Chimeric Antigen Receptor T Cell (CAR-T) Therapy in Dialysis-Dependent Patients with Multiple Myeloma

Introduction: The indications for CAR-T as an effective treatment for patients with Multiple Myeloma (MM) continue to expand. However, there is limited data on the safety and efficacy of CAR-T in advanced CKD or dialysis-dependence. Concerns regarding CAR-T therapy in these patients include potential for excess toxicity from lymphodepleting regimens such as fludarabine and potential for higher incidence/grade of toxicities from CAR-T therapy such as cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), and immune effector cell-associated hemophagocytic-like syndrome (IEC-HS). Case Description: We present a case series of dialysis-dependent patients who underwent treatment with CAR-T (Ciltacabtagene autoleucel) therapy, including 4 on hemodialysis (HD) and 1 on peritoneal dialysis (PD). Discussion: Ciltacabtagene autoleucel can be safely and effectively administered in patients on HD or PD with refractory/relapsed MM with a dose-adjusted lymphodepleting regimen and tailored dialysis schedules and prescriptions. All patients experienced grade 1-2 CRS, 1 experienced ICANS, and 3 experienced IEC-HS. This may be because ESKD in the setting of myeloma therapy may be associated with more aggressive disease biology, which may lead to higher grade toxicities from CAR-T therapy. It is unclear if the reduced-dose fludarabine/cyclophosphamide (CYC) or bendamustine lymphodepletion strategy impacted outcomes. The overall response rate was 100%. At least one patient had response beyond one year of therapy, with another patient in ongoing response. The short responses among the other three patients may be attributed to the aggressive disease features, including high-risk cytogenetic abnormalities (100%), plasmablastic features (40%), and/or extramedullary disease (60%), which are known to be associated with poorer outcomes with CAR-T. Standardized protocols to further clarify optimal dosing of lymphodepleting chemotherapy and CAR-T products along with assessment of long-term outcomes in patients with ESKD are needed. - Patient Diagnosis Lymphodepletion Dialysis Complications Outcome 53 F λ light chain plasmablastic myeloma CYC 300 mg/m2 + fludarabine 20 mg/m2 on days -5, -4, -3 12 hours post fludarabine Grade 2 CRSGrade 2 ICANSThrombocytopenia IEC-HS Persistent extramedullary disease +60 daysExpired day +293 79 M λ light chain MM CYC 300 mg/m2 + fludarabine 20 mg/m2 on days -5, -4, -3 12 hours post fludarabine Neutropenic feverGrade 1 CRS Complete response +60 days 72 F IgA λ light chain MM Bendamustine 70 mg/m2 on day -6, -5 8 hour session of PD on day -6 (4 hours post dose), day -5 (7 hours post dose) Grade 1 CRS Complete response +60 days Progression of disease +120 days Expired +274 days 61 F λ light chain MM CYC 300 mg/m2 + fludarabine 15 mg/m2 on days -5, -4, -3 12 hours post fludarabine Grade 1 CRSIEC-HS Partial response +30 days No evidence of disease at +60 days 69 F Κ light chain MM CYC 300 mg/m2 + fludarabine 15 mg/m2 on days -6, -5, -3 12 hours post fludarabine Neutropenic feverGrade 1 CRSIEC-HS Anemia Evidence of extramedullary disease +99 days