortality ~1-2% (myeloma) to higher in children
  • Infertility, second malignancies, prolonged cytopenias
  • Being challenged by CAR-T and MRD-guided deferral
Questions to ask about this decision
  1. Between Melphalan (including hepatic delivery system) and Autologous stem cell transplant (high-dose therapy), which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  4. Does your recommendation follow the current guideline (NCCN Guidelines: Multiple Myeloma), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  5. For my situation (consolidation), which of the standard options do you recommend and why?
    Why: Guideline options include: High-dose melphalan with autologous stem cell transplant, early or deferred to first relapse after stem cell collection; tandem transplant considered in high-risk disease.
  6. Am I a candidate for Melphalan (including hepatic delivery system), and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Add these to your appointment list, or take the full question set for this cancer.

Lenalidomide until progression; daratumumab added after daratumumab-based induction (PERSEUS); bortezomib-containing maintenance in high-risk disease; MRD-guided stopping in trials.

The options, in plain words

Lenalidomide is a thalidomide descendant that glues the proteins IKZF1 and IKZF3 to cereblon so the cell destroys them, killing plasma cells and rousing T cells. It is the backbone of myeloma treatment and maintenance, also used in mantle cell and follicular lymphoma, and generic since 2022.

The CD38 antibody that turned triplets into quadruplets: adding it to standard induction roughly halves the risk of myeloma progressing.

Bortezomib was the first proteasome inhibitor: it jams the cell's protein-recycling machine, which antibody-factory plasma cells cannot tolerate.

The evidence behind it
The main trade-offs on record
  • Dose by creatinine clearance: 10 mg daily for CrCl 30-60, 15 mg every other day below 30, 5 mg daily on dialysis.
  • Start at 0.7 mg/m² in moderate or severe impairment.
Questions to ask about this decision
  1. Between Lenalidomide, Daratumumab and Bortezomib, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. How closely do I match the people in PERSEUS, and does that change what the results mean for me?
    Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
  4. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  5. Does your recommendation follow the current guideline (NCCN Guidelines: Multiple Myeloma), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  6. For my situation (maintenance), which of the standard options do you recommend and why?
    Why: Guideline options include: Lenalidomide until progression; daratumumab added after daratumumab-based induction (PERSEUS); bortezomib-containing maintenance in high-risk disease; MRD-guided stopping in trials.
  7. Am I a candidate for Lenalidomide, Daratumumab, Bortezomib, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  8. How do the results of PERSEUS apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Add these to your appointment list, or take the full question set for this cancer.

Other settings

Response assessment

4 options

M-protein and free light chains every cycle, MRD by sequencing or flow cytometry after transplant and during maintenance, imaging for residual focal lesions.

The options, in plain words

Sequencing the unique genetic barcode of a patient's leukaemia to find one cancer cell in a million.

  • 10^-5 to 10^-6 sensitivity
  • Blood-based monitoring in many settings

Flow cytometry MRD counts leukaemia cells in the bone marrow one at a time by their surface proteins, down to one in ten thousand.

  • Broadly applicable, fast (same day)
  • Works without a molecular marker
Whole-body MRIEstablished

Whole-body MRI is an MRI of the entire body without radiation, used to find spread in myeloma and to screen people with high inherited cancer risk.

  • No radiation, so repeatable
  • Bone marrow sensitivity
PET/CTStandard of care

PET and CT in one machine, so hot spots on the PET are pinned to exact locations on the CT.

  • Anatomy plus biology
  • Standard for lymphoma, lung, melanoma, head and neck staging
The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record
  • Requires a baseline sample to identify the clone
  • Persisting pre-leukaemic clones (CHIP) confound AML MRD
  • Operator and lab dependent
  • Sensitivity below molecular methods; immunophenotype shift after therapy
  • Long scan
  • Incidental findings in screening use
  • CT radiation added to PET dose
Questions to ask about this decision
  1. Between NGS-based MRD (clonoSEQ and molecular MRD), Multiparameter flow cytometry MRD, Whole-body MRI and the other options, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  4. For my situation (response assessment), which of the standard options do you recommend and why?
    Why: Guideline options include: M-protein and free light chains every cycle, MRD by sequencing or flow cytometry after transplant and during maintenance, imaging for residual focal lesions.

Add these to your appointment list, or take the full question set for this cancer.

How to read this page. Options and results come from OnCo records with their sources; the settings are the standard-of-care rows on the cancer page, and the lines of therapy are on the sequencing grid. Where a setting names one path, the choice is usually about timing, trials and where to be treated: see expert centres. OnCo is orientation, not medical advice.