The US Food and Drug Administration (FDA)’s Oncologic Drugs Advisory Committee (ODAC) voted 6-2 that the results from the phase 3 AQUILA trial support a favorable benefit-risk profile for daratumumab and hyaluronidase-fihj (DARZALEX FASPRO) in patients with high-risk smoldering multiple myeloma (SMM).
The phase 3 AQUILA trial randomly assigned patients with high-risk SMM to receive either subcutaneous daratumumab monotherapy or active monitoring.
The panel considered whether the AQUILA trial provided sufficient evidence to support use of the subcutaneous anti-CD38 monoclonal antibody in a population with no current approved treatment and a high risk of progression to symptomatic disease.
“All the endpoints effectively are favoring the intervention here,” said Daniel Spratt, MD, who, while acknowledging concerns for patient over treatment, said the survival differences are meaningful. Dr. Spratt also asked the FDA to define what qualifies as “high risk” and asked the sponsor continue to track the data so that the overall survival outcomes can continue to mature.
In contrast, Neil Vasan, MD, PhD, an oncologist at the Columbia University Herbert Irving Comprehensive Cancer Center, who voted no, expressed concern about overtreatment.
“The reason I voted no was that I felt that this bimodal distribution within the population—that there is a group of patients that we’re overtreating, a group of patients that we’re undertreating—we don’t really have great data right now to understand who those people are, so that drove my vote,” Dr. Vasan said. “I agree with Dr. Spratt’s comments about if this does result in approval to have clear indications in the package label about how this is thought of and how we think about high risk.”
Daratumumab demonstrated a clinically meaningful and statistically significant benefit compared with active monitoring, the current standard of care for high-risk SMM. Data from the trial showed delayed disease progression and a trend toward overall survival benefit.
“High-risk smoldering multiple myeloma remains a challenging clinical conundrum with no approved therapies, and earlier intervention may delay or even prevent progression to active multiple myeloma,” said Peter Voorhees, MD, of Atrium Health / Levine Cancer Institute in Charlotte, North Caroline, in a Janssen press release. Voorhees, who did not vote on the FDA panel, was an AQUILA trial investigator. “We appreciate the balance the committee provided when assessing the risks and benefits of finite treatment at this stage and its recognition of the promise of DARZALEX FASPRO.”
The FDA is expected to make a final decision based on the panel’s recommendation in the coming months.
