Johnson & Johnson’s DARZALEX FASPRO shows 95% survival at 4 years in multiple myeloma

Johnson & Johnson’s oncology-focused drugmaker arm has reported breakthrough data from two pivotal Phase 3 trials—PERSEUS and CEPHEUS—demonstrating the sustained efficacy of DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) across frontline treatment settings for newly diagnosed multiple myeloma (NDMM). Presented as oral abstracts at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago on June 3, the findings spotlight the subcutaneous CD38-directed antibody as a cornerstone therapy in both transplant-eligible and transplant-ineligible populations.

The standout result came from the PERSEUS trial, where transplant-eligible NDMM patients receiving a DARZALEX FASPRO-based quadruplet regimen achieved a 95.3 percent progression-free survival (PFS) at 48 months. Simultaneously, data from the CEPHEUS trial showed a 60.4 percent minimal residual disease (MRD) negativity rate in older or frail transplant-ineligible patients, underscoring the broad utility of the agent in deepening responses and prolonging remission early in the treatment journey.

What do the PERSEUS trial results reveal about long-term myeloma control?

In the PERSEUS study, a DARZALEX FASPRO-based induction and consolidation regimen (D-VRd: daratumumab, bortezomib, lenalidomide, dexamethasone) followed by investigational maintenance therapy with DARZALEX FASPRO and lenalidomide (D-R) led to sustained and deep MRD negativity at both the 12- and 24-month thresholds. At a median follow-up of 47.5 months, 55.8 percent of patients receiving D-VRd followed by D-R achieved 24-month MRD negativity at 10⁻⁵ sensitivity, more than doubling the 22.6 percent rate seen in those treated with standard VRd followed by lenalidomide (R) alone. At 12 months, 64.8 percent of patients in the D-VRd arm achieved MRD negativity compared to 29.7 percent in the VRd arm.

The 48-month PFS of 95.3 percent (95% CI: 0.3–2.3) in the D-VRd cohort represents one of the highest four-year survival rates ever reported in newly diagnosed transplant-eligible multiple myeloma patients. This level of sustained remission and disease control is expected to reshape induction and maintenance paradigms in hematologic oncology.

How does the CEPHEUS trial reinforce frontline value in older patients?

The CEPHEUS trial evaluated the same D-VRd induction approach in transplant-ineligible NDMM patients, many of whom were categorized as frail or high-risk based on Myeloma Geriatric Assessment scores. At a median follow-up of 58.7 months, MRD negativity at 10⁻⁵ was achieved in 60.4 percent of patients treated with D-VRd, compared to 39.3 percent in those receiving VRd alone. At the more stringent 10⁻⁶ threshold, MRD negativity rates were 45.8 percent with D-VRd versus 26.9 percent with VRd.

Clinical outcomes aligned with these deeper responses. PFS at 54 months reached 69 percent in the D-VRd group, compared to 48 percent in the standard arm, with a hazard ratio of 0.51 (95% CI: 0.35–0.74). A favorable trend was also observed in overall survival (OS), with a hazard ratio of 0.66 (95% CI: 0.42–1.03), which further improved after adjusting for COVID-19-related deaths (HR 0.55; 95% CI: 0.34–0.90).

These data highlight DARZALEX FASPRO’s efficacy even among patients with diminished treatment tolerance, where safety, administration route, and duration of response are critical clinical considerations.

How do institutional experts interpret the ASCO 2025 data?

Experts in hematologic malignancies and institutional oncology analysts have noted that the PERSEUS and CEPHEUS findings underscore a “new standard” for early disease intervention. The MRD data, in particular, are being viewed as predictive of long-term outcomes and highly relevant to real-world treatment optimization. The durability of MRD-negative states over 12 and 24 months—with a clear link to superior PFS—strengthens the case for MRD-guided therapy in both academic and community practice.

While the investigational D-R maintenance regimen in PERSEUS has not yet received formal regulatory approval, the strong results have sparked speculation that Johnson & Johnson may pursue additional filings with the U.S. Food and Drug Administration and European Medicines Agency in 2025–2026.

Where does DARZALEX FASPRO stand in the CD38 therapy market?

DARZALEX FASPRO is the only subcutaneous CD38-directed antibody approved to treat multiple myeloma and currently holds nine U.S. FDA approvals, including four in the frontline setting. Its formulation—delivered in minutes and co-formulated with recombinant human hyaluronidase PH20 via Halozyme Therapeutics’ ENHANZE platform—has enabled rapid uptake over the original intravenous DARZALEX.

Johnson & Johnson does not break out revenues by formulation but reported global DARZALEX franchise sales of over $9 billion in 2024. Analysts estimate that DARZALEX FASPRO accounts for a majority of new prescriptions globally, supported by favorable real-world adherence rates and lower administration burden. With more than 618,000 patients treated globally with DARZALEX-based regimens since launch, the franchise continues to dominate CD38-targeted therapy in multiple myeloma.

What are the future implications for myeloma treatment strategy?

Multiple myeloma remains an incurable plasma cell malignancy with approximately 35,000 new diagnoses annually in the United States and over 12,000 disease-related deaths. Despite therapeutic advances, relapsed or refractory disease continues to pose a major clinical challenge, particularly in high-risk cytogenetic groups.

The growing body of evidence around DARZALEX FASPRO points to a shift toward MRD-driven treatment personalization. Across both trials, MRD negativity emerged as a functional proxy for long-term disease control, validating its inclusion as a primary or secondary endpoint in future regulatory submissions. This could influence not only label expansions for DARZALEX FASPRO but also competitive positioning against next-generation agents like BCMA-targeted bispecifics and CAR-T therapies.

Unlike cell-based therapies that may face access and manufacturing constraints, DARZALEX FASPRO offers an off-the-shelf, outpatient-friendly option with consistent efficacy across diverse global populations. It is already included in major treatment guidelines and is reimbursed broadly across North America, Europe, and select Asia-Pacific markets.

What’s next for the PERSEUS and CEPHEUS studies?

The PERSEUS study, conducted by the European Myeloma Network, enrolled 709 transplant-eligible patients across 14 countries in Europe and Australia. The CEPHEUS trial enrolled 396 transplant-ineligible patients across 13 countries and is expected to yield additional subgroup analyses throughout 2025, including those with high-risk cytogenetics and renal impairment.

While both trials were open-label, randomized, and multicenter in design, neither was powered to isolate the effect of DARZALEX FASPRO in the maintenance setting. Still, safety profiles remained consistent with known adverse events, with no new safety signals emerging in either study.

Regulatory watchers expect that Johnson & Johnson will seek formal expansion of the DARZALEX FASPRO label to include maintenance therapy in transplant-eligible patients based on PERSEUS, as well as support broader front-line use in frail or elderly populations using CEPHEUS data. Analysts also anticipate that MRD negativity will be increasingly used by payers as a metric for value-based reimbursement negotiations in oncology.