Acute Kidney Injury, Light Chain Nephropathy, Multiple Myeloma
Conditions
Brief summary
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.
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.
Interventions
PROCEDUREPlasma 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
DRUGDaratumumab
Patients treated with daratumumab within 30 days of diagnosis of light chain cast nephropathy
Sponsors
Brigham and Women's Hospital
Janssen, LP
Baystate Health
Boston Medical Center
Dana-Farber Cancer Institute
Massachusetts General Hospital
Mayo Clinic
M.D. Anderson Cancer Center
Medical University of South Carolina
H. Lee Moffitt Cancer Center and Research Institute
Icahn School of Medicine at Mount Sinai
Northwell Health
Ochsner Health System
Ohio State University
Stanford University
Texas Medical Center
Thomas Jefferson University
University of Alabama at Birmingham
University of California, Los Angeles
University of Chicago
University of Colorado Health
University of Minnesota
University of New Mexico
University of Pennsylvania
University of Pittsburgh
University of Virginia
University of Washington
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The primary composite outcome is the rate of survival with renal recovery within 90 days from the diagnosis of light chain cast nephropathy. | 90 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The proportion of patients with Receipt of RRT within 30 days, 60 days, and 90 days following diagnosis of light chain cast nephropathy | 30, 60, 90 days | The proportion of patients with Receipt of RRT within 30 days, 60 days, and 90 days following diagnsosis of LCCN |
| The proportion of patients with Progressive AKI | 30, 60, 90 days | 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. |
| Survival to hospital discharge | 30 days | Survival to hospital discharge and KRT-independent among patients admitted within 30 days of the diagnosis of light chain cast nephropathy. |
| Renal function (SCr) at hospital discharge | 30 days | 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 |
| Time to first renal recovery | 180 days | 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 |
| Kidney recovery | 30 (+/-15), 60 (+/-15), 90 (+/-30) days, and 180 days (+/-60 days) | 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. |
| 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. | 90, 180, 360 days | At day 90, 180, 360, with day 0 defined as date of LCCN diagnosis |
| Adverse events | 60 days | Infection, re-hospitalization, transfusion reactions, bleeding diatheses. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORShruti Gupta, MD
Brigham and Women's Hospital
Outcome results
None listed