Dr Burke Discusses Daratumumab in Smoldering Myeloma

In this month's Chief Insights in Oncology, John M. Burke, MD, hematologist-oncologist at Rocky Mountain Cancer Centers and editor-in-chief of Targeted Therapies in Oncology, discusses his column on the FDA's Oncologic Drugs Advisory Committee (ODAC) meeting held in May 2025 discussing the use of daratumumab (Darzalex) for the treatment of high-risk smoldering multiple myeloma.

The ODAC voted 6 to 2 that results from the AQUILA study (NCT03301220) provides sufficient evidence to support a favorable benefit-risk ratio for subcutaneous daratumumab for patients with high-risk smoldering multiple myeloma (SMM).

"[AQUILA] is a big trial, 390 patients with high risk, defined fairly broadly. The outcomes were that patients who were treated, as opposed to not treated, had improved progression-free and overall survival," Burke says. "It's not a big surprise that progression-free survival was improved. It's fairly easy to do that at a trial where you're treating patients vs not treating patients.... What was more interesting was that there is definitely a trend toward improved overall survival."

Daratumumab is an approved therapy for several myeloma indications, and this new proposed indication is for the treatment of adult patients with high-risk SMM, a precursor condition that is typically asymptomatic. Patients with high-risk SMM have a 5-year risk of progression to multiple myeloma of about 80%, according to recent models. There are no approved therapies for SMM, and a watch-and-wait strategy is typically employed.

While the FDA has yet to approve daratumumab for this indication, the ODAC's positive vote is a positive signal.

"It's a little tough to know how to apply this to practice, because... if you treat everyone with smoldering myeloma, you're going to wind up treating a whole bunch of patients that would not need any therapy for many years. And the toxicities of daratumumab appear to be relatively manageable and consistent, largely of infections and fatigue," Burke adds.

Check out the full interview with Dr Burke on YouTube.

REFERENCE:

Meeting of the Oncologic Drug Advisory Committee. FDA. May 20, 2025. Accessed July 24, 2025. https://tinyurl.com/5n7mwvjt