AQUILA Trial: SC Daratumumab Halves Risk of Progression to Active Myeloma

In an interview with Targeted Oncology, Peter Voorhees, MD, Atrium Health Levine Cancer Institute in Charlotte and Wake Forest University School of Medicine in Winston-Salem, North Carolina, details the landmark efficacy data from the phase 3 AQUILA study (NCT03301220) underpinning the FDA’s recent approval of subcutaneous daratumumab and hyaluronidase-fihj (Darzalex Faspro) for treatment of high-risk smoldering multiple myeloma (HR-SMM).

Watch the first part of Dr Voorhees’ interview.

The AQUILA trial evaluated the efficacy of daratumumab monotherapy vs active monitoring in patients with HR-SMM, defined as those with an approximately 50% chance of developing active multiple myeloma. Patients in the daratumumab arm received the agent for 3 years, while those in the active monitoring arm followed standard protocol. Voorhees noted that patients in both arms underwent rigorous follow-up, ensuring that progression to active disease would be detected early and uniformly, regardless of treatment arm.

The study’s primary end point was progression-free survival (PFS) to active MM, defined by the International Myeloma Working Group (IMWG) SLiM-CRAB criteria. To this end, daratumumab monotherapy was found to significantly reduce the risk of progression to SMM to active MM by 51% (HR, 0.49); this benefit was statistically significant and observed across various subgroups by age, cytogenetics, and performance status.

Furthermore, when applying the IMWG 20/20 criteria for defining HR-SMM, the benefit was even more pronounced (HR, 0.36), indicating that the patients at highest risk of progression derived the greatest PFS benefit.

In terms of the trial’s secondary end points, daratumumab also significantly delayed the need for first-line treatment for active MM; the median time was not reached in the daratumumab arm, compared with 50 months for the active monitoring arm. Secondary analysis regarding PFS on first-line treatment for active MM (PFS2) was also improved in the daratumumab arm.

Although the formal overall survival analysis had not been triggered due to a low number of events, an interim analysis showed that at 5 years, 93% of patients in the daratumumab arm remained alive, compared with 87% in the active monitoring arm (HR, 0.52).

Read the full interview here.