ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: TH-PO0164

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

Session Information

Category: Onconephrology

  • 1700 Onconephrology

Authors

  • Swamy, Varsha, The University of Chicago, Chicago, Illinois, United States
  • Kelly, Kaitlin, The University of Chicago, Chicago, Illinois, United States
  • Koyner, Jay L., The University of Chicago, Chicago, Illinois, United States
  • Derman, Benjamin A, The University of Chicago, Chicago, Illinois, United States
  • Bonilla, Marco, The University of Chicago, Chicago, Illinois, United States
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.

PatientDiagnosisLymphodepletionDialysisComplicationsOutcome
53 Fλ light chain plasmablastic myelomaCYC 300 mg/m2 + fludarabine 20 mg/m2 on days -5, -4, -312 hours post fludarabine Grade 2 CRS
Grade 2 ICANS
Thrombocytopenia
IEC-HS
Persistent extramedullary disease +60 days
Expired day +293
79 Mλ light chain MMCYC 300 mg/m2 + fludarabine 20 mg/m2 on days -5, -4, -312 hours post fludarabine Neutropenic fever
Grade 1 CRS
Complete response +60 days
72 FIgA λ light chain MMBendamustine 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 CRSComplete response +60 days Progression of disease +120 days Expired +274 days
61 Fλ light chain MMCYC 300 mg/m2 + fludarabine 15 mg/m2 on days -5, -4, -312 hours post fludarabine Grade 1 CRS
IEC-HS
Partial response +30 days
No evidence of disease at +60 days
69 FΚ light chain MMCYC 300 mg/m2 + fludarabine 15 mg/m2 on days -6, -5, -312 hours post fludarabineNeutropenic fever
Grade 1 CRS
IEC-HS
Anemia
Evidence of extramedullary disease +99 days

Digital Object Identifier (DOI)