# Newly diagnosed multiple myeloma, transplant-ineligible

Source: https://onco.cc/cancers/myeloma-transplant-ineligible/  
OnCo record `myeloma-transplant-ineligible` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: Transplant-ineligible myeloma; TI NDMM; Myeloma in older or frail patients; Newly diagnosed myeloma not for transplant
- Tags: subtype-page
- Group: haematologic
- Burden: 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.
- Subtypes: 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
- Biomarkers: 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

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/myeloma-transplant-ineligible/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/myeloma-transplant-ineligible/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/myeloma-transplant-ineligible/#what-it-is [5 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/myeloma-transplant-ineligible/#finding-it [6 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/myeloma-transplant-ineligible/#treating-it [4 settings, 3 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/myeloma-transplant-ineligible/#evidence [9 trials, 2 key papers, 6 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/myeloma-transplant-ineligible/#science [7 targets]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/myeloma-transplant-ineligible/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/myeloma-transplant-ineligible/#living-with-it [17 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/myeloma-transplant-ineligible/coming/ [9 medicines, 8 trials, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/myeloma-transplant-ineligible/data/ [55 connected records]

## Standard of care

- Fit, transplant-ineligible: Isatuximab or daratumumab with bortezomib, lenalidomide and dexamethasone (IMROZ, CEPHEUS), continuing the antibody and lenalidomide until progression. ([Isatuximab](https://onco.cc/drugs/isatuximab/), [Daratumumab](https://onco.cc/drugs/daratumumab/), [Bortezomib](https://onco.cc/drugs/bortezomib/), [Lenalidomide](https://onco.cc/drugs/lenalidomide/), [Dexamethasone](https://onco.cc/drugs/dexamethasone/), [IMROZ](https://onco.cc/trials/imroz/), [CEPHEUS](https://onco.cc/trials/cepheus/), [VRd and Dara-VRd (myeloma induction regimens)](https://onco.cc/terms/vrd/))
- Intermediate fitness: Daratumumab with lenalidomide and dexamethasone until progression (MAIA). ([Daratumumab](https://onco.cc/drugs/daratumumab/), [Lenalidomide](https://onco.cc/drugs/lenalidomide/), [Dexamethasone](https://onco.cc/drugs/dexamethasone/))
- Frail: Daratumumab-Rd with reduced lenalidomide and dexamethasone, or lenalidomide-dexamethasone alone, with early dose reduction and steroid tapering. ([Daratumumab](https://onco.cc/drugs/daratumumab/), [Lenalidomide](https://onco.cc/drugs/lenalidomide/), [Dexamethasone](https://onco.cc/drugs/dexamethasone/), [Geriatric assessment](https://onco.cc/technologies/geriatric-assessment/))
- Supportive care, all patients: Bisphosphonate or denosumab bone protection, antiviral and thrombosis prophylaxis, vaccination, renal protection and early management of neuropathy. ([Transfusion support and anaemia management](https://onco.cc/technologies/transfusion-support/), [Maintenance therapy](https://onco.cc/terms/maintenance-therapy/))

## 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.
- Median progression-free survival in trial populations has reached about five years without a transplant.

## Open problems

- 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.
- The cost of continuous antibody therapy for years in the largest myeloma population.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Multiple_myeloma
- Wikipedia: https://en.wikipedia.org/wiki/Multiple_myeloma
- NCCN Guidelines: Multiple Myeloma: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1445

## Connected records

- cancers: [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/), [Newly diagnosed multiple myeloma, transplant-eligible](https://onco.cc/cancers/myeloma-transplant-eligible/), [Plasma cell leukaemia](https://onco.cc/cancers/plasma-cell-leukaemia/), [Relapsed or refractory multiple myeloma](https://onco.cc/cancers/myeloma-relapsed-refractory/), [Smouldering multiple myeloma](https://onco.cc/cancers/smouldering-myeloma/)
- technologies: [Geriatric assessment](https://onco.cc/technologies/geriatric-assessment/), [NGS-based MRD (clonoSEQ and molecular MRD)](https://onco.cc/technologies/ngs-mrd-clonoseq/), [Transfusion support and anaemia management](https://onco.cc/technologies/transfusion-support/)
- targets: [CD38](https://onco.cc/targets/cd38/), [Cereblon (CRBN)](https://onco.cc/targets/cereblon/), [Proteasome (PSMB5)](https://onco.cc/targets/proteasome/)
- terms: [Immunomodulatory drugs (IMiDs) and CELMoDs](https://onco.cc/terms/imid/), [M-protein, immunofixation and serum free light chains](https://onco.cc/terms/m-protein-free-light-chains/), [Maintenance therapy](https://onco.cc/terms/maintenance-therapy/), [MRD negativity (myeloma, 10⁻⁵ / 10⁻⁶)](https://onco.cc/terms/mrd-negativity-myeloma/), [Proteasome inhibitor (bortezomib, carfilzomib, ixazomib)](https://onco.cc/terms/proteasome-inhibitor/), [R-ISS / R2-ISS staging](https://onco.cc/terms/r-iss/), [VRd and Dara-VRd (myeloma induction regimens)](https://onco.cc/terms/vrd/)
- trials: [A Study of Belantamab Mafodotin Administered in Combination With Lenalidomide and Dexamethasone (BRd) Versus Daratumumab, Lenalidomide, and Dexamethas](https://onco.cc/trials/nct06679101/), [A Study of Teclistamab in Combination With Daratumumab and Lenalidomide (Tec-DR) and Talquetamab in Combination With Daratumumab and Lenalidomide (Tal](https://onco.cc/trials/nct05552222/), [A Study to Assess A Change in Disease Activity and Adverse Events of Intravenous Etentamig and Daratumumab (Etentamig+D) Compared to Daratumumab, Lena](https://onco.cc/trials/nct07095452/), [A Study to Evaluate the Safety and Efficacy of SCTC21C in Combination With Bortezomib, Lenalidomide and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Not Eligible for Transplant](https://onco.cc/trials/nct07297329/), [A Study to Learn About the Effects of the Combination of Elranatamab, Daratumumab and Lenalidomide Compared With Daratumumab, Bortezomib, Lenalidomide](https://onco.cc/trials/nct05623020/), [CARTITUDE-5](https://onco.cc/trials/cartitude-5/), [CEPHEUS](https://onco.cc/trials/cepheus/), [IMROZ](https://onco.cc/trials/imroz/), [MAIA](https://onco.cc/trials/maia/)
- key papers: [CEPHEUS: daratumumab quadruplet for newly diagnosed myeloma patients not having a transplant, with MRD-negativity as the main endpoint](https://onco.cc/key-papers/paper-cepheus-dara-vrd-natmed-2025/), [MAIA: adding daratumumab to lenalidomide-dexamethasone for older patients with newly diagnosed myeloma who cannot have a transplant](https://onco.cc/key-papers/paper-maia-daratumumab-rd-nejm-2019/)
- drugs: [Bortezomib](https://onco.cc/drugs/bortezomib/), [Daratumumab](https://onco.cc/drugs/daratumumab/), [Dexamethasone](https://onco.cc/drugs/dexamethasone/), [Isatuximab](https://onco.cc/drugs/isatuximab/), [Lenalidomide](https://onco.cc/drugs/lenalidomide/), [Melphalan (including hepatic delivery system)](https://onco.cc/drugs/melphalan/), [Prednisone](https://onco.cc/drugs/prednisone/), [Teclistamab](https://onco.cc/drugs/teclistamab/), [Thalidomide](https://onco.cc/drugs/thalidomide/)
- biomarkers: [CD38 expression](https://onco.cc/biomarkers/cd38-expression/)

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JSON: https://onco.cc/api/v1/entities/myeloma-transplant-ineligible.json