Johnson & Johnson announced that the U.S. Food and Drug Administration (FDA) has approved DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) as a single-agent therapy for adults with high-risk smoldering multiple myeloma (HR-SMM). This marks the first and only FDA-approved treatment for HR-SMM, enabling earlier intervention before the disease advances to active multiple myeloma.
The approval is based on results from the Phase 3 AQUILA study (NCT03301220), which compared DARZALEX FASPRO with active monitoring — also known as “watch and wait.” The study demonstrated a 51% reduction in the risk of disease progression or death, significantly improving progression-free survival (PFS). This decision follows the favorable May 2025 vote from the FDA’s Oncologic Drugs Advisory Committee (ODAC) supporting the therapy’s benefit-risk profile.
Smoldering multiple myeloma (SMM) is an asymptomatic precursor to active multiple myeloma, sharing similar genomic characteristics. In 2025, approximately 36,000 new multiple myeloma cases are expected in the U.S., with 15% classified as smoldering, and half of high-risk patients likely to progress to active disease within two years. Currently, the standard approach for HR-SMM is active monitoring without therapeutic intervention.
“Until now, patients with smoldering multiple myeloma had no approved treatment options and could only monitor disease progression,” said Dr. Peter Voorhees, of Atrium Health/Levine Cancer Institute. “The AQUILA study showed that DARZALEX FASPRO significantly delayed disease progression, highlighting the potential of early intervention for high-risk patients.”
After a median follow-up of 65.2 months, 63.1% of patients receiving DARZALEX FASPRO had not progressed to active myeloma at five years, compared to 40.7% in the monitoring group. Among patients classified as high-risk under the Mayo 2018 criteria, median PFS was not reached with DARZALEX FASPRO versus 22.1 months for active monitoring.
Beyond PFS, DARZALEX FASPRO achieved a 63.4% response rate, compared with just 2% in the monitoring group. Patients on DARZALEX FASPRO also experienced a significantly delayed need for first-line multiple myeloma treatment.
“DARZALEX FASPRO is a foundational therapy in multiple myeloma,” said Dr. Jordan Schecter, Vice President, Research & Development, Multiple Myeloma, Oncology, Johnson & Johnson Innovative Medicine. “With this approval, patients with HR-SMM can now receive treatment earlier, changing the way we approach disease management and improving long-term outcomes.”
Adverse reactions in the AQUILA study were consistent with previous DARZALEX FASPRO trials. Common side effects included upper respiratory tract infection, musculoskeletal pain, fatigue, diarrhea, rash, and injection site reactions.
The full AQUILA study results were presented at the 2024 American Society of Hematology (ASH) Annual Meeting and published in The New England Journal of Medicine. A subgroup analysis will be presented at the 2025 ASH Annual Meeting in Orlando, from December 6–9.