The approval of daratumumab by the FDA marks a pivotal shift in how we approach high-risk smoldering multiple myeloma—offering new hope and raising important questions about when and how to treat before symptoms even appear. But here’s where it gets controversial… Should we jump into treatment early based on this FDA approval, or are we risking overtreatment in patients who might never develop active disease? And this is the part most people miss: the decision to begin intervention must be made cautiously, in close consultation with patients, given the complexities involved.
Recently, on November 6, 2025, the U.S. Food and Drug Administration approved the subcutaneous formulation of daratumumab (known as Darzalex Faspro), specifically for individuals diagnosed with high-risk smoldering multiple myeloma. This approval was driven by compelling results from the phase 3 AQUILA trial, which demonstrated notable improvements in delaying disease progression. Patients who received daratumumab as monotherapy showed a median progression-free survival (PFS) that was not yet reached at the time of analysis—meaning they remained free of disease progression longer than those on active observation, whose median was approximately 41.5 months. The hazard ratio (HR) of 0.49 with a highly significant P-value (< .0001) underscores the benefit.
Peter Voorhees, MD, a respected professor of cancer medicine at Wake Forest University and a member of the Hematology Department at Atrium Health Levine Cancer Institute, underscores that while this FDA approval is a critical milestone, many questions remain unanswered. In an interview with OncLive®, he pointed out that, although the approval opens new treatment avenues, it does not necessarily dictate a one-size-fits-all approach.
