The FDA has approved daratumumab and hyaluronidase (DARA SC; Darzalex Faspro, Janssen Biotech) for adults with high-risk smoldering multiple myeloma (SMM).

The approval makes DARA SC, a subcutaneous injection already on the US market as a standard first-line option for MM, the first medication approved for SMM, an MM precursor.

Until now, the standard treatment for SMM was either watchful waiting or referral to a clinical trial.

Approval was based on the open label phase 3 AQUILA trial in 390 SMM patients at high-risk for progression to MM.

AQUILA randomized 194 patients to DARA SC and 196 to active monitoring. DARA SC subjects received 1800 mg daratumumab/30,000 units hyaluronidase once a week from 2 months, then once every 2 weeks out to 2 years, followed by once a month up to month 36.

At 5 years, MM progression free survival was 63.1% with DARA SC vs 40.8% with active monitoring; 5-year overall survival was 93.0% with DARA SC vs 86.9%.

The trial was considered at a meeting of FDA’s Oncologic Drugs Advisory Committee in May.

The agency was concerned that AQUILA, which was designed about 10 years ago, used an outdated model to select patients as high-risk for progression.

With current risk models, FDA said only 41% of participants in the trial would be categorized as high-risk, raising “concerns regarding the applicability of the trial results to a population with high-risk SMM, as currently defined.”

The agency was also concerned about unnecessary treatment because not all high-risk patients progress to MM. As a result, some patients could face the risk of treatment — cardiac toxicity, infections, neutropenia, thrombocytopenia, embryo-fetal toxicity, and other issues — with no benefit. 

Janssen’s parent company, Johnson and Johnson, countered that all of AQUILA’s end points were positive, and that without an approved medication for SMM, patients are left powerless as they wait for MM to emerge, something a commenter likened to “sitting on a ticking time bomb.”

In the end, ODAC voted six to two in favor of approval, judging that the risk-benefit profile of DARA SC for SMM is favorable and because panelists wanted physicians and patients to have a treatment option for SMM.

The recommended dose is 1800/30,000 units administered subcutaneously over approximately 3-5 minutes.

The price of one dose is $10,334.50, according to drugs.com.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape Medical News. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com.