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AQUILA

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. Vincent Rajkumar and 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