Pune, India | November 07, 2025
The Food and Drug Administration (FDA) approved daratumumab and hyaluronidaseâfihj (Darzalex Faspro) for adults with high-risk smoldering multiple myeloma. Previously, patients in this category often waited until progression to full multiple myeloma before receiving therapy. Now, earlier intervention becomes possible. According to the FDA’s announcement, the approval stems from the pivotal AQUILA trial, which evaluated the treatment versus active monitoring.
In the randomized trial of 390 patients, those treated with daratumumab and hyaluronidase-fihj received a subcutaneous dose of 1,800 mg/30,000 units initially weekly, then bi-weekly, and eventually every four weeks. Meanwhile, the monitoring arm continued without active therapy until progression. Importantly, the study defined high-risk smoldering multiple myeloma based on one or more specific markers: serum monoclonal protein level above 2 g/dL, involved-to-uninvolved serum-free light chain ratio greater than 20, and bone marrow plasma cells exceeding 20%.
The chief outcome measured was progression-free survival (PFS) as judged by an independent review committee using diagnostic criteria of the International Myeloma Working Group (IMWG). In the active monitoring arm, median PFS reached 41.5 months. Conversely, in the treatment arm, the median PFS was not yet evaluable, yielding a hazard ratio of 0.49 with a 95 % confidence interval of 0.36 to 0.67 and a p-value of less than 0.0001. Clearly, this represents a substantial reduction in risk of progression or death.
Moreover, the prescribing information highlights key safety considerations. Healthcare providers should be vigilant for hypersensitivity and other administration-reaction risks. Additional warnings include cardiac toxicity in patients with light chain amyloidosis, infections, neutropenia, thrombocytopenia, and embryo-fetal toxicity. Also, the treatment can interfere with red blood cell antibody screening and cross-matching. The recommended dose is specified as 1,800 mg of daratumumab combined with 30,000 units of hyaluronidase, administered subcutaneously over approximately three to five minutes.
This approval marks a significant milestone in treating smoldering multiple myeloma, especially for those at high risk of progression. Historically, the standard approach for smoldering disease was surveillance and deferred treatment until overt myeloma developed. With this new option, patients and their physicians may now proactively address the disease earlier in its course. This shift could transform outcomes by delaying or preventing the transition to symptomatic multiple myeloma.
Nonetheless, the new indication applies only to high-risk smoldering multiple myeloma and does not extend to lower-risk categories. The FDA emphasises that the benefit-risk balance has been assessed only for this subgroup. Therefore, accurate risk-stratification remains critical. Physicians must identify eligible patients who meet the defined criteria before prescribing this therapy.
In practical terms, oncologists and hematologists should integrate this approval into shared decision-making with patients who present with smoldering myeloma and meet high-risk markers. They should discuss potential benefits, tolerability, administration logistics, and monitoring needs. Because the therapy is subcutaneous, treatment burden may be lower compared to intravenous regimens. However, safety vigilance remains essential.
In conclusion, daratumumab and hyaluronidase-fihj represent a new standard for the treatment of adults with high-risk smoldering multiple myeloma. This approval could significantly influence patient care by extending progression-free survival and altering the treatment paradigm for this patient population. As providers begin to implement this therapy, ongoing real-world data and longer-term follow-up will ultimately clarify the complete clinical value. Patients and providers should have thoughtful discussions about the benefits and risks of early treatment under this approved indication.
