The risk for disease progression or death was reduced by 51% with subcutaneous Darzalex Faspro in certain patients with smoldering multiple myeloma.
Patients with intermediate- or high-risk smoldering multiple myeloma experienced benefits in progression and survival following treatment with subcutaneous Darzalex Faspro (daratumumab) when compared with active monitoring, study results have shown.
Primary results from the phase 3 AQUILA study were presented at the
Additionally, the greatest benefit was seen among patients with high-risk disease.
Progression-free survival (PFS): the time a patient lives without their disease spreading or worsening.
Overall survival (OS): the time a patient lives, regardless of disease status.
Overall response rate (ORR): patients who responded partially or completely to treatment.
“We believe that with these data, patients with high-risk smoldering myeloma may benefit from immediate treatment with [Darzalex Faspro], and that observation for this particular subset of patients may not be an adequate option,” Dr. Meletios-Athanasios Dimopoulos, professor and chairman, Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Alexandra General Hospital, in Athens, Greece, said during a press briefing at the meeting.
After a median follow-up of 65.2 months, the median progression-free survival (PFS) was not reached (NR) with Darzalex Faspro monotherapy compared with 41.5 months with active monitoring. Further, 60-month PFS rates were 63.1% and 40.8%, respectively, reducing the risk for disease progression or death by 51% with subcutaneous Darzalex Faspro.
“Furthermore, there were fewer patients in the [Darzalex Faspro] arm who progressed with CRAB criteria [12 versus 34, respectively] and with SLiM criteria [50 versus 65]. So not only [did Darzalex Faspro delay] progression, but [patients who received this agent] also avoided a clinically obvious and important type of progression,” Dimopoulos explained.
In total, 15 patients in the Darzalex Faspro arm (7.7%) and 26 patients in the active monitoring arm (13.3%) died. The 60-month overall survival (OS) rates were 93% with Darzalex Faspro compared with 86.9% with active monitoring, reducing the risk for death by 48%. “The majority of deaths were due either to progressive disease during or after the study,” Dimopoulos added.
In addition, Darzalex Faspro monotherapy demonstrated a superior overall response rate (ORR) of 63.4% compared with 2% with active monitoring, with an improved median time to first-line treatment for active myeloma (NR versus 50.2 months, respectively).
Grade 3 (severe) or higher treatment-emergent side effects occurred in 40.4% of patients in the Darzalex Faspro arm compared with 30.1% of those undergoing active monitoring, with the most common being hypertension (5.7% versus 4.6%, respectively). The most common serious treatment-emergent side effect was pneumonia (3.6% versus 0.5%, respectively).
“There were no new safety signals from what we know,” Dimopoulos said. “There was somehow an increased risk of infection, but these were well treated and reversible.”
Eleven patients discontinued Darzalex Faspro treatment due to treatment-emergent side effects, whereas 90 patients underwent dose modifications as a result.
Although observation is the current standard of care for this patient population, Dimopoulos suggested that therapeutic intervention may benefit patients with high-risk disease.
At the meeting, Dimopoulos presented on the primary analysis results from the phase 3 AQUILA study after 36 months of Darzalex Faspro monotherapy compared with active monitoring, aimed at assessing the effect of early intervention to prevent end-organ damage and progression to active disease.
“This is the largest phase 3 trial conducted in patients with high-risk smoldering myeloma,” Dimopoulos noted.
In the open-label, multicenter, randomized phase 3 trial, investigators randomly assigned patients to receive either subcutaneous Darzalex Faspro monotherapy (194 patients) or active monitoring (196 patients) for 36 months or until confirmation of disease progression, whichever occurred first.
Following treatment, patients underwent efficacy follow-up until progression by SLiM-CRAB criteria, with survival follow-up conducted every six months until the end of the study.
Patients were enrolled at 124 sites across 23 countries between Dec. 10, 2017, and May 27, 2019.
The median age was 64 years, and 40.5% of patients were classified as having high-risk disease in accordance with the Mayo 2018 risk criteria. The median time from initial diagnosis of smoldering myeloma to randomization was 0.74 years.
By the clinical cutoff (May 1, 2024), 65.5% and 40.8% of patients in the Darzalex Faspro and active monitoring arms, respectively, completed 36 months of treatment. The most common reason for treatment discontinuation across both arms was progressive disease (21.8% versus 41.8%, respectively).
In November 2024, a supplemental biologics license application was submitted to the FDA, and an extension of indication application was submitted to the European Medicines Agency, for subcutaneous Darzalex Faspro to treat adult patients with high-risk smoldering multiple myeloma based on results from this trial.
“I believe it is important to have an approved therapy, and then based on the practice of the physician and the patient they can make a joint decision whether [the patient] will get the treatment,” Dimopoulos said.
Reference
“Phase 3 Randomized study of daratumumab monotherapy versus active monitoring in patients with high-risk smoldering multiple myeloma: primary results of the Aquila study” by Dr. Meletios-Athanasios Dimopoulos et al., Blood.
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