Daratumumab Regimen Shows Continued Efficacy in Transplant-Ineligible NDMM

Combining daratumumab (Darzalex) with lenalidomide (Revlimid) and dexamethasone (D-Rd) demonstrated sustained improvements in progression-free survival (PFS) and overall survival (OS) vs Rd alone among patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for transplant, according to updated findings from the phase 3 MAIA trial (NCT02252172) published in Leukemia.¹

After a median follow-up of 64.5 months (range, 0-77.6) across the intent-to-treat (ITT) population, the median PFS was 61.9 months with D-Rd vs 34.4 months with Rd (HR, 0.55; 95% CI, 0.45-0.67; P <.0001). The estimated 60-month PFS rate was 52.1% and 29.6% in each respective arm. D-Rd improved PFS in patients younger than 70 (HR, 0.35; 95% CI, 0.21-0.56; P <.0001), 70 to 74 years old (HR, 0.64; 95% CI, 0.45-0.89; P = .0079), 75 years and older (HR, 0.59; 95% CI, 0.44-0.79; P = .0003), and 80 years and older (HR, 0.48; 95% CI, 0.31-0.76; P = .0011).

The median OS was not reached (NR) with D-Rd compared with 65.5 months using Rd (HR, 0.66; 95% CI, 0.53-0.83; P = .0003), with estimated 60-month rates of 66.6% vs 53.6% in each arm. OS improved in the D-Rd arm among patients younger than 70 (HR, 0.50; 95% CI, 0.27-0.90; P = .0179), 70 to 74 years old (HR, 0.64; 95% CI, 0.43-0.96; P = .0274), 75 years and older (HR, 0.75; 95% CI, 0.55-1.02; P = .0671), and 80 years and older (HR, 0.71; 95% CI, 0.44-1.14; P = .1574).

In the D-Rd and Rd arms, respectively, the objective response rate (ORR) was 92.9% vs 81.6% (P <.0001), the complete response (CR) or better rate was 51.1% vs 30.1% (P <.0001), the very good partial response (VGPR) or better rate was 81.5% vs 56.9% (P <.0001), and the minimal residual disease (MRD)–negative rate was 32.1% vs 11.1% (P <.0001). Among patients with a CR or better, median PFS was NR with D-Rd and Rd (HR, 0.52; 95% CI, 0.35-0.76; P = .0007), and median OS was NR in both arms (HR, 0.58; 95% CI, 0.37-0.91; P = .0164).

“This updated analysis of MAIA, with a median follow-up of 64.5 months, confirmed results of the primary efficacy analysis and the interim OS analysis, which demonstrated statistically significant and clinically meaningful improvement in PFS and OS with D-Rd vs Rd treatment until disease progression in transplant-ineligible patients with NDMM,” lead study author Thierry Facon, MD, a professor in the Department of Hematology at Lille University Hospital in Lille, France, and a member of the French Academy of Medicine, wrote with study coauthors.¹ “These results, comprising the longest follow-up of MAIA with a complete dataset, together with the OS benefit observed with daratumumab-containing regimens in the ALCYONE [NCT02195479], CASSIOPEIA [NCT02541383], CASTOR [NCT02136134], and POLLUX [NCT02076009] studies continue to support the use of daratumumab in patients with [multiple myeloma].”

In the open-label phase 3 MAIA study, 737 patients were randomly assigned 1:1 to receive D-Rd (n = 368) or Rd alone (n = 369). All patients received lenalidomide at 25 mg or 10 mg orally if the patient’s creatine clearance was 30 to 50 ml per minute on days 1 to 21 plus dexamethasone at 40 mg or 20 mg if the patient was older than 75 or had a body mass index of less than 18.5 kg/m² on days 1, 8, 15, and 22. Additionally, investigators administered daratumumab at 16 mg/kg intravenously once weekly during cycles 1 and 2, every 2 weeks from cycles 3 to 6, and every 4 weeks afterwards to patients in the D-Rd arm.

The trial’s primary end point was PFS. Secondary end points included CR rate, stringent CR rate, ORR, MRD-negativity rate, PFS on next line of therapy, and OS.

Patients with documented NDMM, an ECOG performance status of 0 to 2, and ineligibility to undergo high-dose chemotherapy with autologous stem cell transplant because of age or comorbidities were able to enroll on the study. Baseline characteristics were balanced between the D-Rd and Rd arms.

Investigators administered subsequent therapy to 35.2% of those in the D-Rd arm and 53.2% of the Rd arm. Median PFS among patients who received a subsequent line of therapy was 73.7 months vs 48.9 months in each respective arm (HR, 0.61; 95% CI, 0.49-0.76; P <.0001).

Grade 3/4 treatment-emergent adverse effects (TEAEs) were reported in 95.9% and 88.8% of the D-Rd and Rd arms, respectively. The most common grade 3/4 TEAEs in each arm included neutropenia (54.1% vs 37.0%), pneumonia (19.5% vs 10.7%), and anemia (17.0% vs 21.6%).

Overall, TEAEs resulted in treatment discontinuation among 14.6% of the D-Rd arm and 23.8% of the Rd arm. Deaths due to TEAEs occurred in 9.9% and 9.3% of patients, respectively. The incidence of grade 3/4 TEAEs and serious TEAEs was similar for D-Rd and Rd in subgroups of patients who were 75 years and older or 80 years and older.

Post hoc analysis findings from the MAIA trial that investigators recently published in the European Journal of Haematology showed that D-Rd improved health-related quality of life outcomes vs Rd.²

References

1. Facon T, Moreau, P, Weisel K. et al. Daratumumab/lenalidomide/dexamethasone in transplant-ineligible newly diagnosed myeloma: MAIA long-term outcomes. Leukemia. Published online February 27, 2025. doi:10.1038/s41375-024-02505-2
2. Perrot A, Facon T, Plesner T, et al. Sustained improvement in health-related quality of life in transplant-ineligible newly diagnosed multiple myeloma treated with daratumumab, lenalidomide, and dexamethasone: MAIA final analysis of patient-reported outcomes. Eur J Haematol. Published online February 14, 2025. doi:10.1111/ejh.14392