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Outcomes of CD19 targeted CAR T-cell Therapy for Patients with Reduced Renal Function Including ....

Transplantation and Cellular Therapy

Anthony C. Wood Ariel Perez Perez Brian Arciola Kedar Patel Grace Johnson Elizabeth DiMaggio Christina A Bachmeier Kayla Reid Salvatore Carallo Melanie H. Vargas Rawan Faramand Julio C. Chavez Bijal Shah Sameh Gaballa Farhad Khimani Hany Elmariah Taiga Nishihori Aleksandr Lazaryan Ciara Freeman Marco L. Davila Frederick L. Locke Rahul Mhaskar Claude Bassil Michael D. Jain


Background Patients with renal impairment (RI) are typically excluded from trials evaluating chimeric antigen receptor (CAR) T-cell therapies. We evaluated the outcomes of patients with RI receiving standard-of-care (SOC) CAR T-cell therapy for relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL).

Patients and Methods This was a retrospective, single-center cohort study of R/R DLBCL patients treated with SOC axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) after 2 or more prior lines of therapy. Renal and survival outcomes were compared based on RI and fludarabine (flu) dose-reduction (DR) status. RI was defined by an estimated glomerular filtration rate of <60 mL/min/1.73 m2 as determined by the Modification of Diet in Renal Disease equation using day -5 creatinine (Cr) values. Acute kidney injury (AKI) was identified and graded using standard Kidney Disease: Improving Global Outcomes criteria. Renal recovery occurred if Cr was within 0.2 mg/mL of baseline by day +30. Flu was considered DR if given at <90% of the recommended FDA label dose.

Results Among 166 patients treated with CAR T-cell therapy there were 17 (10.2%) patients with baseline RI and 149 (89.8%) without RI. After CAR T-cell infusion, the incidence of any grade AKI was not significantly different between patients with baseline RI compared to those without RI (42% vs. 21% p=0.08). Similarly, severe grade 2/3 AKIs were seen in 1/17 (5.8%) with baseline RI and 11/149 (7.3%) without RI (p=1). Decreased renal perfusion (28/39, 72%) was the most common cause of AKI with cytokine release syndrome (CRS) contributing to 17/39 AKIs (44%). Progression-free-survival (PFS) and overall survival (OS) did not differ between patients with or without RI or between those with standard-dosed or dose-reduced fludarabine. By contrast, patients experiencing AKI had worse clinical outcomes than those without AKI (multivariable PFS HR 2.1, 95%CI 1.2-3.7; OS HR 3.9, 95%CI 2.1-7.4). Notably, peak inflammatory cytokine levels were higher in patients who experienced AKI. Finally, we describe two patients with end-stage renal disease (ESRD) on dialysis who received lymphodepletion and CAR T-cell therapy.

Conclusion Baseline renal function did not affect renal or efficacy outcomes after CAR T-cell therapy in DLBCL. On the other hand, patients with AKIs went on to experience worse clinical outcomes. AKIs were commonly related to CRS and high peak inflammatory cytokine levels. CAR T-cell therapy is feasible in ESRD patients and requires careful planning of lymphodepletion.


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