Daratumumab Approval May Be “Game Changer” in High-Risk Smoldering Myeloma

In an interview with CancerNetwork^® ahead of the FDA approval of daratumumab and hyaluronidase-fihj (Darzalex Faspro) for adults with high-risk smoldering multiple myeloma, Joseph Mikhael, MD, MEd, FRCPC, FACP, FASCO, discussed how this regulatory decision would signal a “dramatic change” in the treatment field.

Mikhael stated that the approval, along with supporting results from the phase 3 AQUILA trial (NCT03301220), would validate smoldering multiple myeloma as an intermediate area in which patients may benefit from limited therapy with daratumumab. Additionally, he emphasized how the approval would reinforce the importance of shared decision-making between providers and patients regarding “several options” for smoldering multiple myeloma.

Mikhael is the chief medical officer at the International Myeloma Foundation and a professor in the Applied Cancer Research and Drug Discovery Division at the Translational Genomics Research Institute, an affiliate of City of Hope Cancer Center.

Transcript:

If, indeed, this approval goes through, it will be a quite dramatic change in our philosophy and practice in multiple myeloma. For many years, there have been some who have felt that we should almost eliminate the category of smoldering myeloma and simply say someone has MGUS or active myeloma; they either get no treatment or full treatment. But with this most recent clinical trial and the outcomes of it, we realize that there is an in-between. There is an intermediate area where patients may benefit from limited therapy that is not as impactful on their quality of life and delays the progression to active myeloma in a significant majority of patients.

What it heralds to us is validating the notion of having a category of smoldering myeloma, of potentially using daratumumab monotherapy for 3 years as a legitimate treatment for those individuals. But perhaps [it] further underscores the critical importance of a shared decision-making process between the health care team and the patient because there would be several options of that point in a patient’s high-risk smoldering myeloma to decide whether they should have treatment and what treatment, if they should. This would definitely be a significant game changer, as it were, in the high-risk smoldering world.

Reference

FDA approves daratumumab and hyaluronidase-fihj for high-risk smoldering multiple myeloma. News release. FDA. November 6, 2025. Accessed November 6, 2025. https://tinyurl.com/49ks5zkx