Outcomes of CD19-Targeted Chimeric Antigen Receptor T Cell Therapy for Patients with Reduced Renal Function Including...

Area of Science:

• Hematology-Oncology
• Nephrology
• Immunotherapy

Background:

• Patients with renal impairment (RI) are often excluded from clinical trials of chimeric antigen receptor (CAR) T cell therapies.
• Relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) is a challenging indication for CAR T cell therapy.
• The impact of baseline renal function on CAR T cell therapy outcomes is not well-established.

Purpose of the Study:

• To evaluate the safety and efficacy of standard of care (SOC) CAR T cell therapy in patients with R/R DLBCL and varying degrees of renal impairment.
• To compare renal and survival outcomes based on baseline RI status and fludarabine dose reduction.
• To identify factors associated with acute kidney injury (AKI) and its impact on clinical outcomes.

Main Methods:

• Retrospective, single-center cohort study of 166 patients with R/R DLBCL treated with axicabtagene ciloleucel or tisagenlecleucel.
• Renal impairment defined as estimated glomerular filtration rate <60 mL/min/1.73 m²; AKI graded using Kidney Disease: Improving Global Outcomes criteria.
• Comparison of outcomes between patients with and without baseline RI, and with standard-dose versus reduced-dose fludarabine.

Main Results:

• 10.2% of patients had baseline RI; incidence of any grade AKI (42% vs 21%) and severe AKI (5.8% vs 7.3%) was not significantly different between RI and non-RI groups.
• Decreased renal perfusion (72%) and cytokine release syndrome (CRS) (44%) were common causes of AKI.
• Progression-free survival (PFS) and overall survival (OS) did not differ based on baseline RI or fludarabine dose.
• Patients who developed AKI had significantly worse PFS (HR, 2.1) and OS (HR, 3.9) compared to those without AKI.
• Higher peak inflammatory cytokine levels were observed in patients who experienced AKI.
• Two patients with end-stage renal disease (ESRD) on dialysis received CAR T cell therapy with careful lymphodepletion planning.

Conclusions:

• Baseline renal function does not significantly impact renal or efficacy outcomes following CAR T cell therapy in DLBCL.
• Acute kidney injury (AKI), often associated with CRS and high cytokine levels, is a significant predictor of worse clinical outcomes.
• CAR T cell therapy is feasible in patients with ESRD, necessitating meticulous lymphodepletion strategies.