Novel Treatments in Improving Renal Outcomes in Light Chain Cast Nephropathy

The Effect of Novel Treatments in Improving Renal Outcomes Among Patients With Light Chain Cast Nephropathy

Objective 1: To test whether treatment with plasma exchange improves renal recovery in patients with light chain cast nephropathy Objective 2: To compare renal outcomes among patients treated with plasma exchange versus daratumumab-based regimens versus non-daratumumab based-regimens.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma; Acute Kidney Injury; Light Chain Nephropathy
• Intervention / Treatment: Procedure: Plasma exchange; Drug: Daratumumab

Detailed Description

Objective 1:

We will collect data from patients treated with plasma exchange from major centers across the United States to investigate whether plasma exchange improves renal outcomes.

Specifically, we will collect data on at least 150 patients treated with plasma exchange along with 300 control patients not treated with plasma exchange.

Objective 2:

We will compare renal outcomes among patients with light chain cast nephropathy and AKI treated with plasma exchange (n=150) versus daratumumab based regimen (eg Dara-CyborD) (n=150) versus other novel regimens (e.g., CyborD or another non-daratumumab-based regimen) (n=150). We will examine whether patients who receive dara-based regimens are more likely to have renal recovery compared to patients who do not receive dara-based regimens and to patients who receive plasma exchange. Given the infrequency with which plasma exchange is performed on a single-center level, we will compare outcomes among patients treated with plasma exchange, utilizing data from the multicenter study to those patients who were treated with daratumumab-based regimens without plasma exchange versus non- daratumumab-based regimen.

• Study Type: Observational
• Enrollment (Estimated): 450

Contacts and Locations

• Study Contact: Name: Shruti Gupta, MD; Phone Number: 5712366626; Email: sgupta21@bwh.harvard.edu
• Study Contact Backup: Name: Christina Shincovich, MD; Email: cshincovich@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02130
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Shruti Gupta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with multiple myeloma and clinically-suspected or biopsy-proven light chain cast nephropathy

Description

Inclusion Criteria for Plasma Exchange-Treated Patients:

1. Adult (≥18 years old)
2. Either a new diagnosis of multiple myeloma confirmed by bone marrow plasmayctosis >10% or acute relapse of multiple myeloma
3. Light chain cast nephropathy, with involved light chain >500 mg/L
4. Acute kidney injury, defined as ≥1.5-fold rise in SCr from baseline (as defined in study outcomes) or the need for renal replacement therapy (RRT).
5. Treated with at least 1 round of plasma exchange within 30 days of diagnosis of cast nephropathy
6. Treated with plasma exchange in 2010 or later

Inclusion Criteria for Control Patients:

1. Adult (≥18 years old)
2. Either a new diagnosis of multiple myeloma confirmed by bone marrow plasmayctosis >10% or acute relapse of multiple myeloma
3. Light chain cast nephropathy, with involved light chain >500 mg/L
4. Acute kidney injury, defined as ≥1.5-fold rise in SCr from baseline or the need for renal replacement therapy (RRT)

Exclusion Criteria for Both Plasma Exchange-Treated Patients and Control Patients:

1. Patients with end stage kidney disease
2. Patients with amyloidosis or monoclonal immunoglobulin deposition disease
3. Patients with chronic lymphocytic leukemia, plasma cell leukemia, or Waldenstrom's
4. Moribund condition (e.g., patients who died within 48 hours of initiation of plasma exchange)
5. Active urinary tract obstruction on renal imaging
6. Patients with significant albuminuria (≥2+ on urinary dipstick or >10% fraction on UPEP)
7. Patients with other biopsy-proven causes of AKI (non-cast nephropathy lesions)
8. Patients who did not receive clone-directed therapy for myeloma
9. Patients who received plasma exchange >30 days from the time of diagnosis of cast nephropathy

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients treated with plasma exchange; Treated with plasma exchange ithin 30 days of diagnosis of light chain cast nephropathy	Procedure: Plasma exchange; Patients treated with plasma exchange within 30 days of diagnosis of light chain cast nephropathy Patients not treated with daratumumab within 30 days of diagnosis of light chain cast nephropathy
Patients not treated with plasma exchange; Patients not treated with plasma exchange within 30 days of diagnosis of light chain cast nephropathy
Patients treated with daratumumab; Patients treated with daratumumab within 30 days of diagnosis of light chain cast nephropathy	Drug: Daratumumab; Patients treated with daratumumab within 30 days of diagnosis of light chain cast nephropathy
Patients not treated with daratumumab; Patients treated with daratumumab within 30 days of diagnosis of light chain cast nephropathy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary composite outcome is the rate of survival with renal recovery within 90 days from the diagnosis of light chain cast nephropathy.	To meet the primary outcome, patients must be alive, not RRT-dependent (e.g., were never on dialysis/no longer on dialysis), and have a decline of at least one stage of AKI severity compared to their highest AKI stage achieved at the time of light chain cast nephropathy-associated AKI. AKI staging will be based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria, where stage 1 is a 1.5-1.9-fold rise in SCr from baseline; stage 2 is a 2-2.9-fold rise from baseline; and stage 3 is a 3-fold rise in SCr from baseline or initiation of RRT. Baseline SCr is defined as the lowest SCr in the 365 days preceding the diagnosis of light chain cast nephropathy.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients with Receipt of RRT within 30 days, 60 days, and 90 days following diagnosis of light chain cast nephropathy	The proportion of patients with Receipt of RRT within 30 days, 60 days, and 90 days following diagnsosis of LCCN	30, 60, 90 days
The proportion of patients with Progressive AKI	Defined as progression from existing AKI (stage 2) to a higher stage (stage 3 or receipt of RRT) within 30, 60, and 90 days following diagnosis of light chain cast nephropathy. AKI staging at each of these time points will be defined based on KDIGO criteria outlined above.	30, 60, 90 days
Survival to hospital discharge	Survival to hospital discharge and KRT-independent among patients admitted within 30 days of the diagnosis of light chain cast nephropathy.	30 days
Renal function (SCr) at hospital discharge	Renal function (SCr) at hospital discharge (% increase compared to baseline) among patients who are admitted within 30 days of their diagnosis of light chain cast nephropathy	30 days
Time to first renal recovery	Renal recovery will be defined as not RRT-dependent, and with nadir SCr returning to <50% of baseline. This will be assessed within 180 days following the diagnosis of light chain cast nephropathy	180 days
Kidney recovery	at 30 (+/-15), 60 (+/-15), 90 (+/-30) days, and 180 days (+/-60 days) following the diagnosis of light chain cast nephropathy, , defined as survival, KRT-independent, and with SCr <1.5-fold baseline at each of the above time points.	30 (+/-15), 60 (+/-15), 90 (+/-30) days, and 180 days (+/-60 days)
Overall survival at day 90, 180, 360, with day 0 defined as date of LCCN diagnosis. Patients who die within 48 hours of the diagnosis will be excluded.	At day 90, 180, 360, with day 0 defined as date of LCCN diagnosis	90, 180, 360 days
Adverse events	Infection, re-hospitalization, transfusion reactions, bleeding diatheses.	60 days

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Medical University of South Carolina; M.D. Anderson Cancer Center; Massachusetts General Hospital; Mayo Clinic; University of Pennsylvania; University of California, Los Angeles; Northwell Health; Dana-Farber Cancer Institute; University of Alabama at Birmingham; University of Chicago; Icahn School of Medicine at Mount Sinai; University of Pittsburgh; Boston Medical Center; University of Washington; Stanford University; Ohio State University; University of Minnesota; University of Virginia; Thomas Jefferson University; H. Lee Moffitt Cancer Center and Research Institute; University of New Mexico; Janssen, LP; Ochsner Health System; Baystate Health; University of Colorado Health; Texas Medical Center
• Investigators: Principal Investigator: Shruti Gupta, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: June 26, 2024
• First Submitted That Met QC Criteria: July 1, 2024
• First Posted (Actual): July 3, 2024

Study Record Updates

• Last Update Posted (Actual): November 19, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

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; Therapeutics; Surgical Procedures, Operative; Biological Therapy; Blood Component Removal; Blood Transfusion; Plasmapheresis; Sorption Detoxification; Extracorporeal Circulation; daratumumab; Plasma Exchange
• Other Study ID Numbers: 2021P002205

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: Yes