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Updated: Mar 1, 2026
An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Discrepancy in Estimating GFR for Melphalan Dosing in Multiple Myeloma Patients Undergoing Autologous Stem Cell
Benjamin Teruel1, Ashley L Golbus1, Elaine Park1
1Department of Medicine, Medical University of South Carolina, Charleston, SC, USA.
Key Points:
Accurate GFR assessment is critical to guiding dosing of cancer therapy and minimizing the risks of toxicity and undertreatment. The role of cystatin C for estimating eGFR for melphalan dosing for multiple myeloma patients undergoing autologous stem cell transplant is poorly investigated. eGFR based on serum creatinine may overestimate melphalan dosing resulting in toxicity in one in five patients undergoing autologous stem cell transplant.
Background:
Accurate renal dosing of high-dose melphalan as conditioning chemotherapy is critical for patients with multiple myeloma (MM) undergoing autologous stem cell transplant (ASCT). In clinical practice, serum creatinine (sCr) is used to eGFR for dosing calculations. The objective of our study was to compare sCr-based eGFR to serum cystatin C-based eGFR (eGFRcys) for melphalan dosing in patients undergoing ASCT for MM to determine discrepancies in dosing and the effect on patient centered outcomes including chemotherapy-related toxicity and hospitalization and to assess International Myeloma Working Group response criteria at 3 and 12 months.
Methods:
We conducted a retrospective study including 76 patients with MM who received melphalan conditioning before ASCT. Melphalan dosing in all patients was based on pretransplant eGFR calculated from sCr (200 mg/m 2 for eGFR >50 ml/min, 140 mg/m 2 for eGFR <50 ml/min). We calculated eGFR using both sCr and cystatin C levels before transplantation and observed the 30-day hospitalization from symptoms of melphalan toxicity. We identified a discordant patient group, whose cystatin C eGFR was calculated <50 ml/min compared with sCr eGFR >50 ml/min and would have qualified for a reduced melphalan dose.
Results:
Of 76 patients, 13 (17%) were identified as having received a higher than intended dose of melphalan when eGFR was estimated using sCr rather than cystatin C (200 mg/m 2 rather than 140 mg/m 2 , discordant dosing). One hundred percent of discordant patients were hospitalized within 30 days of melphalan dosing compared with 60% of the concordant patients whose eGFR was >50 ml/min with both cystatin C and sCr-based eGFR, with melphalan dosing 200 mg/m 2 ( P = 0.006). Furthermore, patients with discordant dosing had a significantly longer hospitalization duration of 7 days compared with 2.5 days in patients with concordant dosing ( P = 0.0014). More patients qualified for dose reduction using eGFRcys compared with combined sCr-cystatin C-based eGFR ( P = 0.02).
Conclusions:
Discordance between creatinine and eGFRcys calculations in ASCT patients was linked to inconsistent melphalan dosing and associated with an increase in adverse outcomes.
