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AQUILA

Smoldering Myeloma

AQUILA

Manufactured by: Janssen Biotech, Inc.
Product name: DARZALEX® (Daratumumab)

About the AQUILA Trial

The AQUILA trial is a Phase 3 randomized study evaluating daratumumab (brand name DARZALEX®, manufactured by Janssen Biotech, Inc., a Johnson & Johnson company) versus active monitoring in patients with high-risk smoldering multiple myeloma (SMM). Involving 390 patients and a median follow-up of 5.5 years, the study demonstrated that daratumumab significantly prolonged progression-free survival (63.1% vs. 40.8%) and showed a favorable trend in overall survival (93% vs. 87%) compared to monitoring alone. Daratumumab was well tolerated, with no major quality of life impairment reported. These results, presented at ASH 2024 by  Dr. Meletios Dimopoulos, suggest daratumumab may play a pivotal role in delaying progression in high-risk SMM.

Table of Contents

Major Presentations and Milestones

AQUILA Trial design, results, and conclusions

AQUILA Sentiments and Criticisms

AQUILA Temporal Sentiment Arc

Professional Resources : Interactive Tweet History, Influence Diagram, Sentiment Table, AI Chatbot

AQUILA Trial: Major Presentations and Milestones

Primary speakers driving the story

ASH 2024: Primary analysis dissemination and rapid KOL interpretation.

Source: https://x.com/VincentRK/status/1866205046855377366

NEJM publication (May 2025): Publication milestone and circulation of key endpoints.

Source: https://x.com/NEJM/status/1920463768926237132

ASH 2025 cycle (“#ASH25”): Follow-on discussion emphasizing risk stratification and “treat vs observe” implementation pathways.

Source: https://x.com/VincentRK/status/1993402192103956908

AQUILA Trial Design, Results, and Conclusions

Trial Design:

  • Phase 3, randomized 1:1; N=390; enrollment Dec 2017–May 2019 across 124 sites in 23 countries.
  • Population: high-risk smoldering multiple myeloma.
  • Arms: daratumumab subcutaneous monotherapy (fixed duration) vs active monitoring.
  • Primary endpoint: PFS by independent review committee per IMWG SLiM-CRAB criteria.
  • Key secondary endpoints: ORR, time to first-line treatment for MM, PFS on first-line treatment for MM, overall survival.

Primary Results:

  • PFS: HR 0.49 (95% CI 0.36–0.67).
  • Overall survival: HR 0.52 (95% CI 0.27–0.98); 5-year OS 93.0% vs 86.9%; deaths 15 (7.7%) vs 26 (13.3%).
  • PFS on first-line treatment for MM: HR 0.58 (95% CI 0.35–0.96).
  • Subgroup highlight: retrospective Mayo 2018 criteria PFS HR 0.36 (95% CI 0.23–0.58).

Source: https://x.com/OncBrothers/status/1866529170832101849

Additional published endpoint (as stated by NEJM):

  • 5-year PFS: 63.1% (daratumumab monotherapy) vs 40.8% (active monitoring).

Source: https://x.com/NEJM/status/1921973720434016868

Safety:

  • Any-grade TEAEs: 96.9% vs 82.7%.
  • Grade 3–4 TEAEs: 40.4% vs 30.1%.
  • Serious TEAEs: 29.0% vs 19.4%.
  • Grade 5 TEAEs: 1.0% vs 2.0%.
  • Treatment discontinuation due to TEAE (daratumumab arm): 11 (5.7%).
  • Selected grade 3–4 TEAEs (≥5%): COVID-19 TEAEs 8.8% vs 5.1%; hypertension 5.7% vs 4.6%.

Source: https://x.com/victorshiyulin/status/1866273872569679896

Key Conclusions:

  • Fixed-duration daratumumab in high-risk smoldering myeloma improved PFS and was associated with improved overall survival versus active monitoring.
  • Safety profile included higher rates of grade 3–4 and serious TEAEs versus active monitoring, with discontinuation due to TEAE reported at 5.7% in the daratumumab arm.

AQUILA Sentiments and Criticisms (Themes)

Theme 1 — Practice-changing framing vs observe-first implementation

  • Rajkumar (practice-changing framing): “Just out: Paradigm changing AQUILA randomized trial…”

Source: https://x.com/VincentRK/status/1866205046855377366

  • Rajkumar (ASH25 observation pathway): “How to follow High Risk Smoldering Myeloma: Observation…”

Source: https://x.com/VincentRK/status/1993402192103956908

  • Chakraborty (observe-first stance): “...but I would still do active surveillance. Reassuring to see that almost no morbid progressions in either arm.”

Source: https://x.com/rajshekharucms/status/1866277618653581388

Theme 2 — OS signal interpretation and control-arm subsequent therapy

  • Prasad (multiplicity concern): “OS doesn't report how it adjust for multiple looks…”

Source: https://x.com/VPrasadMDMPH/status/1866216887597883579

  • Goodman (post-progression CD38 exposure question): “How many patients in control got Daratumumab on progression”

Source: https://x.com/AaronGoodman33/status/1865044832928043469

  • Chakraborty (modern-era regimen critique): “...~30% of patients received a clearly suboptimal 1st line… which makes the OS signal unreliable…”

Source: https://x.com/rajshekharucms/status/1866205353408659948

Theme 3 — Risk definition, SLiM events, and overtreatment risk

  • Rajkumar (ODAC/overtreatment): “I’m not one who likes over treating…”

Source: https://x.com/VincentRK/status/1924950447217090582

  • Chakraborty (SLiM event relevance evolving): “...risk of progression to CRAB myeloma is much lower…”

Source: https://x.com/rajshekharucms/status/1924916232295190619

  • Chakraborty (overtreatment framing): “~40% of patients in the control arm… did not require start… at 5 years!”

Source: https://x.com/rajshekharucms/status/1990126470841164022

Theme 4 — Imaging sensitivity and baseline diagnostic purity

  • Lentzsch: “...interesting to see the HR if pt would have received DWI-WBMRI to exclude active MM”

Source: https://x.com/SLentzsch/status/1866205992498913281

  • Chakraborty (protocol detail): “As per protocol, MRI spine/pelvis was performed at baseline (not WB DW-MRI).”

Source: https://x.com/rajshekharucms/status/1866206213685567724

Theme 5 — Safety burden and fixed-duration tradeoffs

  • Rajkumar: “There is a 10% absolute higher risk of grade 3-4 AEs… related to longer period on study…”

Source: https://x.com/VincentRK/status/1866205079893942357

AQUILA Temporal Sentiment Arc

ASH 2024: primary analysis release and immediate positioning

2025: publication and regulatory/practice integration

ASH 2025 cycle: risk stratification and “treat vs observe” implementation

AQUILA Professional Resources