Relapsed or refractory multiple myeloma

aka RRMM, Relapsed myeloma, Triple-class refractory myeloma, Penta-refractory myeloma

Myeloma almost always returns, and each return is harder to treat. Two kinds of immune therapy aimed at the BCMA protein on myeloma cells, CAR-T cells (KarMMa-3, CARTITUDE-4) and off-the-shelf bispecific antibodies (MajesTEC), now give deep remissions after other drugs fail, and a second target, GPRC5D, gives another option.

Part ofMultiple myeloma

Relapse is defined by a rising M-protein or light chains, and refractory disease by progression on or within 60 days of a treatment. Choice at each relapse depends on which classes the disease has already resisted: proteasome inhibitors, immunomodulatory drugs and CD38 antibodies define triple-class exposure, and their five main members define penta-exposure. Early relapse after a lenalidomide-based first line is usually treated with a carfilzomib or pomalidomide triplet with a CD38 antibody, or with belantamab mafodotin combinations after DREAMM-7 (belantamab-bortezomib-dexamethasone versus daratumumab-bortezomib-dexamethasone, median progression-free survival 36.6 versus 13.4 months, hazard ratio 0.41, with a survival gain) and DREAMM-8 returned the antibody-drug conjugate to the market in 2025.

BCMA-directed T-cell therapies changed the outlook for later lines. Idecabtagene vicleucel was the first CAR-T approved (2021); KarMMa-3 then showed it beat standard regimens after two to four prior lines, median progression-free survival 13.3 versus 4.4 months (hazard ratio 0.49). Ciltacabtagene autoleucel produced responses in 98 percent of heavily pretreated patients in CARTITUDE-1, with a third still progression-free at five years without further treatment, and CARTITUDE-4 showed it after one to three prior lines cut progression or death by about three quarters (hazard ratio 0.26) and lengthened life (hazard ratio 0.55), moving CAR-T to second line in 2024. Bispecific antibodies give an off-the-shelf alternative: teclistamab (MajesTEC-1, response rate 63 percent, approved 2022), elranatamab (MagnetisMM-3, 61 percent) and linvoseltamab (LINKER-MM1, 70 percent, approved 2025) against BCMA, and talquetamab (MonumenTAL-1, about 73 percent, approved 2023) against GPRC5D, which works after BCMA therapy fails. MajesTEC-3 (2025) showed teclistamab with daratumumab beating standard combinations in early relapse.

The price is toxicity and logistics: cytokine release syndrome and neurotoxicity with both approaches, delayed neurological and Parkinsonian events with cilta-cel, profound infections and hypogammaglobulinaemia with continuous BCMA bispecifics requiring immunoglobulin replacement, taste and skin toxicity with talquetamab, and manufacturing slots and hospital capacity for CAR-T. Sequencing (CAR-T before or after bispecific, BCMA then GPRC5D), fixed-duration bispecific dosing, CELMoDs such as iberdomide and mezigdomide, and trispecific antibodies are the current frontier.

State of the art

BCMA CAR-T now belongs in second line after CARTITUDE-4 lengthened life; a third of CARTITUDE-1 patients remain progression-free at five years after a single infusion.
Four approved bispecific antibodies, three against BCMA and one against GPRC5D, give off-the-shelf immune therapy with response rates of 60 to 70 percent in heavily pretreated patients.

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.

Belantamab mafodotin returned in 2025 for early relapse with a survival gain in DREAMM-7.

Red cards

From the labels and guidelines behind the standard of care. Your team's thresholds win.

Emergency services now
Blood 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.
Carfilzomib Iberdomide Mezigdomide Pomalidomide source
Emergency services now
Cytokine release syndrome
Fever of 38 C or higher, chills, low blood pressure, fast heartbeat or breathlessness, especially after a step-up dose. Boxed warning on teclistamab, epcoritamab, glofitamab, tarlatamab and blinatumomab.
Elranatamab Linvoseltamab Talquetamab Teclistamab source
Emergency services now
Cytokine release syndrome
Fever of 38 C or higher is grade 1 CRS; fever with low blood pressure, fast heartbeat, breathlessness or low oxygen is grade 2 or higher. The labels carry a boxed warning and say to report fever immediately.
Ciltacabtagene autoleucel Idecabtagene vicleucel source
Emergency services now
Skin reaction
Blisters, peeling, or sores in the mouth or eyes with a rash. Enfortumab vedotin carries a boxed warning for Stevens-Johnson syndrome and toxic epidermal necrolysis, mostly in the first cycle.
Belantamab mafodotin source
Check before combining
Pomalidomide with Dexamethasone: major interaction
Thromboembolism risk with pomalidomide-dexamethasone.. Thromboprophylaxis is standard.
Dexamethasone Pomalidomide source
Check before combining
Food and drink: Pomalidomide
Smoking induces CYP1A2 and lowers exposure by about a third.
Pomalidomide source

See all on the product pages:Belantamab mafodotin Carfilzomib Ciltacabtagene autoleucel Dexamethasone Elranatamab Iberdomide Idecabtagene vicleucel Linvoseltamab Mezigdomide Pomalidomide Talquetamab Teclistamab·Printable cards in the navigator

Anatomy and lymph node drainage

Bone marrow, lymph nodes and spleen: subsites and node stations · wireframe schematic, not to scale

Organ atlas →

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.

Subsites

Bone marrow (leukaemia, MDS, MPN, myeloma)Triple-class exposed or refractory myeloma (CAR-T, bispecifics) · Penta-refractory myeloma · Functional high-risk myeloma (relapse within 18 months of diagnosis)
Lymph node germinal centre (lymphomas)
Spleen
Blood (leukaemic phase)
Lytic bone lesions (myeloma)Extramedullary relapse
Skin and extranodal sites

Regional lymph nodes

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, Newly diagnosed multiple myeloma, transplant-ineligible, 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

Who gets it and what has changed

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.

Almost everyone with myeloma relapses eventually; with each line of treatment remissions shorten, and until 2021 patients whose disease resisted the three main drug classes survived about a year.

Group

haematologic

Cases by country

Cases by country · GLOBOCAN 2022

All countries →

No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.

Standard of care

4top

Lines of therapy by subgroup →Staging and risk scores →

Decisions you may face

3 with more than one option · full decision page →

One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.

First relapse, lenalidomide-refractory7 Triple-class exposed, two or more prior lines5 After BCMA-directed therapy4 Toxicity management

First relapse, lenalidomide-refractory

Daratumumab or isatuximab with carfilzomib or pomalidomide and dexamethasone; belantamab mafodotin with bortezomib- or pomalidomide-dexamethasone (DREAMM-7, DREAMM-8); cilta-cel after one to three lines (CARTITUDE-4).

NCCN Guidelines: Multiple Myeloma

DaratumumabIsatuximabCarfilzomibPomalidomideDexamethasoneBelantamab mafodotinDREAMM-7 DREAMM-8Ciltacabtagene autoleucelCARTITUDE-4

Triple-class exposed, two or more prior lines

BCMA CAR-T (cilta-cel or ide-cel, KarMMa-3) where slots and fitness allow; BCMA bispecific (teclistamab, elranatamab, linvoseltamab) otherwise; teclistamab-daratumumab (MajesTEC-3).

NCCN Guidelines: Multiple Myeloma

Ciltacabtagene autoleucelIdecabtagene vicleucelKarMMa-3 CARTITUDE-1TeclistamabElranatamabLinvoseltamabMajesTEC-1 MajesTEC-3 LINKER-MM1 MagnetisMM-3

After BCMA-directed therapy

Talquetamab against GPRC5D (MonumenTAL-1); selinexor combinations; CELMoDs and trispecifics in trials.

NCCN Guidelines: Multiple Myeloma

TalquetamabMonumenTAL-1SelinexorIberdomideMezigdomideBCMA-directed therapy → GPRC5D-directed therapy

Toxicity management

Step-up dosing and tocilizumab for cytokine release syndrome, immunoglobulin replacement and antimicrobial prophylaxis on bispecifics, neurological monitoring after cilta-cel, ocular examinations on belantamab.

Step-up dosing (T-cell engagers)Cytokine release syndrome (CRS)ICANS (neurotoxicity)Caution: T-cell redirectors and infections

Subtypes & biomarkers

top

Subtypes

First relapse after lenalidomide-based therapy (lenalidomide-refractory)
Early relapse, one to three prior lines (cilta-cel, CARTITUDE-4; belantamab combinations)
Triple-class exposed or refractory myeloma (CAR-T, bispecifics)
Penta-refractory myeloma
Relapse after BCMA-directed therapy (GPRC5D-directed talquetamab)
Extramedullary relapse
Functional high-risk myeloma (relapse within 18 months of diagnosis)

Biomarkers clinicians test

Classes and agents the disease is refractory to
Time from last therapy and depth of prior response
BCMA and GPRC5D expression and BCMA loss after prior BCMA therapy
Soluble BCMA
Extramedullary disease on PET-CT
Cytogenetics at relapse (del(17p), 1q gain)
Lymphocyte count and fitness for apheresis

How often this target appears

History

7top

2003Bortezomib approved for relapsed myeloma: the first proteasome inhibitor
Bortezomib
2012Carfilzomib approved; pomalidomide follows in 2013
CarfilzomibPomalidomide
2015Daratumumab, the first CD38 antibody, approved for heavily pretreated myeloma
Daratumumab
2021Ide-cel: first BCMA CAR-T approved
Idecabtagene vicleucel
2022Teclistamab: first BCMA bispecific approved (MajesTEC-1)
TeclistamabMajesTEC-1
2023KarMMa-3 and CARTITUDE-4: CAR-T beats standard regimens in randomised trials; talquetamab and elranatamab approved
KarMMa-3 CARTITUDE-4TalquetamabElranatamab
2025Linvoseltamab approved; belantamab returns after DREAMM-7 and DREAMM-8; MajesTEC-3 reads out
LinvoseltamabBelantamab mafodotinDREAMM-7 MajesTEC-3

What changed

26top

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 26 changes by month →

FollowWatch this cancer and Saved shows what changed since you last looked.Follow by feed

In development

11top

What is in development for Relapsed or refractory multiple myeloma, drawn from the whole corpus: 18 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 reported · 11

iMMagine-1 · phase 2 · 2025 · positive
CARTITUDE-1 · phase 1/2 · 2021 · positive
CARTITUDE-4 · phase 3 · 2023 · positive
DREAMM-7 · phase 3 · 2024 · positive
DREAMM-8 · phase 3 · 2024 · positive
KarMMa-3 · phase 3 · 2023 · positive
LINKER-MM1 · phase 1/2 · 2024 · positive
MagnetisMM-3 · phase 2 · 2023 · positive
MajesTEC-1 · phase 1/2 · 2022 · positive
MajesTEC-3 · phase 3 · 2025 · positive
MonumenTAL-1 · phase 1/2 · 2022 · positive

Combinations being explored · 2

BCMA-directed therapy → GPRC5D-directed therapy Caution: T-cell redirectors and infections

Ideas not yet in a trial · 1

Plan the second CAR-T target before the first one is lost

Open problems and what is being done

Sequencing CAR-T and bispecifics, and whether a second T-cell therapy works after the first.
Infections on continuous BCMA bispecifics, and whether fixed-duration dosing is safe.
CAR-T manufacturing capacity, slots and cost, and the patients who progress while waiting.

Trials

top

Trials recruiting now

Recruiting trials near you · live from ClinicalTrials.gov

Relapsed or refractory multiple myeloma

condition: Relapsed or refractory multiple myeloma

Open on ClinicalTrials.gov →

within

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

A Study to Compare the Efficacy and Safety of BMS-986393 Versus Standard Regimens in Adult Participants With Relapsed or Refractory and Lenalidomide-exposed Multiple Myeloma (QUINTESSENTIAL-2)CARTITUDE-1 CARTITUDE-4 DREAMM-7 DREAMM-8 iMMagine-1 KarMMa-3 LINKER-MM1 MagnetisMM-3 MajesTEC-1 MajesTEC-3 MonumenTAL-1

Expert centres

top

Where the expertise is

Expert centres

7 centres in 4 countries · 0 with a trial for this cancer on record · second-opinion finder →

Choose a region from the globe in the header to mark centres near you.

7 centres


Yale University Open Data Access (YODA) Project New Haven, CT · consortium	United States	none recorded	2,224	28,423	none recorded	-
Comprehensive Cancer Center Mainfranken, University Hospital Würzburg Würzburg · cancer center	Germany	none recorded	760	11,806	CAR-T cell therapy Bispecific antibodies T-cell engagers (bispecific)Radioligand therapy (beta emitters)	-
Children's Hospital of Philadelphia Philadelphia, PA · hospital	United States	none recorded	695	9,931	CAR-T cell therapy Proton therapy Germline (hereditary) testing	-
IUCT Oncopole (Institut Universitaire du Cancer de Toulouse) Toulouse · cancer center	France	none recorded	232	3,172	MRD / molecular residual disease testing CAR-T cell therapy Bispecific antibodies IMRT / IGRT (modern external beam)	-
IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola Bologna · hospital	Italy	none recorded	229	2,386	CAR-T cell therapy Bispecific antibodies Allogeneic (off-the-shelf) cell therapy	-
Society for Immunotherapy of Cancer Milwaukee, WI · consortium	United States	none recorded	6	1	Immune checkpoint inhibitors CAR-T cell therapy TIL therapy T-cell engagers (bispecific)+2	-
Winship Cancer Institute of Emory University Atlanta, GA · cancer center	United States	NCI comprehensive	not matched	-	Proton therapy Proton therapy machines: cyclotrons, synchrotrons and single-room systems	-

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 Relapsed or refractory multiple myeloma 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.

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost. The second-opinion finder explains how referral works in your country.

Questions to ask

top

Bring to your appointment

Questions to ask your oncologist about Relapsed or refractory multiple myeloma

Generated from this cancer's standard of care, biomarkers, and pipeline · 19 questions

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 Classes and agents the disease is refractory to, Time from last therapy and depth of prior response, BCMA and GPRC5D expression and BCMA loss after prior BCMA therapy, Soluble BCMA, Extramedullary disease on PET-CT), 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 First relapse after lenalidomide-based therapy, Early relapse, one to three prior lines, Triple-class exposed or refractory myeloma.
Is germline (inherited) genetic testing recommended for me or my family?
Why: Inherited variants can change treatment and matter for relatives.

First relapse, lenalidomide-refractory

For my situation (first relapse, lenalidomide-refractory), which of the standard options do you recommend and why?
Why: Guideline options include: Daratumumab or isatuximab with carfilzomib or pomalidomide and dexamethasone; belantamab mafodotin with bortezomib- or pomalidomide-dexamethasone (DREAMM-7, DREAMM-8); cilta-cel after one to three lines (CARTITUDE-4).
Am I a candidate for Daratumumab, Isatuximab, Carfilzomib 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 DREAMM-7 and DREAMM-8 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Triple-class exposed, two or more prior lines

For my situation (triple-class exposed, two or more prior lines), which of the standard options do you recommend and why?
Why: Guideline options include: BCMA CAR-T (cilta-cel or ide-cel, KarMMa-3) where slots and fitness allow; BCMA bispecific (teclistamab, elranatamab, linvoseltamab) otherwise; teclistamab-daratumumab (MajesTEC-3).
Am I a candidate for Ciltacabtagene autoleucel, Idecabtagene vicleucel, Teclistamab 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 KarMMa-3 and CARTITUDE-1 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

After BCMA-directed therapy

For my situation (after bcma-directed therapy), which of the standard options do you recommend and why?
Why: Guideline options include: Talquetamab against GPRC5D (MonumenTAL-1); selinexor combinations; CELMoDs and trispecifics in trials.
Am I a candidate for Talquetamab, Selinexor, Iberdomide 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 MonumenTAL-1 apply to someone like me?
Why: Trial populations differ from individual patients; ask how closely you match.

Toxicity management

For my situation (toxicity management), which of the standard options do you recommend and why?
Why: Guideline options include: Step-up dosing and tocilizumab for cytokine release syndrome, immunoglobulin replacement and antimicrobial prophylaxis on bispecifics, neurological monitoring after cilta-cel, ocular examinations on belantamab.

Any stage

Are there clinical trials I could join, for example of Ciltacabtagene autoleucel, Teclistamab, Talquetamab, Linvoseltamab?
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 “Sequencing CAR-T and bispecifics, and whether a second T-cell therapy works after the first”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.
I read that “Infections on continuous BCMA bispecifics, and whether fixed-duration dosing is safe”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.