eGFR Discordance in Patients with Multiple Myeloma Treated with Chimeric Antigen Receptor T Cell and Autologous Stem Cell Therapies: A Retrospective Analysis

Background: Chimeric antigen receptor T-cell therapy and autologous stem cell therapy are used in hematologic malignancies such as multiple myeloma. Typical preconditioning chemotherapy includes Fludarabine/Cytoxan for CAR-T, and Melphalan for ASCT. We conducted a retrospective study to evaluate the serum Cystatin C CKD-EPI eGFR equation, in comparison to sCr, and link dosing regimens to patient-centered outcomes such as chemotherapy-related toxicity and hospitalization. Methods: In this cohort of multiple myeloma patients, we examined 37 who received CAR-T therapy and 76 who received ASCT 2021-2025. Melphalan/Fludarabine dosing was based on pre-transplant eGFR calculated from sCr and Cystatin C. Discordant patients were those with discordance between sCr and Cystatin C based eGFRs that led to a discrepancy in their conditioning chemotherapy dosing, and concordant patients as those without. The dosing thresholds for Fludarabine were a full 30 mg dose in those with an eGFR >60 mL/min, 20% reduction in 30-59 mL/min, and a 50% reduction in <30 mL/min. With Melphalan, the eGFR threshold was 50 mL/min, below which the dose was reduced from the standard 200 mg to 140 mg. The primary outcome was incidence of Melphalan/Fludarabine toxicity, defined as exceeding the therapeutic dose due to eGFR discrepancies and hospitalization within 30 days. Results: With 16 CAR-T and 9 ASCT patients excluded due to missing data, we found a significant difference between a median SCr eGFR of 93 mL/min and a median Cystatin C eGFR of 79 mL/min (p=0.0096, n=97). 7 CAR-T patients had discordant eGFRs resulting in a different Fludarabine dosing and 24 ASCT patients had discordant eGFRs resulting in a higher Melphalan dosing. Within 30 days of treatment, 60% of concordant and 100% of discordant ASCT patients were hospitalized. There was a 100% hospitalization rate in concordant and discordant CAR-T patients. Median hospitalization duration was 2 days in concordant versus 7 in discordant in ASCT patients, and 7 days in concordant versus 9 in discordant CAR-T patients. Conclusion: Using Cystatin C instead of sCr could significantly decrease the incidence of Melphalan or Fludarabine overdose, potentially preventing hospitalization and reducing treatment-related toxicity. Further prospective studies are warranted to confirm these findings in multiple myeloma patients.