Dr Anderson on Daratumumab/Lenalidomide Maintenance After ASCT in Newly Diagnosed Myeloma

“With 40.3 months of follow up, the progression-free survival favored the [daratumumab and lenalidomide (DR)] cohort over [lenalidomide] alone. The hazard ratio was 0.55, and the 36-month PFS was 76.8% [in the DR arm].”

Larry Anderson, MD, PhD, professor of internal medicine at UT Southwestern Medical Center, discussed updated efficacy and safety findings from the phase 3 AURIGA study (NCT03901963), which evaluated daratumumab and hyaluronidase-fihj (Darzalex Faspro; subcutaneous daratumumab) in combination with lenalidomide (Revlimid) compared with lenalidomide alone as maintenance therapy in patients with newly diagnosed multiple myeloma following autologous stem cell transplant (ASCT).

At a median follow-up of 40.3 months, subcutaneous daratumumab plus lenalidomide demonstrated clinically meaningful improvements in minimal residual disease (MRD) conversion and progression-free survival (PFS) without added toxicity, Anderson said.

Findings from AURIGA presented at the 22nd Annual International Myeloma Society m/eeting and Exposition showed that subcutaneous daratumumab plus lenalidomide more than doubled the overall MRD-negative conversion rate compared with lenalidomide alone and improved sustained MRD negativity across key subgroups, he noted. The 6-month sustained MRD-negativity rate more than doubled with subcutaneous daratumumab plus lenalidomide, and the sustained MRD-negativity rate for at least 12 months was nearly quadrupled, Anderson added. At 36 months, the PFS rate was 76.8% with subcutaneous daratumumab plus lenalidomide vs 55.6% with lenalidomide alone, corresponding to a 45% reduction in the risk of disease progression or death (HR, 0.55; 95% CI, 0.33-0.91; P = .0183).

Regarding safety, the incidence of grade 3/4 treatment-emergent adverse effects (TEAEs) was similar between treatment arms, observed in 49.0% of patients in the subcutaneous daratumumab plus lenalidomide arm and 45.9% of those in the lenalidomide alone arm, Anderson said. Neutropenia was the most common grade 3/4 TEAE, occurring in 19.4% of patients who received subcutaneous daratumumab plus lenalidomide and 7.1% of those who received lenalidomide alone. Rates of infections, serious TEAEs, and treatment discontinuations due to AEs were also comparable, and no new safety concerns were observed, he added.

Although overall survival (OS) data remain immature, an early trend favoring subcutaneous daratumumab plus lenalidomide has emerged, Anderson noted. At the time of the analysis, the estimated 36-month OS rate was 94.7% in the subcutaneous daratumumab plus lenalidomide arm compared with 90.5% in the lenalidomide-alone arm (HR, 0.42; 95% CI, 0.14-1.20).

Anderson concluded that the addition of subcutaneous daratumumab to lenalidomide maintenance significantly improved MRD conversion and PFS without increasing toxicity. These results, he said, support subcutaneous daratumumab plus lenalidomide as a more effective post-transplant maintenance approach than lenalidomide alone in patients with newly diagnosed multiple myeloma, with the potential to translate into improved long-term survival.