AQUILA: Early intervention with daratumumab extends survival in smouldering MM

Daratumumab reduced progression to multiple myeloma (MM) and prolonged overall survival (OS) in patients with high-risk smouldering MM, representing an opportunity to delay or avoid end-organ damage in these patients.

The phase 3 AQUILA study (NCT03301220) randomised 390 patients with smouldering MM 1:1 to daratumumab or active monitoring [1]. Daratumumab was administered as follows: 1,800 mg subcutaneously, every week in cycles 1 and 2, every 2 weeks in cycles 3 to 6, and every 4 weeks in 28-day cycles until 39 cycles/36 months or confirmed disease progression. The primary outcome was progression-free survival (PFS). Prof. Meletios Dimopoulos (University of Athens, Greece) presented the primary results of the trial.

After a median follow-up of 65.2 months, the primary endpoint was met: median PFS was 41.5 months in the control arm and ‘not reached’ in the daratumumab arm (HR 0.49; 95% CI 0.36–0.67; P<0.001; see Figure). “Daratumumab significantly reduced the risk of progression to MM or death by 51%,” commented Prof. Dimopoulos. The PFS rates at 60 months were 63.1% and 40.8%, favouring the daratumumab arm. The OS rates were 93.0% and 86.9% at 60 months of follow-up (HR 0.52; 95% CI 0.27–0.98). “Thus, early intervention with fixed-duration daratumumab extended OS compared with active monitoring,” said Prof. Dimopoulos. He noted that the benefit of daratumumab appeared to be more pronounced in Mayo 2018 criteria high-risk patients.

Figure: Progression-free survival for daratumumab and active monitoring  [1]



In total, 5.7% of the participants discontinued the daratumumab arm due to treatment-emergent adverse events. No new safety issues were identified with daratumumab monotherapy in this population.

“AQUILA strongly favoured early intervention with daratumumab in patients with high-risk smouldering MM,” decided Prof. Dimopoulos. “It offers a chance to improve health outcomes, like survival or delayed progression to MM, in these patients.”

1. Dimopoulos MA, 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. Abstract 773, 66^th ASH Annual Meeting, 7–10 December 2024, San Diego, CA, USA.

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Posted on 29 January 202529 January 2025