JnJ Darzalex faspro approved by USFDA for high risk smoldering multiple myeloma

FDA approval is based on findings from the AQUILA study ( NCT03301220), which evaluated the efficacy and safety of DARZALEX FASPRO compared to active monitoring (or “Watch and Wait”) in the largest Phase 3 trial in patients with HR-SMM. The AQUILA study demonstrated a significant improvement in the primary endpoint of progression-free survival (PFS), with DARZALEX FASPRO reducing the risk of disease progression to active multiple myeloma or death by 51 percent compared to active monitoring, according to the International Myeloma Working Group (IMWG) diagnostic criteria for multiple myeloma. This follows the May 2025 vote by the U.S. FDA Oncologic Drugs Advisory Committee (ODAC) in favor of the benefit-risk profile of DARZALEX FASPRO as a single agent treatment for patients with HR-SMM.

Smoldering multiple myeloma (SMM) is an asymptomatic malignancy that is genomically the same as active multiple myeloma and where these abnormal cells can be detected in the bone marrow. In 2025, it is estimated that more than 36,000 people will be diagnosed with multiple myeloma in the U.S., and approximately 15 percent of those are classified as smoldering. An estimated 50 percent of patients diagnosed with HR-SMM are likely to progress to active disease within two years of diagnosis. Currently, the standard of care for HR-SMM is active monitoring to track signs of biochemical progression and/or end-organ damage. Recent evidence suggests that people at high-risk of progressing to active multiple myeloma could benefit from earlier therapeutic intervention.

“Until now, patients diagnosed with smoldering multiple myeloma only have the option to watch and wait for any active signs of progression to active disease,” said Peter Voorhees, M.D., Atrium Health/Levine Cancer Institute, Charlotte, N.C. “Results from AQUILA demonstrated DARZALEX FASPRO significantly delayed disease progression, underscoring the role of early disease intervention for patients with high-risk smoldering multiple myeloma.”

The Phase 3 AQUILA study showed after a median follow-up of 65.2 months, 63.1 percent of patients who received DARZALEX FASPRO had not progressed to active myeloma at 5 years (60 months) versus 40.7 percent in the active monitoring group (hazard ratio [HR], 0.49; 95 percent confidence interval [CI], 0.36-0.67; P<0.001). Today, most physicians use the Mayo 2018 criteria (20/2/20) to assess risk status in patients with smoldering myeloma. In a post hoc analysis of AQUILA, 41 percent of patients met the Mayo 2018 HR-SMM classification. Among these patients, median PFS was not reached in the DARZALEX FASPRO arm and was 22.1 months in the active monitoring arm (HR, 0.36; 95 percent CI, 0.23-0.58).

Beyond the primary endpoint of PFS, patients in AQUILA who received DARZALEX FASPRO saw a higher response rate of 63.4 percent compared to 2.0 percent with active monitoring (P<0.001). The median time to patients receiving first-line multiple myeloma treatment was delayed for patients receiving DARZALEX FASPRO compared to active monitoring, with median time to first treatment NR vs 50.2 months for the active monitoring group (HR, 0.46; 95 percent CI, 0.33-0.62).

“DARZALEX FASPRO is a foundational therapy in multiple myeloma and illustrates our commitment to improve outcomes for patients at every stage of their disease,” said Jordan Schecter, M.D., Vice President, Research & Development, Multiple Myeloma, Oncology, Johnson & Johnson Innovative Medicine. “Data from the AQUILA study reinforce the significant impact DARZALEX FASPRO continues to have for patients. With this approval, patients with HR-SMM will now be able to receive this treatment before they progress to active multiple myeloma, giving us the opportunity to shift the treatment paradigm and bring hope to people who are impacted by this disease.”

Results from AQUILA were first presented at the 2024 American Society of Hematology (ASH) Annual Meeting and simultaneously published in The New England Journal of Medicine. A subgroup analysis from the AQUILA study, evaluating the efficacy and safety of DARZALEX FASPRO monotherapy in patients with HR-SMM using IMWG 2020 and IMWG 2020 plus cytogenetic risk models, will be presented at the 2025 ASH Annual Meeting in Orlando from December 6-9.