Cystatin C as a Superior Biomarker for Melphalan Dosing in Patients with Multiple Myeloma Undergoing Autologous Stem-Cell Transplant: A Single-Center Retrospective Analysis

Background: Accurate dosing of melphalan is critical for patients with multiple myeloma undergoing autologous stem cell transplant (ASCT). Traditionally, serum creatinine (SCr) is used to estimate glomerular filtration rate (GFR) for melphalan dosing calculations. This study seeks to evaluate the effectiveness of Cystatin C in predicting appropriate melphalan induction doses compared to SCr in patients with multiple myeloma undergoing ASCT. Methods: A retrospective cohort study was conducted on 76 patients diagnosed with multiple myeloma who received melphalan conditioning before ASCT. Melphalan dosing in all patients was based on pre-transplant eGFR calculated from SCr. This dosing is 200 mg for eGFR >50 mL/min/1.73m2, 140 mg for eGFR <50. Patient GFR was estimated using Cystatin C levels immediately prior to transplantation. The primary outcome was the incidence of melphalan overdosing, defined as those cases that exceeded the therapeutic dose, due to GFR estimation discrepancies between the two biomarkers and the presence of a hospitalization related to melphalan toxicity within 30 days of Melphalan therapy. Results: Of the 76 patients, 11 (14.5%) were identified as having received a higher dose of melphalan than anticipated when GFR was estimated using SCr compared to Cystatin C. These patients exhibited higher incidences of treatment-related toxicity due to diarrhea, mucositis, and/or fever and resulted in hospitalization in 100% of patients with melphalan overdose. Of note, 23 patients (35%) of patients with appropriate melphalan dosing as per SCr eGFR and Cystatin C eGFR did not experience toxicity (p = 0.01). Conclusion: While melphalan is associated with a high baseline toxicity, use of Cystatin C in place of SCr to estimate GFR could significantly decrease the incidence of melphalan toxicity. Further prospective studies are warranted.