Clinical trialPhase 3Multiple myeloma

Daratumumab/lenalidomide/dexamethasone in transplant-ineligible newly diagnosed myeloma: MAIA long-term outcomes.

Leukemia · 2025737 patients

Facon T, Moreau P, Weisel K, et al. Leukemia. 2025. 39:942-950

Study type: Clinical trial
Study name: MAIA
Phase: Phase 3
Design: Randomised trial (1:1); updated efficacy and safety report after a median follow-up of 64.5 months
Sample size: 737 patients
Source: Leukemia · 2025
Trial registration: NCT02252172

In plain words

This report gives the results of more than five years of follow-up of the MAIA study, in which people with newly diagnosed myeloma who could not have a transplant because of their age or physical condition received either three drugs (daratumumab, lenalidomide and dexamethasone) or two drugs (lenalidomide and dexamethasone). Adding daratumumab almost doubled the time the disease stayed under control (about 62 months versus 34 months), and after five years about two thirds of patients in this group were alive, compared with about half in the other group. This benefit was also seen in older people, even those over 80, and no new side effects were reported.

Key results

61.9 vs 34.4 months

Median progression-free survival

HR 0.55 (95% CI 0.45–0.67); P < 0.0001

Not reached vs 65.5 months

Median overall survival

HR 0.66 (95% CI 0.53–0.83); P = 0.0003

66.6% vs 53.6%

Estimated 60-month overall survival

51.1% vs 30.1%

Complete response or better

P < 0.0001

32.1% vs 11.1%

MRD negativity

P < 0.0001

16.8% vs 3.3%

Sustained MRD negativity (at least 18 months)

P < 0.0001

Drugs in this study:Lenalidomide (Revlimid)Daratumumab (Darzalex)

Dose and schedule cards

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 tableOn the page “Multiple myeloma” · Newly diagnosed myeloma: transplant-ineligible patients

Transplant-ineligible newly diagnosed myeloma (especially frailer patients); also at relapse after at least one prior line of therapy

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

Cycle schedule: Lenalidomide in 28-day cycles; dexamethasone weekly; daratumumab weekly, then every 2 weeks, and every 4 weeks from Week 25
Duration: Until disease progression or unacceptable toxicity

Doses from the FDA labels for DARZALEX and DARZALEX FASPRO; results from MAIA.

On the page “Multiple myeloma” · Newly diagnosed myeloma: transplant-ineligible patients

DRd

Newly diagnosed myeloma, transplant-ineligibleEach drug’s schedule in the tableOn the page “DRd regimen (daratumumab, lenalidomide, dexamethasone) in myeloma”

Newly diagnosed myeloma, transplant-ineligible

Drug	Dose	Route	Schedule
Daratumumab	16 mg/kg IV (or 1800 mg subcutaneous)	IV or subcutaneous	Weekly in cycles 1 and 2; every 2 weeks in cycles 3 to 6; then every 4 weeks
Lenalidomide	25 mg	Oral	Days 1 to 21
Dexamethasone	40 mg (20 mg over 75 years or with a BMI below 18.5)	Oral	Weekly

Cycle schedule: Every 28 days
Duration: Until progression

As in MAIA.

Dose source:.

On the page “DRd regimen (daratumumab, lenalidomide, dexamethasone) in myeloma”

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.

Treatment arms and regimens

1Daratumumab + lenalidomide + dexamethasone (D-Rd)

28-day cycles until disease progression or unacceptable toxicity: daratumumab 16 mg/kg IV weekly in cycles 1 and 2, every 2 weeks in cycles 3 to 6 and then every 4 weeks; lenalidomide 25 mg orally on days 1 to 21; dexamethasone 40 mg weekly (20 mg in patients over 75 years or with BMI below 18.5). After a protocol amendment, switching to subcutaneous daratumumab was allowed.

2Lenalidomide + dexamethasone (Rd)

Lenalidomide 25 mg orally on days 1 to 21 and dexamethasone 40 mg weekly in 28-day cycles until disease progression or unacceptable toxicity.

Source of the regimen details: ClinicalTrials.gov NCT02252172 and the FDA label for DARZALEX (Clinical Studies section, MAIA)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with newly diagnosed multiple myeloma (NDMM) who were ineligible for stem-cell transplantation. This report includes subgroup analyses by age (under 70, 70 to under 75, 75 and older, and 80 years and older).

Endpoints

Primary endpoint: progression-free survival (PFS).

Other endpoints: overall survival, complete response or better, minimal residual disease (MRD) negativity and sustained MRD negativity, and safety; plus age-subgroup analyses.

Safety and side effects

According to the abstract, no new safety concerns were observed with this longer follow-up. Adverse event figures are given in the full text of the paper.

Clinical significance and place in guidelines

This long-term analysis confirms the benefit of D-Rd in progression-free and overall survival in transplant-ineligible patients and shows its benefit across all age groups, including 80 years and older. According to the authors, these results continue to support D-Rd as first-line therapy in this group.

Limitations

This report is an updated analysis of the trial, and the age-subgroup analyses are descriptive. The abstract does not give details of adverse events or doses. The comparator was the two-drug Rd regimen, not newer three-‎ or four-drug regimens.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.