Key points
- Multiple myeloma is a cancer of the plasma cells in the bone marrow, and it almost always starts from a symptom-free precursor stage called MGUS [1, 2].
- Diagnosis is based on the International Myeloma Working Group (IMWG) criteria and the presence of CRAB organ damage or SLiM high-risk biomarkers [1].
- Induction with the three-drug regimen VRd (bortezomib, lenalidomide and dexamethasone), autologous stem cell transplantation and lenalidomide maintenance are the backbone of treatment for transplant-eligible patients [14, 15]; adding daratumumab (the four-drug regimen D-VRd) raised four-year progression-free survival to 84.3% in the PERSEUS trial, and D-VRd is the new standard of care in the EHA-EMN guideline (2025) [3, 19].
- In relapsed disease, three-drug regimens based on carfilzomib or pomalidomide and daratumumab-containing combinations are the mainstay of treatment [19, 21, 22], and in later lines, CAR T-cell therapy (ide-cel and cilta-cel) and bispecific antibodies (teclistamab, elranatamab, talquetamab) produce deep responses [4, 5, 6, 7, 8].
- Supportive care, especially protecting bone health and preventing infection, is an integral part of treatment [9, 10].
What is multiple myeloma?
Plasma cells are a type of white blood cell in the bone marrow that make antibodies. In multiple myeloma, a single clone of plasma cells multiplies out of control and produces large amounts of one identical or incomplete antibody, called monoclonal protein (M protein), or of free light chains. These cells can destroy bone, impair kidney function, reduce normal blood cell production and weaken the immune system [1].
Myeloma is one of the three main groups of blood cancers; for an overview, see the blood cancers page.
| Condition | Main criteria (IMWG) | Course and management |
|---|---|---|
| MGUS (monoclonal gammopathy of undetermined significance) | Serum M protein below 3 g/dL, bone marrow plasma cells below 10%, no organ damage [1] | Low risk of progression; periodic follow-up only [2] |
| Smoldering myeloma | Serum M protein 3 g/dL or more (or urinary M protein 500 mg per 24 hours or more) and/or plasma cells 10–60%, no organ damage [1] | Higher risk of progression than MGUS [11]; in high-risk cases, early treatment is considered [12, 23] |
| Multiple myeloma | Plasma cells 10% or more (or biopsy-proven plasmacytoma) plus at least one myeloma-defining event (CRAB or SLiM) [1] | Requires treatment |
Signs and symptoms
The symptoms of myeloma are often summarized by the acronym CRAB [1]:
- C – high calcium: thirst, frequent urination, constipation, fatigue and confusion
- R – renal (kidney) failure: caused by light chains depositing in the kidneys
- A – anemia: fatigue and shortness of breath
- B – bone lesions: bone pain (especially in the back and ribs) and fractures from minor injuries
Repeated infections (such as pneumonia) are also common because the production of normal antibodies falls, and infection remains a leading cause of complications and death in these patients [10].
Warning signs
Go to the emergency department right away in these situations:
- Sudden weakness or numbness in your legs, or loss of bladder or bowel control together with back pain: this can be a sign of pressure on the spinal cord and needs urgent treatment (radiotherapy or surgery) [9].
- Confusion, severe drowsiness and extreme thirst: these may be signs of a very high calcium level.
Diagnosis and staging
Diagnostic tests for myeloma
- 1
Serum and urine protein electrophoresis and immunofixation (SPEP/UPEP)
To detect and measure M protein and determine its type (such as IgG or IgA) [19].
- 2
Serum free light chains (FLC)
Measures kappa and lambda chains and their ratio; a very high ratio is itself one of the diagnostic criteria for myeloma [1].
- 3
Bone marrow aspiration and biopsy
Determines the percentage of clonal plasma cells and allows genetic testing (FISH) for high-risk genetic changes, which are used to assess risk and prognosis [13].
- 4
- 5
General tests
Blood count, calcium, creatinine, albumin, beta-2 microglobulin and LDH, which are used together with genetic findings in international staging (R-ISS and R2-ISS) [19].
For physicians
| Criterion | Definition |
|---|---|
| C – Hypercalcemia | Serum calcium more than 0.25 mmol/L (more than 1 mg/dL) above the upper limit of normal or more than 2.75 mmol/L (more than 11 mg/dL) [1] |
| R – Renal insufficiency | Creatinine clearance less than 40 mL/min or serum creatinine more than 2 mg/dL [1] |
| A – Anemia | Hemoglobin less than 10 g/dL or more than 2 g/dL below the lower limit of normal [1] |
| B – Bone lesions | One or more lytic lesions on radiography, CT or PET-CT [1] |
| S – Sixty percent | Clonal bone marrow plasma cells 60% or more [1] |
| Li – Light chains | Involved:uninvolved free light chain ratio 100 or more (with an involved light chain level of at least 100 mg/L) [1] |
| M – MRI | More than one focal lesion (5 mm or larger) on MRI [1, 19] |
MGUS and smoldering myeloma
MGUS is a common, symptom-free condition that is often found by chance on a blood test. In a long-term Mayo Clinic study of 1,384 patients, the cumulative probability of progression to myeloma or a related disorder was 12% at 10 years, 25% at 20 years and 30% at 25 years [2].
Smoldering myeloma carries a higher risk: the risk of progression was 10% per year for the first five years, about 3% per year over the next five years and 1% per year after that [11]. Regular monitoring remains the standard approach for most patients [19]. For patients with high-risk smoldering myeloma, early treatment with oral lenalidomide [23] or subcutaneous daratumumab [12] has reduced the risk of progression in trials, and daratumumab also improved overall survival in the AQUILA trial [12]. The EHA-EMN guideline (2025) regards three years of daratumumab treatment as an option that can be considered in high-risk smoldering myeloma [19].
Most people with MGUS never develop myeloma [2]. Even so, regular follow-up with blood tests helps detect any change early.
Treatment of newly diagnosed myeloma
Treatment pathway for transplant-eligible patients
- 1
Induction therapy: VRd or the four-drug regimen D-VRd
Treatment starts with several cycles of a drug combination. The three-drug regimen VRd, made up of bortezomib, lenalidomide and dexamethasone, is the backbone of induction therapy and was used together with transplantation in the IFM 2009 trial [14]. Adding the anti-CD38 antibody daratumumab (the four-drug regimen D-VRd) markedly prolonged disease control in the PERSEUS trial, and in most patients, residual disease could not be detected even with highly sensitive tests (MRD) [3]. The EHA-EMN guideline (2025) regards the four-drug regimens D-VRd and Isa-VRd as the new standard for induction and also lists VRd as an option that can be used [19].
- 2
Stem cell collection and autologous transplantation
After high-dose chemotherapy with melphalan, the patient's own stem cells are given back. In the IFM 2009 trial, transplantation prolonged disease control, although four-year overall survival did not differ [14].
- 3
Consolidation therapy
Short courses of the same induction regimen after transplantation, which were part of the treatment plan in PERSEUS [3].
- 4
Maintenance therapy
Oral lenalidomide is continued for a long period. In a meta-analysis of trials, lenalidomide maintenance more than doubled the duration of disease control and reduced the risk of death, although the risk of second cancers was slightly higher [15]. In PERSEUS, daratumumab was also added to maintenance, and the EHA-EMN guideline regards the combination of daratumumab and lenalidomide as the new standard for maintenance [3, 19].
Transplant-ineligible patients
In older patients or those with other health conditions, regimens without transplantation are also highly effective. In the SWOG S0777 trial, in patients without plans for immediate transplantation, the three-drug regimen VRd improved both disease control and overall survival compared with lenalidomide and dexamethasone (Rd) [20]. Adding an anti-CD38 antibody has improved results even further: in the MAIA trial, adding daratumumab to lenalidomide and dexamethasone (DRd) nearly doubled the duration of disease control and increased overall survival [16]; the four-drug regimens D-VRd (CEPHEUS trial) [24] and Isa-VRd with isatuximab (IMROZ trial) [17] also reduced the risk of disease progression or death compared with VRd. The EHA-EMN guideline (2025) recommends D-VRd or Isa-VRd for patients under 80 years of age without significant frailty, regards DRd as a valuable option especially for frailer patients, and also lists VRd as an option that can be used; the choice of regimen should be based on biological age and degree of frailty [19].
Treatment of relapsed myeloma, CAR T-cell therapy and bispecific antibodies
Myeloma usually relapses after a period of remission, and patients receive several lines of treatment over time. In early relapses, three-drug regimens that include drugs to which the disease has not become resistant are the mainstay of treatment [19]; for example, adding carfilzomib to lenalidomide and dexamethasone (KRd) [21] and the regimen of pomalidomide, bortezomib and dexamethasone (PVd) in patients previously treated with lenalidomide [22] prolonged disease control. At first relapse, the EHA-EMN guideline (2025) prefers anti-CD38-containing three-drug combinations (such as daratumumab with lenalidomide and dexamethasone, or with carfilzomib and dexamethasone) and also regards KRd and PVd as valid options [19].
In later lines or refractory disease, two new targets on myeloma cells, BCMA and GPRC5D, have made highly effective immunotherapies possible.
New immunotherapies in relapsed myeloma
Idecabtagene vicleucel (ide-cel)
A BCMA-directed CAR T-cell therapy given as a single infusion. In the KarMMa-3 trial, in patients who had previously received the three main drug classes, disease control lasted markedly longer than with standard regimens [26].
Ciltacabtagene autoleucel (cilta-cel)
Teclistamab
A BCMA×CD3 bispecific antibody, given as an injection under the skin, that links the body's T cells to myeloma cells. In the MajesTEC-1 trial, in patients who had already received several lines of treatment, more than half of patients responded [6].
Elranatamab
A BCMA×CD3 bispecific antibody given as an injection under the skin. In the MagnetisMM-3 trial, in patients who had not previously received BCMA-directed therapy, more than half of patients responded [7].
Talquetamab
The first bispecific antibody against GPRC5D, a target different from BCMA, which produced responses in most patients; skin and nail side effects and changes in taste are characteristic of this drug [8].
Supportive care
Main pillars of supportive care
Bone-protecting drugs
The International Myeloma Working Group regards zoledronic acid as the preferred drug for all newly diagnosed patients, with or without bone lesions; denosumab is a suitable option, especially in patients with kidney failure [9, 19]. In a large trial, denosumab was as effective as zoledronic acid in preventing bone complications and caused less kidney damage, but low blood calcium was more common with it [18].
Pain and fractures
Injecting bone cement into fractured vertebrae (vertebroplasty/kyphoplasty) is effective for painful fractures; radiotherapy is used for uncontrolled pain or pressure on the spinal cord, and surgery for fractures of the long bones or an unstable spine [9].
Infection prevention
Vaccination, preventive antimicrobial medicines, following infection-control measures and, in some patients, intravenous immunoglobulin replacement are the cornerstones of infection prevention [10]. This is especially important during treatment with bispecific antibodies [6, 7].
What should I do after diagnosis?
Frequently asked questions
Can multiple myeloma be cured?
Do all patients need a bone marrow transplant?
Should smoldering myeloma be treated?
What is the difference between CAR T-cell therapy and a bispecific antibody?
CAR T cells are made once, from the patient's own cells; a bispecific antibody is a ready-to-use drug that is given as regular, ongoing injections and links the body's T cells to myeloma cells. Both can cause cytokine release syndrome, and bispecifics carry a high risk of infection [4, 6].
Why does back pain matter in myeloma?
Myeloma can cause compression fractures of the vertebrae. New or severe back pain should be checked, and back pain together with leg weakness is an emergency [9].
Recent evidence and advances (for physicians)
For physicians
Diagnosis and risk assessment
- Definition of high-risk myeloma: the IMS/IMWG consensus (2025) defines high-risk myeloma by any of the following findings: del(17p) with a clonal fraction above 20% or a TP53 mutation; translocation t(4;14), t(14;16) or t(14;20) together with 1q+ or del(1p32); biallelic del(1p32), or monoallelic deletion together with 1q+; and beta-2 microglobulin 5.5 mg/L or higher with normal creatinine [13].
- Staging and prognostic factors: the EHA-EMN guideline (2025) has incorporated R2-ISS staging and newer prognostic factors (MRD, circulating plasma cells and mass spectrometry-based measurement of monoclonal protein) into its recommendations [19].
High-risk smoldering myeloma
- E3A06: in intermediate- or high-risk patients, single-agent lenalidomide compared with observation increased 3-year PFS from 66% to 91% (HR 0.28) [23].
- AQUILA: subcutaneous daratumumab compared with active monitoring reduced the risk of progression or death by 51% and provided the first randomized OS data for early intervention [12].
Newly diagnosed myeloma
- Autologous stem cell transplantation (IFM 2009): transplantation after VRd increased median PFS from 36 to 50 months, with no difference in 4-year OS (81% vs 82%) [14].
- Quadruplet induction in transplant-eligible patients (PERSEUS): compared with VRd, D-VRd achieved a 48-month PFS of 84.3% vs 67.7% (HR for progression or death 0.42), and the MRD-negativity rate was 75.2% vs 47.5% [3].
- Lenalidomide maintenance (meta-analysis): median PFS 52.8 vs 23.5 months and HR for death 0.75, with a slightly higher risk of second primary malignancies [15].
- Transplant-ineligible patients: in SWOG S0777 (patients without intent for immediate transplantation), VRd compared with Rd increased median PFS from 30 to 43 months [20]. In MAIA, with more than five years of follow-up, DRd increased median PFS from 34.4 to 61.9 months, and 5-year OS was 66.6% vs 53.6% (HR 0.66) [16]. In CEPHEUS, D-VRd compared with VRd increased the MRD-negativity rate from 39.4% to 60.9% and reduced the risk of progression or death by 43% [24]. In IMROZ, Isa-VRd achieved a 60-month PFS of 63.2% vs 45.2% with VRd [17].
Relapsed myeloma
- Triplet regimens: KRd (ASPIRE) [21] and PVd in lenalidomide-pretreated patients (OPTIMISMM; median PFS 11.2 vs 7.1 months with bortezomib and dexamethasone; HR 0.61) are proven triplet regimens [22].
- CAR-T in earlier lines: in KarMMa-3 (66% triple-class refractory, 95% daratumumab-refractory), ide-cel was superior to standard regimens [4]; in the final analysis, median PFS was 13.8 vs 4.4 months and the complete response rate was 44% vs 5%, but OS did not differ because 56% of control-arm patients crossed over to ide-cel [26]. In CARTITUDE-4 (lenalidomide-refractory), cilta-cel achieved a 12-month PFS of 75.9% vs 48.6%, and 60.6% of patients achieved MRD negativity [5]; in the updated analysis with a median follow-up of 33.6 months, the HR for progression or death was 0.29 and OS was also improved [25].
- Bispecific antibodies: in MajesTEC-1 (median of five prior lines of therapy), teclistamab produced an ORR of 63.0%, a median DOR of 18.4 months, MRD negativity in 26.7% and a median PFS of 11.3 months [6]. In MagnetisMM-3 (no prior BCMA-directed therapy), elranatamab produced an ORR of 61.0%, and 35.0% achieved a complete response or better; switching responders to every-2-week dosing reduced grade 3–4 adverse events from 58.6% to 46.6% [7]. With talquetamab, the response rates at the two recommended doses were 70% and 64% [8].
- Toxicity management: the EHA-EMN guideline (2025) provides updated recommendations for managing CRS and ICANS caused by T-cell–redirecting therapies [19].
Treatment regimens and dosing (for physicians)
Treatment regimens and doses: index18 regimens
- Lenalidomide (VRd, DRd, quadruplet regimens, KRd, maintenance and smoldering myeloma): antithrombotic prophylaxis is recommended (risk of venous and arterial thrombosis); adjust the dose for creatinine clearance per the label: in 25 mg regimens with CrCl 30–60 mL/min, start at 10 mg once daily (maintenance dose adjustments are given in the notes of the “Lenalidomide maintenance after autologous transplantation” regimen) [30].
- Bortezomib: at least 72 hours between doses; subcutaneous administration at 1.3 mg/m² is approved in the label [31].
- Daratumumab (D-VRd, DRd, DKd and smoldering myeloma): before each dose: acetaminophen 650–1,000 mg, diphenhydramine 25–50 mg and, in combination regimens, dexamethasone 20 mg (the regimen's own dexamethasone replaces it on injection days; the corticosteroid for monotherapy is given in the notes of the smoldering myeloma regimen). Antiviral prophylaxis against herpes zoster from the first week until 3 months after the end of treatment; blood typing and antibody screening before starting (daratumumab interferes with the indirect antiglobulin test) [27].
- Carfilzomib (KRd and DKd): hydration before Cycle 1 doses (especially in patients at risk of tumor lysis syndrome or renal toxicity), dexamethasone 30 minutes to 4 hours before carfilzomib in Cycle 1, and monitoring of potassium and of signs of volume overload and heart failure [33].
- Infection prophylaxis: the EHA-EMN guideline recommends levofloxacin prophylaxis during the first three months of treatment (especially with lenalidomide or pomalidomide) and co-trimoxazole for Pneumocystis prophylaxis [19].
For physicians
High-risk smoldering myeloma: early treatment
High-risk smoldering myeloma: subcutaneous daratumumab (AQUILA) or lenalidomide (E3A06)
High-risk smoldering myeloma (early treatment can be considered; EHA-EMN guideline)
High-risk smoldering myeloma (early treatment can be considered; EHA-EMN guideline)
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Daratumumab (AQUILA) | |||
| Subcutaneous daratumumab | 1,800 mg | SC | Weekly in Weeks 1–8, every 2 weeks in Weeks 9–24, every 4 weeks from Week 25 |
| Lenalidomide (E3A06) | |||
| Lenalidomide | 25 mg once daily | Oral | Days 1–21 every 28 days |
Daratumumab dosing from the FDA label (AQUILA) [27] and results from AQUILA [12]; lenalidomide dosing from E3A06 [23], in which thromboprophylaxis with at least aspirin, at a suggested dose of 325 mg daily, was recommended. Systemic injection-related reactions occurred in 17% of patients in AQUILA [27]. In this setting, daratumumab is given as monotherapy, and the corticosteroid premedication differs from that used with combination regimens: methylprednisolone 100 mg or equivalent 1–3 hours before each dose (a reduction to 60 mg may be considered after the second dose) and oral methylprednisolone 20 mg for 2 days, starting the day after the injection [27].
Evidence: AQUILA (2025)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Newly diagnosed myeloma: transplant-eligible patients
D-VRd followed by autologous transplantation and D-R maintenance (PERSEUS trial)
Newly diagnosed myeloma in patients eligible for autologous transplantation (up to 70 years of age in PERSEUS)Each drug’s schedule in the table
Newly diagnosed myeloma in patients eligible for autologous transplantation (up to 70 years of age in PERSEUS)
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Induction (Cycles 1–4) and consolidation (Cycles 5 and 6) | |||
| Subcutaneous daratumumab | 1,800 mg | SC | Induction: weekly in Cycles 1 and 2, every 2 weeks in Cycles 3 and 4; consolidation: every 2 weeks |
| Induction and consolidation | |||
| Bortezomib | 1.3 mg/m² | SC | Days 1, 4, 8 and 11, every 28 days |
| Lenalidomide | 25 mg once daily | Oral | Days 1–21, every 28 days |
| Dexamethasone | 40 mg once daily | Oral (IV on daratumumab injection days) | Days 1–4 and 9–12, every 28 days |
| Transplantation | |||
| High-dose melphalan and autologous transplantation | After stem cell collection (after induction) | IV | — |
| Maintenance (Cycle 7 onward) | |||
| Subcutaneous daratumumab | 1,800 mg | SC | Every 4 weeks |
| Lenalidomide | 10 mg once daily (after 3 cycles, 15 mg if tolerated) | Oral | Days 1–28 (continuous) |
Doses from the ClinicalTrials.gov record NCT03710603 and the FDA label for DARZALEX FASPRO [27, 29]; results from PERSEUS [3]. According to the FDA label, the efficacy of daratumumab in the maintenance phase has not been separately established [27], although the EHA-EMN guideline regards the combination of daratumumab and lenalidomide as the new standard for maintenance [19].
Evidence: PERSEUS (2024)
VRd followed by autologous transplantation (IFM 2009 trial)
Newly diagnosed myeloma in transplant-eligible patients (age 65 years or younger in IFM 2009); an acceptable option alongside quadruplet regimens in the EHA-EMN guidelineCycle length: Every 21 days
Newly diagnosed myeloma in transplant-eligible patients (age 65 years or younger in IFM 2009); an acceptable option alongside quadruplet regimens in the EHA-EMN guideline
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Induction: 3 cycles | |||
| Lenalidomide | 25 mg once daily | Oral | Days 1–14 |
| Bortezomib | 1.3 mg/m² | IV (SC is also acceptable in current practice) | Days 1, 4, 8 and 11 |
| Dexamethasone | 20 mg | Oral | Days 1, 2, 4, 5, 8, 9, 11 and 12 |
| Stem cell collection | |||
| Cyclophosphamide + G-CSF | Per institutional protocol | IV | — |
| Transplantation | |||
| Melphalan | 200 mg/m² | IV | Followed by autologous stem cell infusion |
| Consolidation: 2 cycles | |||
| VRd | Same doses, with dexamethasone 10 mg | — | Same days |
Doses from the full text of IFM 2009 [14].
Evidence: IFM 2009 (2017)
Lenalidomide maintenance after autologous transplantation
After autologous transplantation, once hematologic recovery has occurred (neutrophils at least 1,000/mcL and/or platelets at least 75,000/mcL)Cycle length: Every 28 days
After autologous transplantation, once hematologic recovery has occurred (neutrophils at least 1,000/mcL and/or platelets at least 75,000/mcL)
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Lenalidomide | 10 mg once daily; after 3 cycles, 15 mg if tolerated | Oral | Days 1–28 (continuous) |
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Newly diagnosed myeloma: transplant-ineligible patients
VRd (SWOG S0777 trial)
Newly diagnosed myeloma in patients without intent for immediate transplantation
Newly diagnosed myeloma in patients without intent for immediate transplantation
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Induction: 8 cycles | |||
| Bortezomib | 1.3 mg/m² | IV | Days 1, 4, 8 and 11 |
| Lenalidomide | 25 mg once daily | Oral | Days 1–14 |
| Dexamethasone | 20 mg once daily | Oral | Days 1, 2, 4, 5, 8, 9, 11 and 12 |
| Maintenance (Rd, 28-day cycles) | |||
| Lenalidomide | 25 mg once daily | Oral | Days 1–21 |
| Dexamethasone | 40 mg | Oral | Days 1, 8, 15 and 22 |
DRd (MAIA trial)
Transplant-ineligible newly diagnosed myeloma (especially frailer patients); also at relapse after at least one prior line of therapyEach drug’s schedule in the table
Transplant-ineligible newly diagnosed myeloma (especially frailer patients); also at relapse after at least one prior line of therapy
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Daratumumab | 16 mg/kg IV (or 1,800 mg SC on the same schedule) | IV or SC | Weekly in Weeks 1–8, every 2 weeks in Weeks 9–24, every 4 weeks from Week 25 |
| Lenalidomide | 25 mg once daily | Oral | Days 1–21, every 28 days |
| Dexamethasone | 40 mg weekly (age over 75 years or BMI below 18.5: 20 mg) | Oral or IV | Weekly |
Evidence: MAIA (2025)
D-VRd in transplant-ineligible patients (CEPHEUS trial)
Newly diagnosed myeloma, transplant-ineligible or with no planned transplantation; in the EHA-EMN guideline, for patients under 80 years of age without significant frailty
Newly diagnosed myeloma, transplant-ineligible or with no planned transplantation; in the EHA-EMN guideline, for patients under 80 years of age without significant frailty
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Subcutaneous daratumumab | 1,800 mg | SC | Weekly in Weeks 1–6, every 3 weeks in Weeks 7–24, every 4 weeks from Week 25 |
| Cycles 1–8 (21-day) | |||
| Bortezomib | 1.3 mg/m² | SC | Days 1, 4, 8 and 11 |
| Lenalidomide | 25 mg once daily | Oral | Days 1–14 |
| Dexamethasone | 20 mg (age over 75 years or BMI below 18.5: 20 mg on Days 1, 4, 8 and 11) | Oral | Days 1, 2, 4, 5, 8, 9, 11 and 12 |
| Cycle 9 onward (28-day) | |||
| Lenalidomide | 25 mg once daily | Oral | Days 1–21 |
| Dexamethasone | 40 mg (age over 75 years or BMI below 18.5: 20 mg) | Oral | Days 1, 8, 15 and 22 |
Doses from the FDA label for DARZALEX FASPRO (CEPHEUS section) [27]; results from CEPHEUS [24]; place in therapy from the EHA-EMN guideline [19].
Evidence: CEPHEUS (2025)
Isa-VRd (IMROZ trial)
Transplant-ineligible newly diagnosed myeloma, age 18–80 years
Transplant-ineligible newly diagnosed myeloma, age 18–80 years
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Induction: Cycles 1–4 (42-day) | |||
| Isatuximab | 10 mg/kg | IV | Cycle 1: Days 1, 8, 15, 22 and 29; Cycles 2–4: Days 1, 15 and 29 |
| Bortezomib | 1.3 mg/m² | SC | Days 1, 4, 8, 11, 22, 25, 29 and 32 |
| Lenalidomide | 25 mg once daily | Oral | Days 1–14 and 22–35 |
| Dexamethasone | 20 mg | IV on isatuximab days, oral on other days | Days 1, 2, 4, 5, 8, 9, 11, 12, 15, 22, 23, 25, 26, 29, 30, 32 and 33 |
| Continuation: from Cycle 5 (28-day) | |||
| Isatuximab | 10 mg/kg | IV | Cycles 5–17: Days 1 and 15; from Cycle 18: Day 1 |
| Lenalidomide | 25 mg once daily | Oral | Days 1–21 |
| Dexamethasone | 20 mg | IV or oral | Days 1, 8, 15 and 22 |
Doses from the FDA label for SARCLISA (IMROZ section) [32]; results from IMROZ [17]. Premedication 15–60 minutes before isatuximab: dexamethasone (part of the regimen), acetaminophen 650–1,000 mg, an H2 antagonist and diphenhydramine 25–50 mg; antibacterial and antiviral prophylaxis (e.g., against herpes zoster) according to guidelines; isatuximab dose reductions are not recommended [32]. In IMROZ, with 60 months of follow-up, second primary malignancies occurred in 16% vs 9% [32].
Evidence: IMROZ (2024)
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Relapsed myeloma: triplet regimens
KRd (ASPIRE trial)
Relapsed myeloma after 1–3 prior lines of therapy; ASPIRE excluded patients refractory to bortezomib or to lenalidomide-dexamethasone in their most recent regimen, and those with CrCl below 50 mL/min or class III–IV heart failureCycle length: Every 28 days
Relapsed myeloma after 1–3 prior lines of therapy; ASPIRE excluded patients refractory to bortezomib or to lenalidomide-dexamethasone in their most recent regimen, and those with CrCl below 50 mL/min or class III–IV heart failure
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Carfilzomib | Cycle 1, Days 1 and 2: 20 mg/m²; from Day 8 of Cycle 1: 27 mg/m² | IV (over 10 minutes) | Cycles 1–12: Days 1, 2, 8, 9, 15 and 16; Cycles 13–18: Days 1, 2, 15 and 16 |
| Lenalidomide | 25 mg once daily | Oral | Days 1–21 |
| Dexamethasone | 40 mg | Oral or IV | Days 1, 8, 15 and 22 |
PVd (OPTIMISMM trial)
Relapsed myeloma after 1–3 prior regimens, including at least 2 consecutive cycles of lenalidomide; ECOG PS 0–2Cycle length: Every 21 days
Relapsed myeloma after 1–3 prior regimens, including at least 2 consecutive cycles of lenalidomide; ECOG PS 0–2
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Pomalidomide | 4 mg once daily | Oral | Days 1–14 |
| Bortezomib | 1.3 mg/m² | IV or SC | Cycles 1–8: Days 1, 4, 8 and 11; from Cycle 9: Days 1 and 8 |
| Dexamethasone | 20 mg (age over 75 years: 10 mg) | Oral | On each bortezomib day and the day after |
DKd (daratumumab + carfilzomib + dexamethasone; CANDOR trial)
Relapsed myeloma after 1–3 prior lines of therapy; one of the EHA-EMN preferred triplet combinations at first relapse; CANDOR excluded patients with moderate to severe asthma, COPD with FEV1 below 50% and active heart failureCycle length: Every 28 days
Relapsed myeloma after 1–3 prior lines of therapy; one of the EHA-EMN preferred triplet combinations at first relapse; CANDOR excluded patients with moderate to severe asthma, COPD with FEV1 below 50% and active heart failure
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Carfilzomib | Cycle 1, Days 1 and 2: 20 mg/m²; then 56 mg/m² | IV (over 30 minutes) | Days 1, 2, 8, 9, 15 and 16 |
| Intravenous daratumumab | Cycle 1, Days 1 and 2: 8 mg/kg; then 16 mg/kg | IV | Cycle 1: Days 8, 15 and 22; Cycle 2: weekly; Cycles 3–6: Days 1 and 15; then Day 1 |
| Dexamethasone | 20 mg on carfilzomib days and 40 mg on Day 22 | Oral or IV | Days 1, 2, 8, 9, 15, 16 and 22 |
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
Dosing of bone-protecting drugs
Zoledronic acid
All patients with newly diagnosed myeloma requiring treatment, with or without bone lesions (IMWG preferred agent)Cycle length: Every 3–4 weeks
All patients with newly diagnosed myeloma requiring treatment, with or without bone lesions (IMWG preferred agent)
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Zoledronic acid | 4 mg (CrCl above 60); 50–60: 3.5 mg; 40–49: 3.3 mg; 30–39: 3 mg | IV (over at least 15 minutes) | Every 3–4 weeks |
Dose and renal adjustment from the FDA label [40]: measure creatinine before each dose and stop treatment if renal function worsens; not recommended in severe renal impairment; calcium supplement 500 mg and a multivitamin containing 400 IU of vitamin D daily. Place in therapy from the IMWG guideline [9]. Dental examination before starting, and avoidance of invasive dental procedures during treatment (risk of osteonecrosis of the jaw) [40]; in the head-to-head trial, osteonecrosis of the jaw occurred in 4% with denosumab and 3% with zoledronic acid [18].
Denosumab
Myeloma with bone disease; a suitable option, especially in renal impairmentCycle length: Every 4 weeks
Myeloma with bone disease; a suitable option, especially in renal impairment
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Denosumab | 120 mg | SC | Every 4 weeks |
Dose from the FDA label [41]; calcium and vitamin D to prevent or treat hypocalcemia [41]. In the head-to-head trial (denosumab 120 mg SC vs zoledronic acid 4 mg IV every 4 weeks), denosumab was non-inferior, with less renal toxicity (10% vs 17%) but more hypocalcemia [18]. Place in therapy from the IMWG guideline [9].
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
CAR T-cell therapy and bispecific antibodies: dosing and monitoring (for physicians)
For physicians
| Feature | CAR-T (ide-cel, cilta-cel) | Bispecifics (teclistamab, elranatamab, talquetamab) |
|---|---|---|
| Preparation | Requires cell manufacturing (several weeks) and bridging therapy | Off-the-shelf |
| Treatment duration | Single infusion | Continuous until progression or intolerance (dosing frequency can be reduced) [7] |
| Cytokine release syndrome | 88% with ide-cel (5% grade 3 or higher) [4]; 76.1% with cilta-cel (1.1% grade 3–4) [5] | 72.1% with teclistamab (0.6% grade 3) [6]; 57.7% with elranatamab (no grade 3–4) [7] |
| Distinctive toxicities | Cranial nerve palsy in 9.1% and peripheral neuropathy in 2.8% with cilta-cel [5] | Infections: 76.4% (44.8% grade 3–4) with teclistamab [6]; skin and nail toxicities and dysgeusia with talquetamab [8] |
- Bispecific antibodies: step-up doses only with premedication and hospitalization as specified in each drug's label (details under each regimen) [37, 38, 39].
- Infection and hypogammaglobulinemia (CAR-T and bispecifics): anti-BCMA therapies cause profound hypogammaglobulinemia; IgG monitoring and infection prevention (vaccination, antimicrobial prophylaxis and, in some patients, immunoglobulin replacement) in line with the IMWG consensus are essential [10].
For physicians
Relapsed myeloma: CAR T-cell therapy and bispecific antibodies
Idecabtagene vicleucel (ide-cel; KarMMa-3 trial)
Relapsed or refractory myeloma after at least 2 prior lines of therapy, including an immunomodulatory drug, a proteasome inhibitor and an anti-CD38 antibodyCycle length: Single dose
Relapsed or refractory myeloma after at least 2 prior lines of therapy, including an immunomodulatory drug, a proteasome inhibitor and an anti-CD38 antibody
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Lymphodepletion | |||
| Cyclophosphamide | 300 mg/m² once daily | IV | 3 days |
| Fludarabine | 30 mg/m² once daily | IV | 3 days |
| Idecabtagene vicleucel | 300 to 510 × 10⁶ CAR-positive T cells | IV | Once, 2 days after completion of lymphodepletion |
Ciltacabtagene autoleucel (cilta-cel; CARTITUDE-4 trial)
Relapsed or refractory myeloma after at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory drug, and refractory to lenalidomideCycle length: Single dose
Relapsed or refractory myeloma after at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory drug, and refractory to lenalidomide
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Lymphodepletion | |||
| Cyclophosphamide | 300 mg/m² once daily | IV | 3 days |
| Fludarabine | 30 mg/m² once daily | IV | 3 days |
| Ciltacabtagene autoleucel | 0.5 to 1.0 × 10⁶ CAR-positive viable T cells per kg (maximum 1 × 10⁸) | IV | Once, 2–4 days after completion of lymphodepletion |
Dose and schedule from the FDA label for CARVYKTI [36]: the patient should stay near the treatment center for at least 2 weeks after the infusion and should not drive for 2 weeks. Cranial nerve palsy and peripheral neuropathy are distinctive toxicities of this product [5].
Evidence: CARTITUDE-4 (2023)
Teclistamab monotherapy (MajesTEC-1 trial)
Relapsed or refractory myeloma after several lines of therapy (median of 5 prior lines in MajesTEC-1)Cycle length: Weekly
Relapsed or refractory myeloma after several lines of therapy (median of 5 prior lines in MajesTEC-1)
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Step-up doses | |||
| Teclistamab | 0.06 mg/kg (Day 1), 0.3 mg/kg (Day 4), 1.5 mg/kg (Day 7) | SC | Days 1, 4 and 7 |
| Treatment | |||
| Teclistamab | 1.5 mg/kg | SC | Weekly (at least 5 days apart); after at least 6 months of complete response or better: every 2 weeks |
Per the FDA label for TECVAYLI [37]: hospitalization for 48 hours after step-up doses 1 and 2, and daily monitoring for 48 hours after the first treatment dose; 1–3 hours before the step-up doses and the first treatment dose: dexamethasone 16 mg, diphenhydramine 50 mg and acetaminophen 650–1,000 mg; antiviral prophylaxis against herpes zoster.
Elranatamab monotherapy (MagnetisMM-3 trial)
Relapsed or refractory myeloma after at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibody
Relapsed or refractory myeloma after at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibody
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Step-up doses | |||
| Elranatamab | 12 mg (Day 1), 32 mg (Day 4), 76 mg (Day 8) | SC | Days 1, 4 and 8 |
| Treatment | |||
| Elranatamab | 76 mg | SC | Weekly through Week 24; in responders, every 2 weeks from Week 25; if the response is maintained after 24 weeks on that schedule, every 4 weeks from Week 49 |
Per the FDA label for ELREXFIO [38]: hospitalization for 48 hours after the first step-up dose and for 24 hours after the second step-up dose; about 1 hour before the first three doses: acetaminophen 650 mg, dexamethasone 20 mg and diphenhydramine 25 mg; in hypogammaglobulinemia, consider subcutaneous or intravenous immunoglobulin.
Talquetamab monotherapy (MonumenTAL-1 trial)
Relapsed or refractory myeloma after at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibody
Relapsed or refractory myeloma after at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibody
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Weekly schedule | |||
| Talquetamab | 0.01 mg/kg (Day 1), 0.06 mg/kg (Day 4), 0.4 mg/kg (Day 7); then 0.4 mg/kg weekly | SC | Step-up doses on Days 1, 4 and 7; then weekly (at least 6 days apart) |
| Every-2-week schedule | |||
| Talquetamab | 0.01 (Day 1), 0.06 (Day 4), 0.4 (Day 7) and 0.8 mg/kg (Day 10); then 0.8 mg/kg every 2 weeks | SC | Step-up doses on Days 1, 4, 7 and 10; then every 2 weeks (at least 12 days apart) |
Per the FDA label for TALVEY [39]: hospitalization for 48 hours after all step-up doses; 1–3 hours before each step-up dose: dexamethasone 16 mg, diphenhydramine 50 mg and acetaminophen 650–1,000 mg. Skin and nail toxicities and dysgeusia are characteristic of this drug [8].
Evidence: MonumenTAL-1 (2022)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Scientific evidence
Key studies
15 itemsLenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma
Lenalidomide Maintenance After Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: A Meta-Analysis
Ide-cel vs standard regimens in triple-class-exposed relapsed and refractory multiple myeloma: updated KarMMa-3 analyses.
Talquetamab, a T-Cell–Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma
Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study
Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma
Daratumumab/lenalidomide/dexamethasone in transplant-ineligible newly diagnosed myeloma: MAIA long-term outcomes.
Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS trial.
Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma
Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma
Cilta-cel in lenalidomide-refractory multiple myeloma (CARTITUDE-4): an updated analysis including overall survival from an open-label, multicentre, randomised, phase 3 trial.
Teclistamab in Relapsed or Refractory Multiple Myeloma
Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results
Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma
Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma
Clinical guidelines
5 itemsEHA–EMN Evidence-Based Guidelines for diagnosis, treatment and follow-up of patients with multiple myeloma
International Myeloma Society/International Myeloma Working Group Consensus Recommendations on the Definition of High-Risk Multiple Myeloma.
International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma
Treatment of multiple myeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group
Consensus guidelines and recommendations for infection prevention in multiple myeloma: a report from the International Myeloma Working Group
References
41 referencesShow all references, 22 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11Clinical Course and Prognosis of Smoldering (Asymptomatic) Multiple Myeloma
- 12
- 13International Myeloma Society/International Myeloma Working Group Consensus Recommendations on the Definition of High-Risk Multiple Myeloma
- 14
- 15
- 16
- 17
- 18
- 19
- 20
- 21
- 22
- 23
- 24
- 25
- 26Ide-cel vs standard regimens in triple-class-exposed relapsed and refractory multiple myeloma: updated KarMMa-3 analyses
- 27
- 28DARZALEX (daratumumab) injection, for intravenous use — Prescribing Information
- 29PERSEUS: Daratumumab, VELCADE, Lenalidomide, and Dexamethasone (D-VRd) vs VRd in Previously Untreated Multiple Myeloma Eligible for High-dose Therapy (NCT03710603) — arms and interventions
- 30
- 31VELCADE (bortezomib) for injection — Prescribing Information
- 32
- 33
- 34POMALYST (pomalidomide) capsules — Prescribing Information
- 35
- 36CARVYKTI (ciltacabtagene autoleucel) suspension for intravenous infusion — Prescribing Information
- 37
- 38
- 39
- 40
- 41
This page is based on reputable scientific sources and was last updated on 21 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.