Employing Chimeric Antigen Receptor (CAR) T-cell Therapy in a Case of Relapsed Multiple Myeloma with Dialysis-Dependent End Stage Renal Disease
Introduction/Background/Significance: Few studies have assessed the outcomes of CAR T-cell therapy in patients with end-stage renal disease (ESRD). Data remain especially limited in the context of relapsed/refractory multiple myeloma (R/R MM), where patients with ESRD were excluded from the KaRMMa and CARTITUDE trials that led to the approval of idecabtagene vicleucel and ciltacabtagene autocleucel (cilta-cel), respectively. Here, we report treatment with cilta-cel for R/R MM and concurrent ESRD requiring peritoneal dialysis (PD).
Materials and Methods/Case Presentation/Objective: A 51-year-old male, diagnosed seven years prior with IgA lambda multiple myeloma after presenting with acute kidney injury (resulting in PD-dependence), anemia, and lytic bone disease, re-presented with relapsed triple-class refractory disease. Given his relapsed disease, he subsequently received cilta-cel.
In preparation for CAR T-cell therapy, the patient underwent a modified lymphodepletion (LD) protocol, receiving cyclophosphamide 300 mg/m2 (standard dose) and fludarabine 15 mg/m2 (50% dose reduction) on days -5, -4, and -3. With assistance from nephrology, the patient continued his home continuous cycling PD regimen from admission to discharge. Leading up to cilta-cel administration, the patient experienced mild electrolyte derangements, including an elevated potassium (up to 5.4 mg/dL) and phosphorous (up to 9.0 mg/dL), which were managed with potassium and phosphate binders, respectively. The number of nightly PD cycles was also increased to improve small molecule clearance. On day +7, the patient experienced grade one cytokine release syndrome, which resolved with supportive care. Two months since having received cilta-cel, he has experienced grade three anemia, grade four thrombocytopenia, and grade three neutropenia, but no neurotoxicity, delayed motor-neurotoxicity, or clinically significant infections. A restaging bone marrow biopsy showed no evidence of disease, and the patient's myeloma markers have significantly decreased, suggesting an early clinical response.
Results/Description/Main Outcome Measures: To our knowledge, this is the first known report of using cilta-cel therapy in a patient undergoing PD. A major concern for CAR T-cell therapy in the setting of renal replacement therapy is the potential for increased toxicity secondary to LD therapy, especially due to fludarabine, which is renally cleared. Within the limited literature on this topic, there has been great variability in the choice of CAR T-cell therapy LD regimens (as some have omitted fludarabine completely while others preferred dose-reduction).1 Furthermore, it remains unclear as to how to best coordinate the timing between dialysis and LD. LD was most commonly given 12 hours after dialysis in those receiving intermittent hemodialysis.1 However, in this case, given the steadier drug metabolism associated with PD, timing between LD and dialysis was deemed less critical. Our patient did not experience any increased toxicity.
Conclusions: We demonstrate that dialysis-dependent ESRD should not necessarily be a comorbidity that prevents feasibly administering CAR T-cell therapy at a major academic center. Nevertheless, further studies are warranted to determine how LD and dialysis regimens can be better standardized to ensure maximal safety and efficacy of CAR T-cell products in this patient population.
References
1. Pak WLW, et al. CAR T-Cell Therapy Use in Patients with Multiple Myeloma and Kidney Failure on Maintenance Hemodialysis: A Report of 2 Cases. Kidney Med. 2024 Jun 14;6(8):100856.
