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Clinically-suspected cast nephropathy: A retrospective, national, real-world study
Agoston G Szabo1,2, Jonathan Thorsen1,3, Katrine F Iversen1,2
1Department of Hematology, Vejle Hospital, Vejle and University of Southern Denmark, Vejle, Denmark.
Insights
Multiple myeloma patients with cast nephropathy (CN) face a high risk of death and kidney failure. Early, deep hematologic response is critical for improving survival in these critically ill patients.
Area of Science:
- Nephrology
- Hematology
- Oncology
Background:
- Multiple myeloma (MM) patients with cast nephropathy (CN) experience severe acute kidney injury, leading to high rates of dialysis-dependent renal failure and mortality.
- Clinical trials often exclude patients with severe renal insufficiency, necessitating real-world data to understand CN outcomes.
- Cast nephropathy represents a significant clinical emergency in multiple myeloma management.
Purpose of the Study:
- To assess the outcomes of multiple myeloma patients presenting with clinically-suspected cast nephropathy using real-world data.
- To identify factors associated with survival and renal recovery in this high-risk patient group.
- To evaluate the effectiveness of current treatment standards for multiple myeloma with cast nephropathy.
Main Methods:
- Analysis of 2252 patients from the Danish Multiple Myeloma Registry (2013-2017).
- Identification of 204 patients with clinically-suspected CN (serum creatinine >177 μmol/L and serum free light chain >1000 mg/L).
- Assessment of treatment initiation (bortezomib-based therapy in 94%) and patient outcomes, including mortality and renal recovery.
Main Results:
- 31% of patients presented with dialysis-dependent renal failure; 33% died within the first year.
- Kidney biopsies confirmed CN in 74% of cases where performed.
- Patients with clinically-suspected CN had worse overall survival (OS) compared to other symptomatic MM patients.
- Renal recovery correlated with significant reductions in involved serum free light chains (sFLC).
- Achieving very good partial response or better, and/or deep sFLC reduction at 3 months, predicted superior OS.
Conclusions:
- Multiple myeloma patients with clinically-suspected cast nephropathy exhibit alarmingly high one-year mortality despite current standards of care.
- Early and profound hematologic response is crucial for improving survival in these patients.
- Real-world data highlight the urgent need for improved therapeutic strategies for cast nephropathy in multiple myeloma.
Abstract:
Presentation with severe acute kidney injury due to cast nephropathy (CN) is a medical emergency in multiple myeloma (MM), with high risk of dialysis-dependent renal failure and death. Accrual of patients with CN into interventional studies is difficult, while phase III trials exclude patients with severe renal insufficiency. Real-world data are warranted. We assessed 2252 patients from the population-based Danish Multiple Myeloma Registry (DMMR) who were diagnosed between 2013 and 2017. We identified 204 patients with clinically-suspected CN, defined as serum creatinine concentration >177 μmol/L and serum free light chain (sFLC) concentration >1000 mg/L at the time of diagnosis. The median age was 72 years. Thirty-one percent of patients presented with dialysis-dependent renal failure. Kidney biopsies were performed in 19% of patients and showed CN in 74% of cases. Despite prompt initiation of bortezomib-based therapy in 94% of patients, 33% of patients died in the first year after diagnosis. Compared with the rest of the patients in the DMMR with symptomatic MM, patients with clinically-suspected CN had worse overall survival (OS) irrespective of transplant eligibility. Achievement of renal recovery was associated with deep reductions of involved sFLC. Achievement of very good partial response or better in the first line of therapy and/or deep reduction of involved sFLC at 3 months after initiation of therapy were associated with superior OS. In conclusion, MM patients presenting with clinically-suspected CN have an alarmingly high one-year mortality when treated with current standards of care. Early and deep hematologic response is crucial for survival.
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