Clinical trialPhase 3Multiple myeloma

Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma

N Engl J Med · 2019737 patients (368 DRd, 369 Rd)

Facon T, Kumar S, Plesner T, et al. N Engl J Med. 2019. 380:2104-2115

A newer report of this study has been published: Daratumumab/lenalidomide/dexamethasone in transplant-ineligible newly diagnosed myeloma: MAIA long-term outcomes. (2025)

Study type: Clinical trial
Study name: MAIA
Phase: Phase 3
Design: Randomised (1:1), open-label, international multicentre trial
Sample size: 737 patients (368 DRd, 369 Rd)
Source: N Engl J Med · 2019
Trial registration: NCT02252172

In plain words

Many people with myeloma cannot have a stem cell transplant because of their age or other illnesses. This study showed that adding daratumumab to oral treatment with lenalidomide and dexamethasone keeps the disease under control for considerably longer, and with further follow-up it also helped people live longer. This treatment is given without classic chemotherapy and is continued long term; low white blood cell counts and lung infections are a little more common.

Key results

70.6% vs 55.6%

30-month progression-free survival

HR 0.56 (95% CI 0.43–0.73); P<0.001; median follow-up 28.0 months

47.6% vs 24.9%

Complete response or better

P<0.001

24.2% vs 7.3%

MRD negativity (10⁻⁵ threshold)

P<0.001

HR 0.68

Overall survival (2021 update)

95% CI 0.53–0.86; p=0.0013; median follow-up 56.2 months (Lancet Oncol 2021)

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 (DRd)

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 on days 1, 8, 15 and 22. (After a protocol amendment, switching to subcutaneous daratumumab 1800 mg every 4 weeks 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 abstract of the overall survival paper (Lancet Oncol 2021, doi:10.1016/S1470-2045(21)00466-6)

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 who were not candidates for autologous transplantation because of age (65 years and older) or comorbidities.

Endpoints

Primary endpoint: progression-free survival.

Secondary endpoints: complete response or better, MRD negativity, overall survival and safety.

Safety and side effects

The most common grade 3 or 4 adverse events (DRd versus Rd): neutropenia 50.0% versus 35.3%, anaemia 11.8% versus 19.7%, lymphopenia 15.1% versus 10.7% and pneumonia 13.7% versus 7.9%.

Clinical significance and place in guidelines

Based on this study, the FDA approved DRd in 2019 for newly diagnosed transplant-ineligible patients. The overall survival analysis (Facon et al., Lancet Oncol 2021), with a median follow-up of 56.2 months, showed a reduced risk of death (HR 0.68; 95% CI 0.53–0.86; p=0.0013). DRd is one of the preferred first-line regimens for older or frail patients; alongside it, four-drug regimens (Isa-VRd based on IMROZ and D-VRd based on CEPHEUS) are options for transplant-ineligible patients in good general condition.

Limitations

The study was open-label. Treatment continues until disease progression, which matters for cost and cumulative toxicity (infection). The Rd comparator did not include bortezomib, and there was no direct comparison with other three-drug regimens (such as VRd).

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.