Biomarkers of AKI in Patients Receiving Daratumumab

Biomarkers of AKI in Patients With Multiple Myeloma Receiving Daratumumab: A Pilot Study

The goal of this prospective observational study is to understand changes in urinary and blood biomarkers associated with acute kidney injury (AKI) in patients newly diagnosed with multiple myeloma and being treated with Daratumumab SC. The aims of the study are:

To measure changes in plasma and urinary biomarkers of AKI before initiation of Daratumumab therapy and 30 days after initiation of therapy.

To establish whether these biomarkers serve to aid in early detection and prevention of AKI

Participants will give urine and blood samples at their normally scheduled lab appointments.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma; Acute Kidney Injury; Light Chain Nephropathy
• Intervention / Treatment: Drug: Daratumumab

Detailed Description

Serum creatinine is an insensitive marker of AKI, often rising late and after significant injury has already occurred. A number of novel markers have recently been shown to have utility in the early detection of AKI. These markers have shown promise in preclinical and human studies in multiple other clinical settings (e.g., cardiac surgery, coronary angiography, critical illness), but have not been studied in the context of multiple myeloma. Specifically, elevated pre-procedural plasma levels of soluble urokinase-type plasminogen activator receptor (suPAR), the circulating form of a membrane-bound protein expressed by immunologically active cells, have been demonstrated to be predictive of AKI patients undergoing coronary angiography, cardiac surgery, and in critically ill patients (Hayek et al., NEJM, 2020), and levels rise early after injury. Similarly, urinary levels of Dickkoph-3 (DKK3), a stress-induced tubular epithelia-derived glycoprotein, have been demonstrated to predict AKI after cardiac surgery and following administration of iodinated contrast (Schunk et al., Lancet, 2019).

The aim of this study is to conduct a pilot, prospective, non-interventional study testing changes in novel plasma and urinary biomarkers of kidney injury in patients with newly-diagnosed multiple myeloma treated with daratumumab who are at risk for AKI.

The hypothesis is that patients with multiple myeloma and at risk for developing AKI, but without AKI at baseline, will have at least a 10% decline in plasma soluble urokinase-type plasminogen activator receptor and urinary levels of Dickkoph-3 following treatment with daratumumab.

The primary outcome(s) will be changes in plasma suPAR and urinary levels of DKK3 between treatment initiation of daratumumab (day 0, or up to 7 days prior) and day +30 (+/-7 days) from the time of treatment initiation.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with multiple myeloma

Description

Inclusion Criteria:

• Patients must be ≥ 18 years of age
• Patients can be on a clinical trial

• Patients must have had a confirmed new diagnosis of MM following revised IMWG criteria

  1. New diagnosis of systemic multiple myeloma defined as no documented history of prior multiple myeloma.
  2. Further, no prior systemic treatment with anti-myeloma agent is permitted with the exception of corticosteroids for no more than 4 weeks.
  3. Prior history of receiving radiation therapy for the treatment of plasmacytoma or lytic lesions, is permitted on the study.
• Patients receiving SC daratumumab
• Patients must be able to sign the informed consent
• Patients must be at risk for AKI and meet at least two of the three following criteria: age ≥65; baseline eGFR <60; or use of NSAIDs (not including aspirin), bisphosphonates, intravenous contrast, diuretics, or RAS inhibitors in the 14 days preceding treatment initiation

Exclusion Criteria:

• End stage renal disease (e.g, on long-term dialysis or with a kidney transplant and on long-term dialysis) at the time of starting daratumumab
• Acute kidney injury defined as a ≥1.5-fold rise in baseline SCr, where baseline SCr is the lowest SCr in the 365 days preceding receipt of daratumumab, or with AKI on RRT
• Previous exposure to daratumumab or other anti-CD38 therapy
• Patients receiving intravenous daratumumab
• Exposure to concomitant chemotherapy which could be perceived as nephrotoxic within 30 days of receipt of daratumumab (e.g., cisplatin, mTOR inhibitors)
• Moribund patients (e.g., those expected to die in the next 30 days from the time of screening)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with multiple myeloma; Patients with multiple myeloma being newly initiated on daratumumab	Drug: Daratumumab; Daratumumab is not being administered as part of the study. Patients will receive daratumumab as part of their clinical care, and blood and urine will be collected in order to measure biomarkers pre- and post-daratumumab administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma and Urine Biomarkers	The primary outcome(s) will be changes in plasma suPAR and urinary levels of DKK3 between treatment initiation of daratumumab (day 0, or up to 7 days prior) and day +30 (+/-7 days) from the time of treatment initiation.	30 days

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Janssen Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2024
• Primary Completion (Actual): January 15, 2026
• Study Completion (Actual): January 15, 2026

Study Registration Dates

• First Submitted: August 8, 2024
• First Submitted That Met QC Criteria: August 8, 2024
• First Posted (Actual): August 12, 2024

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 25, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Renal Insufficiency; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Acute Kidney Injury; Multiple Myeloma; Antineoplastic Agents; daratumumab
• Other Study ID Numbers: 23-270

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No