Landmark Study Shows Daratumumab Significantly Delays Progression in Smoldering Myeloma

New research presented at the 2024 American Society of Hematology (ASH) Annual Meeting demonstrates that early intervention with daratumumab can significantly delay the progression from smoldering multiple myeloma to active disease in high-risk patients.

The phase 3 AQUILA trial, published in the New England Journal of Medicine, showed that patients receiving daratumumab had a 51% lower risk of progression compared to those under active monitoring, the current standard of care.

In this exclusive interview, Dr. Thanos Dimopoulos discusses the groundbreaking results of the AQUILA trial and their implications for patients with high-risk smoldering multiple myeloma. Dr. Dimopoulos explains how this new approach could change the way we think about early intervention in myeloma precursor conditions.

"These results represent a new option for high-risk patients and their physicians to consider when weighing the pros and cons of treatment versus active monitoring," explains Dr. Meletios A. Dimopoulos, lead investigator and professor at the National and Kapodistrian University of Athens School of Medicine.

In early November 2024, the FDA accepted daratumumab for priority review in high-risk smoldering myeloma patients, marking a potential shift in the treatment approach.

Understanding the AQUILA Trial

The international study included 390 patients with high-risk smoldering multiple myeloma (SMM), a precursor condition where patients have more than a 50% risk of developing active myeloma within two years. Participants received either subcutaneous daratumumab for up to three years or underwent active monitoring.

Key findings after 5.5 years of follow-up include:

• 63.1% of daratumumab-treated patients remained progression-free at five years, compared to 40.8% in the monitoring group

• The median time to myeloma progression was not reached in the daratumumab group, while it was 41.5 months in the monitoring group

• Fewer patients needed to start myeloma treatment in the daratumumab group (33%) compared to the monitoring group (52%)

Importantly, patients who received early treatment with daratumumab showed encouraging survival trends, with 93% alive at five years compared to 86.9% in the monitoring group.

How Does Daratumumab Work?

Daratumumab (Darzalex, Johnson&Johnson) is a targeted therapy that works differently from traditional chemotherapy. It's a monoclonal antibody that specifically targets myeloma cells while helping your immune system fight the disease. Learn more about how daratumumab works with Healthtree University.

Safety and Quality of Life

The treatment proved generally well-tolerated. While moderate to severe side effects occurred in 40.4% of treated patients compared to 30.1% in the monitoring group, few patients (5.7%) needed to discontinue treatment. The most common significant side effect was high blood pressure.

"This is the first study to show improved outcomes with an agent that is not chemotherapy in patients with a myeloma-related condition," notes Dr. Dimopoulos.

The treatment's ability to prevent serious complications typically seen at myeloma diagnosis represents a significant advantage for patients.

Looking Ahead

Daratumumab offers several advantages as an early intervention option. Unlike other treatments, it's time-limited (three years) and doesn't cause long-term immunosuppression.

However, Dr. Dimopoulos emphasizes that these findings specifically apply to patients with high-risk SMM. Future research will explore whether combining daratumumab with other medications could further improve outcomes.

The AQUILA trial results suggest that carefully selected high-risk patients may benefit from early intervention, potentially changing the traditional "watch and wait" approach in smoldering myeloma management.

Key Takeaways

• Early treatment with daratumumab may be an option for carefully selected high-risk SMM patients

• The treatment is given for a fixed period of three years

• Regular monitoring and evaluation by specialists is essential

• This approach is specifically for high-risk patients and may not apply to all SMM cases

• Discuss with your healthcare team whether you might be a candidate for this treatment approach

Sources and Further Reading

• Read the full study: Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma

• View the clinical trial details on ClinicalTrials.gov: A Study of Subcutaneous Daratumumab Versus Active Monitoring in Participants With High-Risk Smoldering Multiple Myeloma

• Read the complete ASH 2024 abstract #773

• FDA Review of Daratumumab for High-Risk SMM

• Understanding Smoldering Multiple Myeloma