Daratumumab monotherapy demonstrated benefit versus active monitoring among patients with high-risk smoldering multiple myeloma (MM), according to phase 3 data from the Aquila study presented by Meletios-Athanasios Dimopoulos, MD, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece.

Dr Dimopoulos presented these results at the 66^th ASH Annual Meeting in San Diego, California.

“Daratumumab monotherapy was well-tolerated and demonstrated a clinically meaningful and significant benefit in preventing or delaying progression to active MM compared with active monitoring in patients with high-risk smoldering multiple myeloma,” wrote Dr Dimopoulous and colleagues.

“These results strongly support the benefit of early intervention with daratumumab monotherapy versus active monitoring, the current standard of care, in patients with high-risk SMM,” they added.

Transcript:

I'm Thanos Dimopoulos, I am a professor of hematology and medical oncology at the University of Athens in Athens, Greece and I'm here in San Diego for the 2024 American Society of Hematology annual meeting. 

In this meeting I presented the primary analysis of the Aquila trial, this is a prospective randomized study which included 300 patients with high risk smoldering multiple myeloma who were randomized to receive either daratumumab as a single agent or to be on active surveillance.

Patients were very well staged before inclusion in the study with modern imaging technique to make sure that there were no occult asymptomatic bone lesions. Subsequently the patients were followed closely every 12 weeks with blood and urine studies, and also every year with imaging techniques and every two years with bone marrow. 

The main observation of this study was that the administration of daratumumab decreased by 50% the probability of progression to symptomatic myeloma or death compared to control. Furthermore, there were fewer patients who progressed with symptomatic bone lesions, renal impairment, or severe anemia when they received daratumumab. 
Also, the overall survival analysis indicated that there was a survival benefit in favor of daratumumab treated patients with a hazard ratio of 0.5. Daratumumab was very well tolerated and only 5% of the patients discontinued treatment because of side effects.

Taking all this data together, I believe that this is a practice-changing study, and when daratumumab is approved by regulatory authorities I believe that many patients with asymptomatic smoldering but high-risk feature multiple myeloma may benefit from treatment with this agent.

Source:

Dimopoulos MA, Voorhees P, Schjesvold F, et al. Phase 3 Randomized Study of Daratumumab Monotherapy Versus Active Monitoring in Patients with High-Risk Smoldering Multiple Myeloma: Primary Results of the Aquila Study. Presented at the 66^th ASH Annual Meeting & Exposition; December 7, 2024; San Diego, California. Abstract 773.