Higher MRD Negativity Rates Occur with Isa-RD in Older NDMM Population

The median progression-free survival (PFS) was 38.4 months in the isatuximab arm vs 20.2 months in the Rd alone arm.

The addition of isatuximab (Sarclisa) to lenalidomide (Revlimid) and dexamethasone (Isa-Rd) exhibited a significantly higher minimal residual disease (MRD) negativity rate at 10-5vs Rd alone in patients 70 years and older with newly diagnosed multiple myeloma, according to findings from the phase 2 AGMT-MM04 trial (NCT04891809) exhibited in a poster presentation at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition.

Efficacy findings from the phase 2 trial revealed that, after a median follow-up of 14.6 months, among patients treated with Isa-Rd (n = 70) vs Rd (n = 67), the MRD negativity rates were 38.5% vs 2.5%. Additionally, 24.3% vs 9.0% of the respective groups experienced a complete response (CR), and 31.4% vs 19.4% experienced a very good partial response (VGPR) as best response. The time to best response in the respective arms was 7.3 months in both cohorts (P = .78).

The median progression-free survival (PFS) was 38.4 months in the isatuximab arm vs 20.2 months in the Rd alone arm. Additionally, the 24-month PFS rates were 65.8% vs 37.6%, respectively (P = .0094). Furthermore, the median overall survival (OS) was not reached in either arm; the respective 24-month rates were 87.4% vs 72.1% (P = .11).

The median PFS based on cytogenetic risk among both arms was 20.2 months in patients with high-risk disease and 38.4 months in those with standard-risk disease (P = .028). Additionally, patients with detectable circulating tumor cells at day 8 experienced a median PFS of 14.5 months vs 38.4 months among those who did not, with 24-month rates of 25.6% vs 64.3%, respectively (P = .0044).

“Our data show a significantly higher [MRD negativity] rate at 10-5 after 8 cycles of induction therapy with Isa-Rd compared to Rd [at] 38.5% vs 2.5%,” Heinz Ludwig, MD, professor of Medical Oncology/Hematology at the Wilhelminen Cancer Research Institute in Vienna, wrote in the presentation with study coinvestigators. “Additional benefits of Isa-Rd include a higher rate of CR and VGPR [or better], a significantly longer PFS, and a favorable safety and tolerance profile in very [old] patients with [newly diagnosed multiple myeloma].”

A total of 137 were enrolled in the trial, of whom 5 discontinued therapy within the first cycle due to patient or investigator decision for 3 patients, death in 1 patient, and disease progression in another patient. Between cycles 2 and 8, disease progression or death was noted in 3 patients in the Isa-Rd arm and 15 in the Rd arm. Four patients in each arm discontinued due to adverse effects (AEs) or withdrawal of consent.

Patients in the control and experimental arms had a median age of 78 years (range, 70-91) vs 76 years (range, 70-91), and most in either arm were male (53.7% vs 58.6%). The majority of patients had an ECOG performance status of 1 (52.2% vs 50.0%) and standard-risk cytogenetics (55.6% vs 52.2%). A total of 40.3% vs 27.1% had International Staging System (ISS) stage 3 disease.

The most common grade 3 or higher hematologic AEs in the control and experimental arms, respectively, included neutropenia (25.4% vs 27.1%), thrombocytopenia (9.0% vs 2.9%), and anemia (7.5% vs 10.0%). Additionally, the most common grade 3 or higher nonhematologic AEs included infections (26.9% vs 27.1%), pain and discomfort (7.5% vs 8.6%), arrhythmia (6.0% vs 1.4%), injury (4.5% vs 2.9%), and asthenic conditions (4.5% vs 5.7%).

Reference

Ludwig H, Melchardt T, Terpos E, et al. Randomized comparison between isatuximab-rd versus rd induction, followed by isa-R versus R maintenance in very elderly patients with NDMM: efficacy data on MRD after induction (AGMT-MM04 Trial). Blood. 2025;146(suppl 1):2258. doi:10.1182/blood-2025-2258