Newly diagnosed multiple myeloma, transplant-ineligible
Most people with newly diagnosed myeloma are too old or frail for a stem cell transplant. Combining a CD38 antibody with lenalidomide and dexamethasone (MAIA) and, for the fitter, with bortezomib as well (IMROZ), now keeps the disease away for around five years in many and lengthens life.
Overview
Transplant ineligibility is decided on frailty, comorbidity and organ function using the IMWG frailty index rather than age alone, and treatment intensity is scaled to it: fit older patients receive quadruplets, frail patients doublets or attenuated triplets with dose reductions. Continuous therapy until progression is the rule, since SWOG S0777 and FIRST showed that stopping shortens remission. Supportive care carries as much weight as the anti-myeloma drugs: bone protection with zoledronic acid or denosumab, infection prophylaxis, thrombosis prophylaxis on lenalidomide and attention to neuropathy from bortezomib.
MAIA (2019) randomised 737 patients, median age 73, to daratumumab-lenalidomide-dexamethasone or lenalidomide-dexamethasone until progression: progression or death fell by 44 percent (hazard ratio 0.56), median progression-free survival later reached about five years, and the antibody lengthened overall survival (hazard ratio 0.68 at five years), making daratumumab-Rd the standard for older patients. IMROZ (2024) tested a quadruplet in fitter transplant-ineligible patients up to 80: isatuximab with bortezomib-lenalidomide-dexamethasone against VRd gave five-year progression-free survival of 63.2 percent versus 45.2 percent (hazard ratio 0.60), and CEPHEUS did the same with daratumumab-VRd, raising MRD negativity from 39.4 to 60.9 percent (progression-free survival hazard ratio 0.57). Both quadruplets are approved.
The frail remain under-served: they were largely excluded from these trials, tolerate bortezomib poorly, and gain less from a fourth drug. The BENEFIT trial suggested that weekly bortezomib added to isatuximab-Rd improves MRD negativity in this group, and dose-attenuated regimens, fixed-duration therapy, and bispecific antibodies in the front line (MajesTEC-7, CEPHEUS-type designs) are the current trials.
State of the art
- A CD38 antibody with lenalidomide-dexamethasone (MAIA) is standard for older patients and lengthens life; the fitter now receive quadruplets after IMROZ and CEPHEUS.
- Frailty assessment, not age, sets treatment intensity.
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- Median progression-free survival in trial populations has reached about five years without a transplant.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBlood clot (lenalidomide, pomalidomide, thalidomide)
A swollen painful calf, or sudden breathlessness with chest pain; venous and arterial thromboembolism is a boxed warning and blood-thinning prophylaxis is recommended.
- Check before combiningLenalidomide with Dexamethasone: major interaction
Venous and arterial thromboembolism risk rises markedly with lenalidomide plus dexamethasone (and further with erythropoietin or oestrogens).. Thromboprophylaxis (aspirin, LMWH or a DOAC by risk) is standard.
- Check before combiningKidneys: Lenalidomide
Dose by creatinine clearance: 10 mg daily for CrCl 30-60, 15 mg every other day below 30, 5 mg daily on dialysis.
- Check before combiningLiver: Bortezomib
Start at 0.7 mg/m² in moderate or severe impairment.
- Good to knowInfusion reactions, hypersensitivity and extravasation
Reactions around the moment a drug is given: chills, fever or breathlessness from antibodies (infusion reactions), true allergy (hypersensitivity, rarely anaphylaxis), and leakage of a damaging drug into tissue around the vein (extravasation).
- Good to knowPeripheral neuropathy (chemotherapy-induced)
Nerve damage from chemotherapy that causes numbness, tingling and pain in the hands and feet, and sometimes weakness or hearing loss. It builds up with each dose, can be permanent, and is the main reason oxaliplatin, taxanes and vincristine have to be stopped or reduced.
See all on the product pages:BortezomibDaratumumabDexamethasoneLenalidomide·Printable cards in the navigator
Anatomy and lymph node drainage
- Bone marrow (leukaemia, MDS, MPN, myeloma)
- Lymph node germinal centre (lymphomas)
- Spleen
- Blood (leukaemic phase)
- Lytic bone lesions (myeloma)
- Skin and extranodal sites
- Nodes: cervical
- Nodes: axillary
- Nodes: mediastinal
- Nodes: para-aortic and mesenteric
- Nodes: inguinal
Leukaemias, myeloma and MDS live in the marrow and blood; lymphomas grow in lymph nodes and spleen. The node stations are the disease map, not a route of spread, and staging counts them.
- Bone marrow (leukaemia, MDS, MPN, myeloma)Fit transplant-ineligible myeloma (quadruplet candidates, up to about 80) · Intermediate-fitness myeloma (daratumumab-Rd) · Frail myeloma (attenuated doublets or triplets, dose-reduced) · High-risk cytogenetic myeloma in older patients · Myeloma with renal failure at diagnosis
- Lymph node germinal centre (lymphomas)
- Spleen
- Blood (leukaemic phase)
- Lytic bone lesions (myeloma)
- Skin and extranodal sites
- cervical
- axillary
- mediastinal
- para-aortic and mesenteric
- inguinal
In lymphoma the node stations are the disease itself; staging (Ann Arbor / Lugano) counts how many regions and sides of the diaphragm are involved.
Same organ: Marginal zone lymphoma, Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome), Primary mediastinal (thymic) large B-cell lymphoma, Leukaemia (all types), Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Chronic lymphocytic leukaemia, Chronic myeloid leukaemia (CML), Diffuse large B-cell lymphoma, Follicular lymphoma, Hodgkin lymphoma, Mantle cell lymphoma, Multiple myeloma, Non-Hodgkin lymphoma (all types), Myelodysplastic syndromes / neoplasms (MDS), Myeloproliferative neoplasms (PV, ET, myelofibrosis), Polycythaemia vera (PV), Essential thrombocythaemia (ET), Waldenström macroglobulinaemia, Hairy cell leukaemia, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Burkitt lymphoma, HIV-associated (AIDS-related) lymphomas, Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Systemic mastocytosis, Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, Langerhans cell histiocytosis (LCH), Post-transplant lymphoproliferative disorder (PTLD), FLT3-mutated acute myeloid leukaemia, IDH1- and IDH2-mutated acute myeloid leukaemia, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Secondary and therapy-related acute myeloid leukaemia, Acute promyelocytic leukaemia, Acute myeloid leukaemia in older or unfit patients, Smouldering multiple myeloma, Newly diagnosed multiple myeloma, transplant-eligible, Relapsed or refractory multiple myeloma, Plasma cell leukaemia, Lower-risk myelodysplastic syndromes, Higher-risk myelodysplastic syndromes, Chronic lymphocytic leukaemia, first treatment, Relapsed or refractory chronic lymphocytic leukaemia, Richter transformation of chronic lymphocytic leukaemia, Chronic myeloid leukaemia, chronic phase, Chronic myeloid leukaemia, accelerated and blast phase, Primary myelofibrosis
More than half of people diagnosed with myeloma, typically over 70 or with frailty or organ disease, are not candidates for high-dose chemotherapy; their outlook has improved more than any other group's in the past decade.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Isatuximab or daratumumab with bortezomib, lenalidomide and dexamethasone (IMROZ, CEPHEUS), continuing the antibody and lenalidomide until progression.
Daratumumab with lenalidomide and dexamethasone until progression (MAIA).
Daratumumab-Rd with reduced lenalidomide and dexamethasone, or lenalidomide-dexamethasone alone, with early dose reduction and steroid tapering.
Bisphosphonate or denosumab bone protection, antiviral and thrombosis prophylaxis, vaccination, renal protection and early management of neuropathy.
Subtypes & biomarkers
top- Fit transplant-ineligible myeloma (quadruplet candidates, up to about 80)
- Intermediate-fitness myeloma (daratumumab-Rd)
- Frail myeloma (attenuated doublets or triplets, dose-reduced)
- High-risk cytogenetic myeloma in older patients
- Myeloma with renal failure at diagnosis
- IMWG frailty index
- R-ISS and R2-ISS stage
- FISH cytogenetics : del(17p), t(4;14), t(14;16), gain 1q
- Renal function and light chain burden
- MRD by sequencing or flow cytometry
- Peripheral neuropathy baseline
How often this target appears
- 1969Melphalan and prednisone become the first standard for myeloma
- 2006Thalidomide with melphalan-prednisone improves survival in older patients
- 2014FIRST: continuous lenalidomide-dexamethasone beats melphalan-prednisone-thalidomide
- 2017SWOG S0777: bortezomib added to Rd lengthens life without transplant
- 2019MAIA: daratumumab-Rd approved for transplant-ineligible myeloma
- 2024IMROZ and CEPHEUS: quadruplets for fit transplant-ineligible patients
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 9 changes by month →- 2026-09-17This recordNewly diagnosed multiple myeloma, transplant-ineligibleFacts on this page last checked
When this page itself was last checked or edited.
- 2024Trial resultCEPHEUSCEPHEUS reported
MRD-neg 60.
- 2024Trial resultIMROZIMROZ reported
PFS HR 0.
- 2024MilestoneIMROZIMROZ and CEPHEUS: quadruplets for fit transplant-ineligible patients
A milestone in how this cancer is treated.
- 2019MilestoneDaratumumabMAIA: daratumumab-Rd approved for transplant-ineligible myeloma
A milestone in how this cancer is treated.
- 2017MilestoneBortezomibSWOG S0777: bortezomib added to Rd lengthens life without transplant
A milestone in how this cancer is treated.
What is in development for Newly diagnosed multiple myeloma, transplant-ineligible, drawn from the whole corpus: 3 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Trials under way · 1
- CARTITUDE-5 · phase 3 · Janssen
Trials reported · 2
Open problems and what is being done
Frail patients were excluded from the quadruplet trials and gain least from them.
Whether treatment can be fixed in duration or MRD-guided rather than continued until progression.
and how the field plans to fix it →What is being done about thisRecurrence and residual diseaseAvailable now- NGS-based MRD (clonoSEQ and molecular MRD)Standard of care
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Background: MRD negativity (myeloma, 10⁻⁵ / 10⁻⁶). Also on OnCo: Treatment journeys · Survivorship planner.
The cost of continuous antibody therapy for years in the largest myeloma population.
and how the field plans to fix it →What is being done about thisCost and accessAvailable nowIn trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Financial help · Coverage by country · HTA decisions.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
New Haven, CT · consortium | United States | none recorded | 0 | 2,224 | 28,423 | none recorded | - |
Rochester, NY · cancer center | United States | 0 | 861 | 12,212 | - | ||
Würzburg · cancer center | Germany | none recorded | 0 | 760 | 11,806 | - | |
Leuven · cancer center | Belgium | none recorded | 0 | 343 | 5,732 | - | |
Toulouse · cancer center | France | none recorded | 0 | 232 | 3,172 | - | |
| Italy | none recorded | 0 | 229 | 2,386 | - | ||
Luxembourg · consortium | Luxembourg | none recorded | 0 | not matched | - | - | |
Aurora, ON · consortium | Canada | none recorded | 0 | not matched | - | - | |
Jerusalem · hospital | Israel | none recorded | 0 | not matched | - | - | |
Atlanta, GA · cancer center | United States | 0 | not matched | - | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Newly diagnosed multiple myeloma, transplant-ineligible but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Newly diagnosed multiple myeloma, transplant-ineligible
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example IMWG frailty index, R-ISS and R2-ISS stage, FISH cytogenetics: del, t, t, gain 1q, Renal function and light chain burden, MRD by sequencing or flow cytometry), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Fit transplant-ineligible myeloma, Intermediate-fitness myeloma, Frail myeloma.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Fit, transplant-ineligible
- For my situation (fit, transplant-ineligible), which of the standard options do you recommend and why?Why: Guideline options include: Isatuximab or daratumumab with bortezomib, lenalidomide and dexamethasone (IMROZ, CEPHEUS), continuing the antibody and lenalidomide until progression.
- Am I a candidate for Isatuximab, Daratumumab, Bortezomib or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of IMROZ and CEPHEUS apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Intermediate fitness
- For my situation (intermediate fitness), which of the standard options do you recommend and why?Why: Guideline options include: Daratumumab with lenalidomide and dexamethasone until progression (MAIA).
- Am I a candidate for Daratumumab, Lenalidomide, Dexamethasone, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Frail
- For my situation (frail), which of the standard options do you recommend and why?Why: Guideline options include: Daratumumab-Rd with reduced lenalidomide and dexamethasone, or lenalidomide-dexamethasone alone, with early dose reduction and steroid tapering.
- Am I a candidate for Daratumumab, Lenalidomide, Dexamethasone, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Supportive care, all patients
- For my situation (supportive care, all patients), which of the standard options do you recommend and why?Why: Guideline options include: Bisphosphonate or denosumab bone protection, antiviral and thrombosis prophylaxis, vaccination, renal protection and early management of neuropathy.
Any stage
- Are there clinical trials I could join, for example of Isatuximab, Daratumumab, Teclistamab, CARTITUDE-5?Why: 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?Why: 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?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Frail patients were excluded from the quadruplet trials and gain least from them”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Whether treatment can be fixed in duration or MRD-guided rather than continued until progression”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Newly diagnosed multiple myeloma, transplant-ineligible, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
13targets
5drugs
9companies
7terms
6trials
3key papers
2CEPHEUS extends the quadruplet standard to patients who are not going to transplant, closing the gap between transplant-eligible and ineligible populations. It is also one of the first phase 3 trials to be designed around MRD-negativity as the primary endpoint, which could shorten future myeloma trials by years. Frailer patients still need dose-adapted approaches.
MAIA made a daratumumab-based triplet the standard first treatment for older or frail myeloma patients, replacing Rd alone. It proved an anti-CD38 antibody could improve survival, not just delay progression, when used up front. Quadruplets built on this backbone are now being tested in the same population.
Latest papers
topQuery for this cancer: (TITLE:"Newly diagnosed multiple myeloma, transplant-ineligible" OR ABSTRACT:"Newly diagnosed multiple myeloma, transplant-ineligible" OR TITLE:"Transplant-ineligible myeloma" OR ABSTRACT:"Transplant-ineligible myeloma" OR TITLE:"TI NDMM" OR ABSTRACT:"TI NDMM" OR TITLE:"Myeloma in older or frail patients" OR ABSTRACT:"Myeloma in older or frail patients" OR TITLE:"Newly diagnosed myeloma not for transplant" OR ABSTRACT:"Newly diagnosed myeloma not for transplant") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Newly diagnosed multiple myeloma, transplant-ineligible, not a curated reading list.
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