The International Myeloma Working Group (IMWG), in a new guideline, is recommending that patients with multiple myeloma (MM) undergo a series of tests to evaluate renal impairment (RI). The guidance, which also recommends cut-off points for certain tests, appears in the Journal of Clinical Oncology.
RI in patients with MM is caused mainly by the toxic effects of the monoclonal light chains on basement membranes of the glomeruli and/or the renal tubule,” the authors explained. Cast nephropathy (CN), a condition that often causes acute injury to the kidneys, is often seen in MM patients. The working group’s recommendations offer practical advice for managing and diagnosing patients with this condition.
“Acute RI is a myeloma emergency. Diagnosis should be established as fast as possible, and antimyeloma therapy should be started immediately after confirmation of diagnosis to rapidly restore renal function,” according to the IMWG.
Investigators analyzed recent studies that addressed the management of MM patients with RI, and used the Grading of Recommendation, Assessment, Development, and Evaluation Working Group system to formulate this guidance.
In a grade A recommendation, they suggested MM patients at the time of diagnosis and disease assessment undergo the following tests: serum creatinine, estimated glomerular filtration rate (eGFR), electrolytes measurements, free light chain (if it’s available) and urine electrophoresis of a sample that’s collected over a 24-hour period.
To evaluate patients with stabilized serum creatinine (sCr), clinicians could use either the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or the Modification of Diet in Renal Disease (MDRD) formula for eGFR. The working group’s authors noted that they preferred CKD-EPI over MDRD, because it’s more accurate in reflecting GFR levels, particularly high levels.
If a patient has nonselective proteinuria or significant albuminuria or relatively low free light chains (FLCs) < 500 mg/L, clinicians should look for evidence of amyloidosis or comorbid conditions like monoclonal immunoglobulin deposition disease. “In cases in which amyloidosis is suspected, a subcutaneous fat aspirate may reveal the diagnosis in approximately 70% of patients; if the fat biopsy is negative, a renal biopsy is required,” the working group recommended.
Renal biopsies are not required when a patient has proteinuria with high FLCs > 500–1,500 mg/L. However, a biopsy could prove useful in patients who have other conditions, like chronic hypertension or diabetes.
The working group also set criteria or cut-off points for renal response to antimyeloma therapy. As an example, for complete renal response, the baseline eGFR (mL/min/1.73 m2) would be <50 and the best creatinine clearance (CrCl) response would be ≥60 mL/min. For partial response, the baseline eGFR would be <15 and the best CrCl response would be 30-59 mL/min.
For minor renal response, baseline eGFR would be <15 and the best CrCl response would be 15-29 mL/min.
In another important recommendation, the working group stressed that bortezomib should remain a frontline care method for managing MM patients with related RI. Administration of this proteasome inhibitor should take place over a 3-week cycle, starting at a dosage of 1.3 mg/m2 on days 1, 4, 8, and 11, the working group indicated.