Darzalex Faspro Achieves Outstanding Results in Multiple Myeloma with 95% 4-Year PFS

The new data from the PERSEUS and CEPHEUS studies show that DARZALEX FASPRO®-based regimens achieve up to 95% 4-year PFS and over 55% sustained MRD negativity in transplant-eligible patients, and 69% 54-month PFS with 60% MRD negativity in transplant-ineligible patients. Presented at ASCO 2025, the trials highlight deep and durable responses that establish Darzalex Faspro® as a key frontline therapy in NDMM.

Johnson & Johnson announced new data from the Phase 3 PERSEUS and CEPHEUS studies, reinforcing the role of Darzalex Faspro® (daratumumab and hyaluronidase-fihj) as a cornerstone of frontline therapy for patients with newly diagnosed multiple myeloma (NDMM) at the 2025 ASCO Annual Meeting. These studies demonstrate that adding Darzalex Faspro to a bortezomib, lenalidomide, and dexamethasone (VRd) backbone delivers profound, sustained minimal residual disease (MRD) negativity and significantly prolongs progression-free survival (PFS), regardless of transplant eligibility.

PERSEUS: Sustained MRD Negativity in Transplant-Eligible Patients

The PERSEUS study, a randomized Phase 3 trial conducted in collaboration with the European Myeloma Network, evaluated the addition of DDarzalex Faspro to VRd (D-VRd), followed by an investigational maintenance regimen of Darzalex Faspro with lenalidomide (D-R), in transplant-eligible patients. After a median follow-up of nearly four years (47.5 months), more than half of patients receiving the D-VRd and D-R regimen achieved sustained MRD negativity at the 10⁻⁵ sensitivity threshold for at least 24 months (55.8%)—more than double the rate seen with VRd followed by lenalidomide maintenance (22.6%).

This deep response translated into a 95.3% PFS rate at 48 months (95% CI, 0.3–2.3), underscoring the long-term benefits of early, intensive MRD-driven treatment strategies. The data also revealed a marked advantage in 12-month sustained MRD negativity, achieved by nearly two-thirds of patients treated with D-VRd and D-R (64.8% vs. 29.7%; OR=4.42; 95% CI, 3.22–6.08; P<0.0001).

“The data show that D-VRd followed by an investigational D-R maintenance regimen is a highly effective treatment option for transplant-eligible patients with newly diagnosed multiple myeloma. The depth and durability of MRD negativity observed—paired with unprecedented progression-free survival at four years—underscore the long-term benefit the Darzalex Faspro-based regimen can offer patients early in their treatment journey,” said Dr. Philippe Moreau, presenting author and head of Hematology at University Hospital Hôtel-Dieu, France.

CEPHEUS: Benefits in Transplant-Ineligible Patients

The CEPHEUS study focused on transplant-ineligible patients or those for whom transplant was not intended. In this population, the addition of Darzalex Faspro to VRd resulted in impressive MRD-negativity rates and durable PFS improvements, even among older or frail patients.

At a median follow-up of 58.7 months, 60.4% of patients treated with D-VRd achieved overall MRD negativity at the 10⁻⁵ level, compared to 39.3% with VRd alone (OR=2.37; 95% CI, 1.47–3.80; P=0.0004). Deep responses extended to the 10⁻⁶ threshold (45.8% vs. 26.9%; OR=2.28; 95% CI, 1.40–3.73; P=0.0010).

These deeper responses translated into a significant PFS benefit: 69% of patients in the D-VRd arm remained progression-free at 54 months, compared to 48% in the VRd arm (HR=0.51; 95% CI, 0.35–0.74). Overall survival (OS) also numerically favored the D-VRd group (HR=0.66; 95% CI, 0.42–1.03), with an even greater benefit after censoring for COVID-19-related deaths (HR=0.55; 95% CI, 0.34–0.90).

High-Risk Cytogenetics: Subgroup Insights

A subgroup analysis within CEPHEUS further explored outcomes in patients with high-risk cytogenetics. While MRD negativity rates at high risk were similar between treatment arms, the D-VRd regimen provided substantial benefit for patients with standard-risk cytogenetics—reinforcing its consistent efficacy across patient populations.

Safety and Clinical Implications

Both PERSEUS and CEPHEUS reported safety profiles consistent with the known tolerability of Darzalex Faspro. These findings highlight a well-tolerated, effective frontline treatment that drives deep, durable responses and improves long-term outcomes in NDMM.

“Across multiple studies, the growing body of data on DARZALEX-based regimens indicates impressive, deep responses and meaningful progression-free survival in patients with newly diagnosed multiple myeloma, including high risk. These consistent results across patient populations, regardless of transplant eligibility, reinforce the role of Darzalex Faspro as a cornerstone of frontline therapy,” noted Dr. Jordan Schecter, Vice President and Disease Area Leader for Multiple Myeloma at Johnson & Johnson Innovative Medicine.