AQUILA Trial: Closing the Care Gap in High-Risk Smoldering Multiple Myeloma

In an interview with Targeted Oncology, Peter Voorhees, MD, of Atrium Health Levine Cancer Institute in Charlotte and Wake Forest University School of Medicine in Winston-Salem, North Carolina, pinpoints the treatment gap in high-risk smoldering multiple myeloma (HR-SMM) that the phase 3 AQUILA study (NCT03301220) of subcutaneous daratumumab and hyaluronidase-fihj (Darzalex Faspro) sought to address, ultimately resulting in the agent’s November 2025 approval for HR-SMM treatment.

Read the full interview here.

Prior to the AQUILA study, there was no clear standard of care nor regulatory approvals for therapy for SMM. The lingering, motivating question at the time was whether intervention prior to the development of active multiple myeloma (MM), rather than after its development, was valuable for long-term clinical outcomes.

Voorhees details 2 precursor randomized trials in patients with SMM that supported this path of investigation, as follows:

1. The phase 3 QUIREDEX study (NCT00480363): Conducted by the Spanish Myeloma Group, this trial compared combination therapy of lenalidomide (Revlimid) with dexamethasone for 2 years vs active monitoring, showing that lenalidomide treatment reduced the risk of progression to active MM and even conferred an overall survival advantage.
2. The phase 3 ECOG-ACRIN study (NCT01169337): Comparing lenalidomide monotherapy vs active monitoring, this trial also demonstrated a reduction in the risk of progression to active MM, showing that patients with HR-SMM derived the most benefit.

These trials set the stage for the AQUILA trial and established the target population for the trial and FDA approval: those who have a 50% likelihood of developing active MM during the first 2 years of monitoring.